Document XRqYoX0mvYxZNM88K8VJ8qr3w

Description Memo from Ford to Christofano re: Samples for acute oral toxicity studies. Exhibit #P0503 PIN # Date Author Addressee 01450-1 28-Jul-66 JOHN P FRAWLEY OETTEL & DIELEMAN, RIEN PHILLIPS, R.C. & CHRISTOFANO, TAVES, N.A. & 3 OTHERS E.E. Description Cover letter from Frawley to Oettel for samples sent to BASF for analysis of dioxin content as discussed in September of 1965. Exhibit #P0508 PIN # Date Author Addressee Description 06346-51 23-Aug-66 J A NOONE HERCULES EMPLOYEES Minutes of NACA meeting on August 23, 1966. Exhibit #P0509 PIN # Date Author Addressee Description 06339-44 23-Aug-66 C L DUNN FILE Handwritten notes of Dunn of NACA meeting of August 23, 1966. Exhibit #P0510 PIN # Date Author Addressee 01246 29-37 26-Aug-66 R DIELEMAN FRAWLEY, J.P. & PHILLIPS, H.C. Description Letter from Diehlman to Frawley reports on visit of Oettel at BASF and attaches the 1955 report by Oettel re: 1953 exposure; report has evidence compelling punitive IV. A. 170 1552S damages: no summary possible. Exhibit #P0511 PIN # Date Author Addressee Description 13970-86 01-Sep-66 HERCULES CORP GOVERNMENT Contract between Government and Hercules, Inc. (DSA-400-67-C-1633), effective date September 1, 1966,. 437,000 gal. AO for $2,923,530 from 10/1/66 to 6/1/67; free from defects. Exhibit #P0516 PIN # Date Author Addressee Description 06362-5 27-Sep-66 C L DUNN FILE Minutes of NACA meeting of 09/27/66. Exhibit #P0517 PIN # Date Author Addressee Description 01985-6 01-Oct-66 HERCULES CORP HERCULES Dechlorination Manual - "CAUTION!I! Do not let temperature get above 170 degrees and do not let pressure get above 315 pounds." Exhibit #P0525 PIN # Date Author Addressee 00000 19-Oct-66 JOHN P FRAWLEY OETTEL & SCOTT, R.B. PHILLIPS, R .C. & DIELEMAN, TAVES, M.A. & FORD, J.J. R. Description Letter from Frawley to Oettel of BASF re: bioassay for dioxin and Hercules rejecting new efforts to determine a new method; (Dow) reports positive results with samples of 2,4,5-T acid containing 1 ppm dioxin. 155 IV. A. 171 Exhibit #P0526 PIN # Date Author Addressee Description 06366-70 25-Oct-66 C L DUNN Minutes of NACA meeting on October 25, 1966. Exhibit #P0527 PIN # Date Author Addressee Description 06366-70 25-Oct-66 C L DUNN Handwritten notes of Dunn on NACA meeting of October 25, 1966. Exhibit #P0532 PIN # Date Author Addressee Description 31639-50 03-Nov-66 BIOTEST LABORATORIES HERCULES Biotest Laboratories report to Hercules, Inc. on acute oral toxicity studies on three materials. Exhibit #P0534 PIN # Date Author Addressee Description 00000 04-Nov-66 INC HERCULES Esterification manual; essential materials formulas. Exhibit #P0563 PIN # Date Author Addressee 06399-401 18-Jan-67 C L DUNN IV. A. 172 15524 Description Minutes of NACA meeting of January 18, 1967. Exhibit #P0567 PIN # Date Author Addressee 15034-44 27-Jan-67 K WILDER EAGAN, J. & GIVENS, K.T. Description Memo from Wilder to Eagan re: visit to U.S. Army phosphate development works, Muscle Shaols, Alabama; describes usage in V N , 2-4 applications, 30 days apart. Exhibit #P0587 PIN # Date Author Addressee 17060-1 23-Feb-67 K T GIVENS TRAUB, JOHN L. & COPELAN, J.G. EAGAN, J.M. & YATES, R.T. RENO, P.J. & 2 OTHERS Description Letter from Givens to Traube re: Hercules' proposal of building a new plant. Exhibit #P0601 PIN # Date Author Addressee Description 08406-10 28-Mar-67 G E LYNN US DA Lynn speech to USDA re: collect data on toxicity pertinent to use of phenoxy herbicides. Exhibit #P0604 PIN # Date Author Addressee Description 01247 29-Mar-67 P OETTEL FRAWLEY, JOHN P. Letter from Oettel to Frawley re: photographs of people with acne. IV. A. 173 15525 Exhibit #P0607 PIN # Date Author Addressee 017052-4 03-Apr-67 K T GIVENS YATES, R.T. & RENO, P.J. EAGAN, J.M. & HILLER, J. COPELAN, J.G. & 4 OTHERS Description Letter from Givens re: Orange Production, Edgewood Arsenal. Exhibit #P0612 PIN # Date Author Addressee Description 06411-15 20-Apr-67 C L DUNN Minutes of NACA meeting of April 20, 1967. Exhibit #P0619 PIN # Date Author Addressee Description 06422-3 11-May-67 G E LYNN HAZLETON LAB. Letter from Lynn to Hazleton Lab., Inc. re: verbal arrangement of 04/20/67 between Lynn and Hazleton to prepare petitions for negligible tolerances for use on crops for phenoxy herbicides. Exhibit #P0620 PIN # Date Author Addressee Description 06420-1 12-May-67 G E LYNN MEMBERS NACA & NOONE, J.A. HALEY, DENIS Memo from Lynn re: NACA and Hazleton meeting of May 11, 1967. Exhibit #P0630 IV. A. 174 1552S PIN # Date Author Addressee 32493-4 08-Jun-67 EMIL E CHRISTOFANO FANCHER, OTIS & SIDWELL, A.E. DUNN, C.L. & SCOTT, R . B . Description Letter from Christofano to Fancher re: Hercules Project No. 67-13; liver damage studies; toxicity of three materials to rabbits. Exhibit #P0635 PIN # Date Author Addressee 03904-5 . 29-Jun-67 JOHN P FRAWLEY OETTEL, PROF. H. & DIELEMAN, R. PHILLIPS, H.C. & SCOTT, R.B. DUNN, C.L. & SIDWELL, A.E. Description Letter from Frawley to Oettel re: Columbian study. "I agree with you that this report is very disturbing." States that 2,4,5-T acid and ester are significantly more toxic than TCP. Exhibit #P0638 PIN # Date Author Addressee 32452-62 30-Jun-67 J M EAGAN WILDER, H. E . & FRAWLEY, J.P. Description Memo from Eagan to Wilder re: chloracne cases in Columbia, South America. Exhibit #P0640 PIN # Date Author Addressee Description 14692-704 06-Jul-67 C W CARTY HERCULES Letter from Carty to Hercules Powder Co., Inc. demonstrates private industry's input in reviewing commentary and affecting redrafting of government specs, at government's request. 15527 IV. A. 175 Exhibit #P0641 PIN # Date Author Addressee Description 15600-13 11-JuI-67 W W RAYNOLDS WILDER, H.E. Memo re: July 6, 1967 letter of Carty's to Hercules Powder Co., Inc. Exhibit #P0644 PIN # Date Author Addressee Description 32149 18-Jul-67 MITCHELL R ZAVON CHRISTOFANO, E.E. Letter of Zavon to Christofano re: his request for a meeting regarding comparative industry study of employees. Exhibit #P0646 PIN # Date Author Addressee Description 32148 28-Jul-67 EMIL E CHRISTOFANO ZAVON, M. & EAGAN, J.M. SIDWELL, R. Letter from Christofano to Zavon rejecting proposed study. Exhibit #P0649 PIN # Date Author Addressee Description 15392-94 11-Aug-67 A E SIDWELL EAGAN, J.M. & SCOTT, R. WILDER Memo from Sidwell to Eagan re: "Orange quality problem - recites that Hercules has produced nearly 15,000,000 pounds of Agent Orange since November 15, 1964. Exhibit #P0650 PIN # 06436-7 IV. A. 176 15528 Date Author Addressee Description 17-Aug-67 G E LYNN NACA MEMBERS Memo from Lynn to Members of Industry Task Force on Phenoxy Herbicide Tolerances re: 2,4,5-T formulations. Exhibit #P0653 PIN # Date Author Addressee Description 31918 28-Aug-67 A E SIDWELL Appropriation Request signed by A.E. Sidwell re: infrared spectrophotometer. Exhibit #P0657 PIN # Date Author Addressee Description 15468-9 02-Sep-67 A L TREISBACK WILDER Handwritten notes from Treisback to Wilder re: "quality, purity, and chemistry of our operation." Exhibit /P0660 PIN # Date Author Addressee 15454-6 05-Sep-67 M A TAVES EAGAN, J.M. & RENO, P.J. TURK, E. & SCOTT, R. B . GIVENS, K.T. & 3 OTHERS Description Memo from Taves to Eagan re: "Orange" Analysis; Govt, does not know components in products which are known to Hercules; before advising Govt., Hercules will study. Exhibit #P0663 PIN # Date Author 15443-6 0 7 -Sep-67 R B SCOTT 15529 Addressee TAVES, M.A. & CLARK, W.H. GIVENS, K.T. & EAGAN, J.M. TURK, E. & 2 OTHERS Description Memo from Scott to Taves re: Orange; testing September 5, 1967. Exhibit #P0664 PIN # Date Author Addressee 15449-50 07-Sep-67 E T GIVENS EAGAN, J.M. & YATES, R.T. RENO, F.J. & 3 OTHERS Description Memo from Givens to Eagan re: NACA's proposed guidelines. Exhibit #P0666 PIN # Date Author Addressee Description 15903-4 101 12-Sep-67 J M EAGAN Notes of Eagan re: Synthetics Dept. Proposed Meeting, etc. Exhibit #P0669 PIN # Date Author Addressee Description 14716 19-Sep-67 UNKNOWN Notes. Exhibit #P0671 PIN # Date Author Addressee 13903-4 26-Sep-67 K T GIVENS EAGAN, J.M. & SCOTT COPELAND, J.G. & TURK, YATES & 2 OTHERS E. Description MEMO RE: "ORANGE QUALITY" 1553Q Exhibit #P0677 PIN # Date Author Addressee 32150 1O-Oct-67 E E CHRISTOFANO DUNN, C.L. & EAGAN, J.W. WILDER, H.E. & SIDWELL, A.E. Description Memo from Christofano to Dunn re: Dr. Zavon at Kettering Lab doing a prospective study of 15 - 20 year duration. Exhibit #P0683 PIN # Date Author Addressee Description 06475-9 17-Oct-67 C L DUNN Minutes of meeting of October 17, 1967 NACA Exhibit #P0685 PIN # Date Author Addressee 02986PLUS 25-Oct-67 R B SCOTT VANDOVENIER, W. & COPELAND, J.C. CRITTENDEN, K.D. & EAGAN, J.M. GIVENS, K.T. & 2 OTHERS Description Letter from Scott to Vandovenier and copy of proposed specifications for herbicide Orange; cover letter for 10/24, proposed specs as drafted by Hercules. Exhibit #P0698 PIN # Date Author Addressee Description 06549 27-Nov-67 C L DUNN MEMBERS NACA Letter from Dunn to members of NACA re: conference with USDA. 1553 - Exhibit #P0699 PIN # Date Author Addressee 06547-8 27-Nov-67 C L DUNN HAYS, HARRY & IRVING, ARS ANDERSON, USDA & DANIELSON, ARS Description Letter from Dunn to Hays requesting Extension for 1 year beyond 12/31/67 for cancellation date at registrations of 2,4-D and 2,4,5-T and others. Exhibit #P0702 PIN # Date Author Addressee 06554-56 08-Dec-67 C L DUNN FDA & USDA Description Letter from Dunn to FDA on behalf of NACA Industry Task Force on phenoxy herbicide tolerance. Exhibit #P0703 PIN # Date Author Addressee 06580-1 12-Dec-67 C L DUNN FDA & USDA Description Letter from Dunn to FDA similar to letter of 12/8/67. Exhibit #P0708 PIN * Date Author Addressee Description 15514 27-Dec-67 A E SIDWELL LOWE, L.E. Memo from Sidwell to Lowe re: unknown, still at 8.5%. Factor "X" Exhibit #P0710 PIN # 06584 1553? Date Author Addressee Description 29-Dec-67 HAROLD G ALFORD HERCULES Letter from Alford at USDA to Dunn at Hercules re: 11/27 request granted until 1/1/69. Exhibit #P0715 PIN # Date Author Addressee & SCOTT, 14671-8 02-Jan-68 K T GIVENS WILDER & K.E. CRITTENDEN, E.D. EAGAN, J.M. R.B. & RENO, P.J. Description Memo from Given to Wilder re: New contract - Herbicide Orange; Hercules participation in reviewing and redrafting proposed government specs with portions of contract attached. Exhibit #P0716 PIN # Date Author Addressee Description 06592-98 04-Jan-68 UNKNOWN Minutes of meeting of NACA meeting of January 4, 1968. Exhibit #P0718 PIN # Date Author Addressee 14664-70 1O-Jan-68 A E SIDWELL EAGAN, J.M. Sc CRITTENDEN, GIVENS, K. T . Sc RENO, D.J. SCOTT Sc WILDER E.D. Description Memo from Sidwell to Eagan re: "New Contract, Orange" detailing critiques and suggested changes - "you will remember that we have the unsolved problem of compound 'x'' in the butyl and ester. . ." 15533 a Exhibit #P0721 PIN # Date Author Addressee 15478-9 11-Jan-68 K T GIVENS WILDER, H.E. EAGAN, J.M. & CRITTENDEN, & RENO, P.J. E.D. Description Memo and attachment from Givens to Wilder re: use of imported 2,4,5-T; refers to authority to use imported 2,4,5-T for Agent Orange production. Exhibit #P0724 PIN # Date Author Addressee 17041 20-Jan-68 A E SIDWELL TAVES, M.A. & EAGAN, J.M. SCOTT, R.B. & WILDER, H.E. FISHER, J.R. & TECH. FILE Description Memo re: Compound "X" in Production n-Butyl-T. Exhibit #P0727 PIN # Date Author Addressee Description 15474-6 25-Jan-68 K T GIVENS COLLNS, G.F. & CRITTENDEN, E.D. EAGAN, J. & SCOTT, K. WILDER, N.E. Letter from Givens to Collins demonstrating Hercules' role in preparation and drafting of specs. Exhibit #P0730 PIN # Date Author Addressee Description 17050 29-Jan-68 K T GIVENS WILDER Memo from Givens to Wilder re: Herbicide Samples; use of foreign 2,4,5-T acids. IV. A. 182 15534 Exhibit #P0731 PIN # Date Author Addressee 15400 29-Jan-68 A L TREISBECK GIVENS, K. T . & EAGAN, J.W. SCOTT, R.B. & SIDWELL, A.E. Description Memo re: Orange Analyses; Contract DSA-400-67-C-8314; changing specs. Exhibit #P0739 PIN # Date Author Addressee Description 13706 20-Feb-68 R W HUSTON TREISBACK, A.L. Note from Huston to Treisback re: being below specs. Exhibit #P0748 PIN # Date Author Addressee Description 15344-55 27-Feb-68 GEORGE F COLLINS HERCULES POWDER Letter from Collins of Defense Supply to Hercules; enclosing copies of a review purchase description for herbicide qrange; requesting Hercules' comments. Exhibit #P0749 PIN # Date Author Addressee Description 06669 29-Feb-68 CHIPMAN BALES MCCOLLISER, RON Letter from Bales at Chipman Chemical Co. to McCollister re: subacute toxicity data requested by FDA. Exhibit #P0753 PIN # Date 15343-53 04-Mar-68 IV. A. 183 15535 Author Addressee K T GIVENS SCOTT, R. Sc TREISBACK, A.L. Description Memo from Givens to Scott and Treisback re: demonstrating Govt's acceptance of Hercules' changes in specs. Exhibit #P07 54 PIN # Date Author Addressee 06670 04-Mar-68 C L DUNN BAKER & HEW Description Letter from Dunn to Baker at HEW re: Pesticide Petition 8F0676 for negligible residues of the herbicide. Exhibit #P0759 PIN # Date Author Addressee Description 06691-2 08-Apr-68 HEW BAKER DUNN, C.L. & ARS US DA Letter from Baker at HEW to Dunn re: Hercules' inability to establish tolerances as requested; Hercules may amend or withdraw petition. Exhibit #P0761 PIN # Date Author Addressee Description 06701 15-Apr-68 C L DUNN NACA MEMBERS Sc KRAUSCHE, K CANKIN, R.A. Memo from Dunn to NACA members re: 2,4,5-T petition; re: 4/8/68 letter. Exhibit #P0762 PIN # Date Author Addressee 06700 15-Apr-68 C L DUNN BAKER, HEW Sc MCCOLLISTER, D.D. IV. A. 184 15536 BALES, I.W. & KRAUSCHE, K. HOLSING, G. CARL & NACA Description Letter from Dunn to Baker at HEW request NACA's pesticide petitions for negligible residue of herbicide MCPA be withdrawn without prejudice. Exhibit #P0765 PIN # Date Author Addressee Description 15389 0 9 -May-68 A L TREISBACK EAGAN, J.W. & GIVENS, K.T. SCOTT, R.B. & SIDWELL, A.E. BENNETT, T. Memo from Treisback to Eagan re: Recovered Acids - Addenda; government rewriting specs as requested by Hercules. Exhibit #P0766 PIN # Date Author Addressee Description 15342 09-May-68 GOVT GIVENS, K.T. Teletype message from Government on Hercules letterhead for Givens re: changes in tolerances (for percentage of 2,4-D and 2,4,5-T in Agent Orange); 810,000 gal. @ 7.25 per gal. for $5,872,500 offer; delivery at 90,000 gal. per month from 6/68-2/69. Exhibit #P0767 PIN # Date Author Addressee Description 15390-4 09-May-68 A L TREISBACK EAGAN, J. & GIVENS, E. SCOTT, R. & SIDWELL, A. BENNETT, T. Memo from Treisback to Eagan re: Recovered Acids; Orange quality problems and reference to attached letter of August 11, 1967. IV. A. 185 15537 Exhibit #P0768 PIN # Date Author Addressee Description 15395 09-May-68 A L TREISBACK GIVENS & EAGAN, J. BENNET, T. Memo from Treisback to Givens re: Orange; imported 2,4,5-T. Exhibit #P0774 PIN # Date Author Addressee 15288-319 05-Jun-68 K T GIVENS TREISBACK, A.L. & CRITTENDEN, EAGAN, J.M. & RENO, P.J. E.D. Description Memo from Givens to Treisback re: "Orange" Contract; attached new contract; 90,000 gal. per month from 6/30/68-2/28/69 for $5,872,500; free from defects; attached copies of 2/23/68 specs and amendment of 4/11/68. Exhibit #P0776 PIN # Date 13664 11-Jun-68 Author Addressee Description A S SIDWELL TREISBACK, A.L. Memo from Sidwell to Treisback re: Conference on Contract DSA-400-68-C-6093; conference with government. Exhibit #P0778 PIN # Date Author Addressee 13662-3 12-Jun-68 K W HUSTON TREISBACK, A.L. & BUMP, BENNETT, T. & RAY, F.H. PENNOCK, J.G. & FISHER, R.A. J.R. Description Memo from Huston to Hercules employees re: DSA Contract DSA-400-68-C-6093; meeting IV. A. 186 15538 with government to discuss, and agree on contract. Exhibit #P0799 PIN # Date Author Addressee 15245 18-Sep-68 R W HUSTON BUMP, R.A. & PAMRY, S.A. GIVENS, K .T. & TREISBACK, SIDWELL, A.E. & 2 OTHERS A.L. Description Memo from Huston to Bump re: Documents "Orange" Contract. Exhibit #P0808 PIN # Date Author Addressee Description 04030-1 16-Oct-68 EMIL E CHRISTOFANO ROWE, V.K. Letter from Christofano to Rowe re: bioassay methods inconsistant and usefulness as a test for dioxin is questionable. Exhibit #P0816 PIN # Date Author Addressee Description 18121 O8-N0V-68 TREGLIA HERCULES Memo from Treglia at Dept, of Army to Hercules re: invitation to comment on proposed specs - suggestions that may result in a savings to Govt. Exhibit #P0818 PIN # Date Author Addressee Description 06888 03-Dec-68 ALFORD DUNN, C.L. Letter from Alford at USDA to Dunn re: Extension of Registrations for 2,4,5-T acid; Dunn's letter of 10/29/68; extend IV. A. 187 15539 date for finite tolerances to 1/1/70 Exhibit #P0824 PIN t Date Author Addressee 25992-4 30-Dec-68 J CHRISTOFANO DUNN, C.L. & OTHERS Description Memo from Christofano to Dunn re: Dioxin studies; biotest lab report on dioxin studies; studies inconsistent and inconclusive. Exhibit #P0870 PIN # Date Author Addressee Description DOW754889 25-NOV-69 J E JOHNSON Page two of Johnson report. Exhibit #P0890 PIN # Date Author Addressee Description 01540-2 16-Jan-70 J J FORD TAVES, M.A. & SCOTT, R.B. DUNN, CL.L & WALKER, J. CONNER, A. Memo from Ford to Taves re: analysis of 2,4,5-T Acid for "Dioxin" Content; further development indicated; 4-6 weeks to evaluate proposed modifications. Exhibit #P0911 PIN # Date Author Addressee Description 26964 24-Feb-70 J P FRAWLEY Notes of Frawley re: findings of cleft palate. 15540 IV. A. 188 Exhibit #P0923 PIN # Date Author Addressee 01588-9 19-Mar-70 J J FORD TAVES, M.A. & SCOTT, R.B. DUNN, C.L. & WALKER, J.F. CONNER, A.Z. & SIDWELL, A.E. Description Memo from Ford to Taves re: Analysis of 2,4,5-T Acid for "Dioxin" Content; retesting of old samples produced in 1965; attached chart shows dioxin content as high as 3.5 ppm in 1965. Exhibit #P0938 PIN # Date Author Addressee Description 03877 10-Apr-70 J G COPELAND Synthetics Dept. R&D Newsletter of Copeland; " . . . dioxin, which is highly toxic, a severe skin irritant, and a suspected teratogen." Exhibit #P0942 PIN # Date Author Addressee 04032 15-Apr-70 R B SCOTT DUNN, C.L. & PIERCE, H.F. LEMONS, E.W. & GIVENS, K.T. FRAWLEY, J.P. & 2 OTHERS Description Memo from Scott to Dunn reL: 2,4,5-T Analyses. Exhibit #P0959 PIN # Date Author Addressee 04034-5 10-Jun-70 JOHN J FORD PETERSON, R. & KOPKINS SCOTT, R. & TAVES, M.A. Description Memo from Ford to Peterson re: Separation of the Toxic Contaminant 2,3,7,8-TCP from 15541 IV. A. 189 2,4,5-TCP acid; dioxin is a highly toxic contaminant; teratogenic effects recently attributed to 2,4,5-T may be due to dioxin contaminant. Exhibit #P0980 PIN # Date Author Addressee Description 27817-18 23-Nov-70 JOHN P FRAWLEY HIGGIN, JOHN C. Memo from Frawley to Higgin discussion whether teratology was associated with dioxin; government agency sponsoring study not familiar with toxicity of dioxin; Surgeon General declared 2,4,5-T hazard to health; 2,4,5-T banned. Exhibit #P0981 PIN # Date Author Addressee Description 27349 24-Nov-70 J P FRAWLEY DUNN, C.L. Memo from Frawley to Dunn re: completed Bionetics study on 2,4,5-T. Exhibit #P0993 PIN # Date Author Addressee Description 27396-402 26-Jan-71 JOHN P FRAWLEY WILSON Letter from Frawley to Wilson, Advisory Committee on 2,4,5-T; lack of hazard presented; Hercules acknowledges past history of U.S. and Germany. Exhibit #P0994 PIN * Date Author Addressee 27462 17-Feb-71 J P FRAWLEY DUNN, C.L. & COPELAND, PIERCE, H.F. & GIVENS, OTHERS J.G. K.T. IV. A. 190 15542 Description Memo from Frawley to Dunn re: Dosing Error in Bionetics Study on 2,4,5-T; mistake in bionetics report and what they should do. Exhibit *P0999 PIN # Date Author Addressee 27656 30-Mar-71 JOHN P FRAWLEY WILSON, JAMES G. & MEMBERS ADVISORY COMMITTEE & ON 2,4,5-T Description Letter from Frawley to Wilson on Advisory Committee on 2,4,5-T suggesting the restriction of dioxin content . . to a safe level." Exhibit #P1006 PIN # Date Author Addressee Description 03579 01-Jun-71 GEORGE H HOPKINS SIDWELL, A.E. & FORD, J.J. SCOTT & GIVENS, K.T. DUNN, C.L. Memo from Hopkins to Sidwell and Ford re: Removal of "Dioxin" from Silvex and removal of "Dioxin" from 2,4,5-T; patent in removal process. Exhibit #P1007 PIN # Date Author Addressee 03576-8 03-Jun-71 A E SIDWELL HOPKINS, GEORGE H. & SCOTT, GIVENS, K.T. & DUNN, C.L. TREISBACK, A.L. & 2 OTHERS R.B. Description Memo from Sidwell to Hopkins re : Removal of "Dioxin" from Silvex. Exhibit #P1011 PIN # Date 27741 29-Jul-71 IV. A. 191 15543 Author Addressee Description R STEHL DOW Analytical Laboratories report of July 29, 1971; 4/4/71 sample tested and Hercules rated it 0.18 ppm and Dow rated it less than 5 ppb. Exhibit #P1015 PIN # Date Author Addressee Description 27788-9 28-Oct-71 D D MCCOLLISTER WEIR, ROBERT J. Letter from McCollister to Weir re: importance of not publishing difference and how to describe difference of 0.18 ppm v. 0.005 ppm. Exhibit #P1021 PIN # Date Author Addressee Description 01740 15-Nov-71 W C KENYON TAVES, M.A. & HALL, R.T. FORD, J.J. Memo from Kenyon and Shearer to Taves re: reports of Dow on 2,4,5-T from Hercules; attempted explanation. Exhibit #P1029 PIN # Date Author Addressee Description 01754-5 17-Jan-72 D D MCCOLLISTER HART, E. ROSS Deposition of A.E. 18, 1980; Sidwell taken on April Exhibit #P1089 PIN # Date Author Addressee Description 00000 28-Apr-80 UNKNOWN Trial testimony of A.E. Sidwell. 15544 Exhibit #P1105 PIN # 00000 Date 02-May-83 Author UNKNOWN Addressee Description Affidavit of Charles L. Dunn date 05/02/83. 15545' "7 Exhibit #P0025 PIN # Date Author Addressee DS00017892 F R KENNEDY SAVAGE & CORT Description Memorandum dated March 20 [year illegible] from F. R. Kennedy to S. Savage, New York Sales, stating that the suspect batch samples from the suspect batches have been segregated and put aside for safekeeping. He also reports that Dr. Bleiberg said that he had been contacted, had asked for follow-up materials, and had not done anything more when these materials (photographs of the affected personnel) were not forthcoming. Exhibit #P0026 PIN # Date Author Addressee Description DS00001061 F GORDON STEWARD Staff memorandum of unclear date from F. Gordon Steward reporting on technical operations for the month of April, 1967. The report notes that the use of porosities to filter dioxins was not very encouraging, but that the carbon filter seemed to be effective. Plugging seemed to be a continuing problem. Exhibit JP0027 PIN # Date Author Addressee Description DS 22713 UNKNOWN SCRATCH PAD NOTES REGARDING LETTER OF 10/9/64. Exhibit #P0028 PIN # Date Author Addressee 24673 UNKNOWN * IV. A. 194 15546 Description OPERATING COMMENTS PLANT TECHNICAL JUNE, 1969. Exhibit *P0029 PIN # Date Author Addressee Description 27928 PAUL GROSS, MD DIAMOND ALKALI CO JANUARY, 1960, SEVENTH REPORT ON EVALUATION OF CHLORACNE. Exhibit #P0074 PIN # Date Author Addressee DS00022493 290655 J M YORK SCOVILLE & INGLEY BURTON & KIRP Description Memorandum dated June 29, 1955 from J. M. York, MD, to L. P. Scoville concerning chloracne at the Newark plant. Recites visit by the author to the plant, where fumes were noxious but of unknown toxicity. Describes chloracne and its mechanisms, stating that there is really no cure, and further stating that a case has to be seen to appreciate how socially debilitating it can be. Recommends sending some of the worst cases to a Dr. Marion B. Sulzberger in New York city, but further recommends that this be deferred until the plant is cleaned up or it will be an illusory remedy. Also recommends that better physical examinations be given to employees so that blood and liver damage can be assessed. Exhibit #P0080 PIN # Date Author Addressee DS00008854 30-Aug-55 GEORGE H BURRIS ROSENFELD & BURTON FROWNE & PORTER TOWLE & OTHERS Description Technical Memorandum dated August 30, 1955, from G. H. Burris and M. Rosenfeld to Mr. 15547 IV. A. 195 J. Burton describing the methods used to establish absorption curves to identify the impurities in 2,4,5-T by means of chromotography. Suggests that the curve is close to the curve established for dichlorosorcinol, but allows that a polychlorinated diphenyl ether compound may also be indicated in small amounts. Exhibit #P0081 PIN # Date Author Addressee Description DS00024253 23-Sep-55 J BURTON GLEISSNER & BROWNE TOWLE Memorandum dated September 23, 1955, from J. Burton to Dr. B. D. Gleissner reporting on toxicology tests run on rabbits by the Industrial Toxicological Laboratories. The tests on crude TCP showed that reactions to the August production samples existed but were less serious than reactions to May production samples. This indicated that they were on the right track in lower autoclave temperatures, according to the author, but that that alone would not solve the problem. Exhibit #P0093 PIN # Date Author Addressee Description DS00019554 20-Oct-56 JACOB BLEIBERG J BURTON Letter dated October 20, 1956, from Dr. Jacob Bleiberg to Mr. J. Burton summarizing his recommendations concerning chloracne at the Newark plant. He notes that the probable chloracnogen is a chlorinated di-phenyl. For Prophylaxis purposes, he recommends cleanliness and special soaps. For treatment he recommends using creams, but suggests looking for systemic disorders as well. The report contains numerous recommendations concerning diet, etc. 15548 IV. A. 196 Exhibit #P010 PIN # Date Author Addressee DS00008217 21-Jun-57 J BURTON GUIDI & BROWNE Description Memorandum dated June 21, 1957, from J. Burton to R. Guidi and referenced to a file, 2,4,5-TCP Process Development. Memo outlines the need to double TCP production and to eliminate chloracne impurities. Also wants to run at a lower pressure as a safety matter. Explores various suggestions for accomplishing these objectives from an engineering point of view. Exhibit #P0103 PIN # Date Author Addressee DS00017415 18-Sep-57 D J PORTER BURTON & LUKES SUTTER & CLEVELAND Description Memorandum dated September 18, 1957 from D. J. Porter at Painesville to J. Burton at Newark reporting on meeting with Dr. Kudesus of Boehringer to discuss acquisition of know-how for production of penta- chlorophenol. Told Kudesus that since the work of A1 Hirsch and Irving Rosen "several years ago" and the more recent work of Jack Jenney and Al Lewis, they had no indication of chloracne trouble. Dr. Kudesus said he would send them a copy of his report on the problem which had caused them to shut down one of their plants and, in the meantime, he identified the culprit with a diagram which is reported in the memorandum. It was said that the material is not formed if the triTCP autoclave temperature is kept below 155 degrees C, and if the caustic mixture is not more than 120 C. Writer suggests trying this in the TCP plant in view of the problems there. Exhibit #P0105 PIN # DS00022024 IV. A. 197 Date Author Addressee Description 11-Oct-57 D J PORTER GUIDI & BURTON LUKEE Memorandum dated October 11, 1957 from D. J. Porter to R. A. Guidi reporting the forwarding of a transalation of a memo from C. H. Boehringer Sohn, Ingelheim, reiterating comments previously made "some time back" by Dr. Kudesus of Boehringer. Cover letter suggests that if there are problems running a syline at Newark, a test could be done at the autoclave at Painesville. The attachment advises of the steps in the reaction where acnegen can be seen to be formed, and of the further steps (principally temperature control) that can be used to minimize that risk. Exhibit #P0106 PIN # Date Author Addressee Description DS 27915 19-Dec-57 MARIAN L WESTRICK, PHD J. BURTON SIXTH REPORT ON EVALUATION OF CHLORACNE NOV 1957 Exhibit #P0115 PIN # Date Author Addressee 000000 19-Sep-58 DONALD M PURDY DIAMOND ALKALI & MANK EDWARD Description Agreement dated September 10, 1958 by employee, Donald M. Purdy, to assign any patent for work done for Diamond to Diamond. Exhibit #P0128 PIN # Date Author Addressee DS00017413 30-Sep-59 THORNTON HOLDER BURTON & BRUMBAUGH BORROR & EVERSON PORTER & GOYB IV. A. 198 15550 Description Internal Diamond Memorandum dated September 30, 1959 reporting information from Boehringer that they had not had a chloracne case for several years by reason of changes in process and a major overhaul of their factory. The memo notes that Boehringer continued to have liver cases several years after clearing up their chloracne problems. Exhibit #P0137 PIN # Date Author Addressee DS00010807 20-May-60 THORNTON HOLDER SCOVILLE & HONOUR Description Memorandum dated May 20, 1960 from Thornton F. Holder to L. P. Scoville referring to differences in accidents at Newark and at Ingelheim and stating that he would be willing to use his offices to have a meeting with Boehringer (Cela) if that was des ireable. Exhibit #P0140 PIN # Date Author Addressee Description DS00008450 21-Jun-60 J BURTON BORROR & GUIDI LINDEMANN & SCOVILLE WEINER Confidential Memorandum dated*June 21, 1960 from J. Burton to J. A. Borror reporting on laboratory work concerning the 2,4,5-T process. The memo suggests that yields are satisfactory at a 2:2 mol ratio. Identifies information on Newark that chlorinated dyphenyl ethers are the probable cause of chloracne. Suggests that if lab results cannot be duplicated at the plant, then the recommendation is to increase the caustic ratio rather than the heat of reaction because higher temperatures promote chloracnegen (chlorinated diphenyl ethers) formation. The memo suggests that a dilutent might be used to moderate the reaction also. 15551 IV. A. 199 Exhibit #P0141 PIN # Date Author Addressee Description DS00022022 23-Jun-60 J J BURTON CONRAD & DELL CELA Copy of a letter dated June 23, 1960 from J.Burton to Herr. Conrad and Dell of Cela describing in some detail Diamond's process, experience, their attempts to understand how to avoid future explosions and their request for a similar exchange of information from Cela. Exhibit #P0145 PIN # Date Author Addressee Description DS00021951 10-Aug-60 NONE BOEHRINGER SOHN BORROY Letter from illegible person at Boehringer Sohn to J. A. Borror, Diamond Alkali Company dated August 10, 1960 describing in detail their process [CELA] for processing TCP to avoid chloracnegens. Asks for confidential exchange of information on the subject. Refers to September 20, 1957 letter addressed to Plainsville, Ohio. Exhibit #P0161 PIN # Date Author Addressee DS00011518 06-Mar-62 R L ANNIS EVERSON & CROSS DUNNING & ENTEMANN HIRSCH & OTHERS Description Memorandum dated March 6, 1962 from R. L. Annis to H. E. Everson with a wide distribution list reporting on progress of 2,4-D and 2,4,5-T Process Studies. The studies look toward expansion of production outputs. The report states a revised 2,4-D process has been virtually completed, and that it is hoped that a 2,4,5-T process can 15552 IV. A. 200 be developed from chat process, but notes that this will require higher temperatures and higher pressures. The report is emphatic that the plant will require updating at some expense for the new processes. No mention is made of health considerations. Exhibit #P0166 PIN # Date Author Addressee 24256 11-May-62 W GOODLOE R. A. GUIDI & R. F. LINDEMANN Description UNSIGNED MEMO BY W.GOODLOE TO R. A. GUIDI DATED 11 MAY 1962 ADVISING ALL CHLORACNE SAMPLES (14) PREPARED AS REQUESTED & READY FOR SHIPMENT TO MELLON INSTITUTE. DESCRIPTION OF EACH SAMPLE ATTACHED. Exhibit #P0171 PIN # Date Author Addressee Description DS 27937 07-Jun-62 JAMES M MC NERNEY DR. GUIDI 8TH REPORT ON EVALUATION OF CHLORACNE. Exhibit #P0178 PIN # Date Author Addressee DS00017412 09-Jul-62 K L CHANDLER GUIDI & WEINER Description Memo dated July 9, 1962 from Chandler to Guidi reporting that Riverdale Chemical and Quaker City Tree had serious complaints aobout chloracne associated with Diamond's product and asking whether there is a likelihood that these incidents will recur. Exhibit #P0185 155 PIN # Date Author Addressee Description DS00019539 06-Nov-62 H C BAISALO HILL W C & BAISALO H C GUIDI R A Confidential Memorandum re Chloracne containing what appears to be the outline of a speech concerning the chloracne problem and which is dated November 6, 1962. Document is incomplete as we have it. Exhibit #P0186 PIN # Date Author Addressee DS0000715 1O-Nov-62 EUGENE BAK BRAUN & GOODLOE WEINER & GUIDI HILL & OTHERS Description Detailed report concerning existing processes for 2,4-D and 2,4,5-T and making recommendations for changing processes for economy. Report is prepared by Eugene Bak with the assistance of Daniel Braun and William Goodloe, and is signed by Hill and Guidi. Exhibit #P0193 PIN # Date Author Addressee Description DS00008832 07-Jan-63 RE LINDEMANN HILL Memorandum dated January 7, 1963 from R. F. Lindemann to W. E. Hill, Jr. reporting on his effort to identify the impurities in 2,4,5-T and TCP. States that the chromotograph of the impurity is close to the basic chemical, but with a slightly higher boiling point. Exhibit #P0201 PIN # Date Author DS00017405 15-Feb-63 R A GUIDI 15554 Addressee Description WEINER Memorandum dated February 15, 1963 from R. A. Guidi to H. S. Weiner re: forwarding an article given to him by Dr. Bleiberg suggesting the development of porphyria from the ingestion of hexachlorobenzene. Memo notes presence of porphyrins in urine samples collected from workers and at a level indicating liver disturbance. Says the article will set off the health authorities and that Bleiberg is already in contact with Dr. Birmingham for advice. Exhibit #P0206 PIN # Date Author Addressee DS00017400 25-Mar-63 H S WEINER GUIDI & WILKERSON Description Confidential Memorandum from H. S. Weiner to R. A. Guidi dated March 25, 1963 re: "Chloracne." The memo refers to a March 20 memo and states that USPH should not be allowed to visit the plant unless a full program concerning the visit is developed with Diamond's medical advisor and Marty Wilkerson. The memo suggests that thought be given to the possibility that the visit might be used as a sensational event in the news- papers. Exhibit #P0208 PIN # Date Author Addressee Description DS00024455 27-Mar-63 RICHARD W MCBURNEY JARVIS & BROWN OCIDI Memorandum dated March 27,1963 from Richard W. McBurney, M D , to Frank W. Jarvis in Cleveland. It notes the history with chloracne and states that recent articles have convinced Dr. Bleiberg that they may also be dealing with a liver problem. The letter states that the only way to begin to solve the problem was to renovate the old plant, subject to available financing. 15555 IV. A. 203 Exhibit #P0211 PIN # Date Author Addressee Description DS00017963 09-Apr-63 GUILLERMO CECIL Translation of a letter written in Spanish on April 9, 1963 by Leon R. Guillermo of Quimor to L. L. Cecil, Jr. re: "Problem in the Application of Weed Killers". The communication informs Mr. Cecil that workers in the Bucaramanga area have suffered severe reactions after using Diamond's 2,4-D and 2,4,5-T products. Exhibit #P0212 PIN # Date Author Addressee Description DS00019524 11-Apr-63 R A GUIDI WILKERSON & BROWN MCBURNEY Memo dated April 11, 1963 from R. A. Guidi to M. F. Wilkerson reporting on a visit of Drs. Key and Birmingham to Newark. Memo encloses a copy of a report from McBurney to Jarvis previously prepared. Guidi reports that two men are to be admitted to Beth Israel Hospital for further tests, "with specific emphasis on the kidneys and liver." Exhibit #P0222 PIN # Date Author Addressee DS00017940 02-May-63 R J MARRESE GUIDI R A & KING, J. 0. CHANDLER E. L. & L L CECIL Description Confidential Memorandum dated May 2, 1963 from R. J. Marrese to Larry L. Cecil arguing that the Quimor incident did not involve a product quality question as much as a personal hygiene factor. Exhibit #P0223 PIN # Date Author Addressee DS00017939 08-May-63 L L CECIL CLAGHORN & CREAMER KNOBLOCK & CLAIR Description Memorandum dated May 8, 1963 from L. L. Cecil to D. A . Claghorn, Herbicides, Columbia, forwarding materials for confidential consideration. Exhibit #P0227 PIN # Date Author Addressee Description DS00019506 20-May-63 JACOB BLEIBERG GUIDI & DIAMOND NEWARK Letter from Dr. Jacob Bleiberg to Guidi at Shamrock reporting findings of liver damage among plant workers in Newark. The letter suggests the source of the problem is the old factory building. Exhibit #P0229 PIN # Date Author Addressee Description DS00019523 31-May-63 R A GUIDI MC BURNEY & BROWN CORT MEMO OF FINAL HOSPITAL REPORT RE: 2 CASES Exhibit #P0230 PIN # Date Author Addressee Description DS00019518 07-Jun-63 R W MCBURNEY GUIDI & BROWN CORT Memorandum dated June 7, 1963 from Dr. McBurney to Mr. Guidi advising that workers affected by plant contamination no longer should be hospitalized since there is no treatment that can really help them, apart from removal from the contamination. Dr. McBurney opinions that the company's 1555 ? IV. A. 205 decision to renovate the old building will go far toward solving this problem. Exhibit #P0231 PIN # Date Author Addressee DS 19520 10-Jun-63 R A GUIDI DR. R. MC BURNEY & C.R. BROWN J. S. CORT, JR. & F. R. KENNEDY Description 1-0 MEMO SUBJECT CHLORACNE - MEDICAL REPTS ON AN UNK. Exhibit #P0247 PIN # Date Author Addressee Description DS00017393 14-Aug-63 R W MCBURNEY GUIDI & BROWN JARVIS Letter from Richard W. BcBurney MD dated August 14, 1963 to Raymond A. Guidi recommending a urine test for persons affected by chloracne. Exhibit #P0248 PIN # Date Author Addressee Description DS00017392 01-Oct-63 J CORT KENNEDY Memo from J. S. Cort, Jr. to F. R. Kennedy, dated October 1, 1963 asking if urine tests had been started. Exhibit #P0255 PIN # Date Author Addressee Description DS00017390 25-Nov-63 F R KENNEDY CORT Memorandum dated November 25, 1963 from F. R. Kennedy to J. S. Cort, Jr. in Cleveland sending a copy of the notice that was posted telling the employees they were all IV. A. 206 15558 going to be given urine checks. Exhibit #P0272 PIN # Date Author Addressee DS00019479 05-Mar-64 J S JR CORT MCBURNEY RICHARD & MASEK E J Description Memorandum dated March 5, 1964 from J.S. Cort, Jr. to Dr. Richard McBurney (cc. to Masek-legal) asking whether a purchaser of raw TCP should be warned of health hazards. Exhibit #P0273 PIN # Date Author Addressee DS00019480 06-Mar-64 RICHARD W MCBURNEY CORT & MASEK Description Internal Memorandum dated March 6, 1964 from Dr. Richard W. McBurney, M.D. to J. S. Cort, Jr., stating that TCP is a definite chloracne hazard to workers. It states that the customer may or may not be aware of this, and defers to the legal department (Mr. Masek) the issue of what duty there is to tell them.1, 11, but suggests that the obligation exists anyway. Responds to a memorandum of March 65, 1964 Exhibit #P0275 PIN # Date Author Addressee DS00017895 17-Mar-64 S B HONOUR QUIMOR LTDS & CORT GILES & PURDY Description Letter dated March March 17, 1964 from S. B. Honour to Guillermo Leon R. at Quimor acknowledging receipt of his letter of March 2d and saying that tests show that the samples of the product being ques tioned are identical to other batches of Diamond's product. Nonetheless, the letter 15559 IV. A. 207 says that the matter has been turned over to Diamond's insurance representative and that it has also agreed to take back all questioned product provided its drums are in marketable condition. Exhibit #P0276 PIN # Date Author Addressee DS00017893 18-Mar-64 LEX CREAMER DIAMOND ALKALI & NEW YORK Description Memorandum dated March 18, 1964 from Lex Creamer to "New York" reporting on 2,4,5-T outbreaks in Bucararaangea, Cali and Medellin, and describing the severity of those outbreaks. States that distributor, Quimor, is in joeopardy because of bad publicity. Exhibit #P0277 PIN # Date Author Addressee DS L7890 20-Mar-64 S B HONOUR JOHN BINGHAM, V P & QUIMOR LTDA Description LETTER RECOMMENDING BINGHAM ACT AS CONSULTANT & CONTACT DR. DIAZ. Exhibit #P0278 PIN # Date Author Addressee Description DS00017888 23-Mar-64 UNKNOWN CECIL Letter dated March 23, 1964 (incomplete) from Alexander & Alexander, insurance brokers, to Lawrence Cecil, Jr., Sales Manager, Agricultural Chemicals, Diamond Alkali Company, advising that American Foreign Insurance Association had given assurances to their Bogota representative that matters were in hand, and assuring Diamond that instructions had been given to keep the identity of the American manufacturer a secret. 15560 IV. A. 208 Exhibit #P0279 PIN # Date Author Addressee Description 17888 23-Mar-64 C W GILES LAWRENCE L. CECIL & D. M. PURDY DIAMOND ALKALI LETTER REGARDING DIAMOND'S PRODUCT LIAB. INSURANCE Exhibit #P0280 PIN # Date Author Addressee 19474 23-Mar-64 J S JR CORT J.A. FLOBECK & F.R. KENNEDY R. W. MC BURNEY & E. J. MASEK Description REGULATIONS RE HANDLING TRICHLOROPHENOL OR ITS SODIUM SALT. Exhibit #P0281 PIN # Date Author Addressee Description DS00017865 25-Mar-64 C W GILES CECIL LAWRENCE & PURDY D M DIAMOND ALKALI Letter dated March 25, 1964 from C. W. Giles, Asst. Vice President, Alexander & Alexander, to Lawrence L. Cecil, Jr., Sales Manager for Agricultural chemicals at Diamond Alkali reporting a request from American Foreign's Mr. George W. Arenas that the sample from "assurd's distributor" be tested by an independent laboratory. Exhibit #P0282 PIN # Date Author Addressee 117865 1S5 25-Mar-64 C W GILES LAWRENCE L. CECIL & SALES MANAGER AGRICULTURAL CHEM. & DIAMOND ALKALI IV. A. 209 Description SIGNED COPY OF LTR 3/25/64 RE PROD LIAB INS8 Exhibit #P0284 PIN # Date Author Addressee DS00017885 08-Apr-64 L L CECIL CORT & KENNEDY Description Confidential Memorandum dated April 8, 1964 from L. L. Cecil, Jr., to J. Cort in Cleveland and referring to Mr. Kennedy's letter of March 31. The Memo states that the Kennedy letter is possibly incorrect because no "formal" complaints were ever filed and investigated. States, however, that "we feel obligated" to tell you that Lex Creamer has advised "by way of conversation" that there are more problems, especially in El Salvador. Exhibit #P0285 PIN # Date Author Addressee DS17885Y 08-Apr-64 L L CECIL, JR J. CORT & F R KENNEDY Description UNSIGNED COPY OF MEMO DATED 4/8/64 BY CECIL TO CORT. Exhibit #P0287 PIN # Date Author Addressee Description DS00017881 20-Apr-64 L L CECIL QUIMOR LTDA & CORT ALEXANDER & A Letter dated April 20, 1964 from L. L. Cecil, Manager, Agricultural Chemicals, Quimor, Ltda. [Attn: Guillermo ] authorizing return of 1,725 gallons of weedkiller from Columbia and $907.12. Requests expedited handling. to 15562 IV. A. 210 Plaintiffs respectfully submit the following initial list of witnesses in conformity with paragraph IV.(B)(1) of the Magistrate's Pre-trial Order No. 17. Dr. Arthur W . Galston Eaton Professor of Botany, Department of Biology, New Haven, CN.: Dr. Galston is a plant physiologist; observed devastation of Vietnam; general causation; toxicity of tcdd to plants and humans; persistence of tcdd in ecosystem and bioaccumulation in human fatty tissue; Dr. Galston will also testify that there were other herbicides available in the 1960's that did not contain dioxin and could have defoliated the areas that 2,4,5-T was used to defoliate. See curriculum vitae, all summaries, with references and documents attached; deposition testimony in possession of all parties. Direct examination estimated 1 day; Cross examination estimated 1/2 day. Dr. Alastair W.M. Hay Department of Chemical Pathology, University of Leeds, Leeds, England: Dr. Hay is a biochemist and general lecturer; author of The Chemical Scythe, Lessons of ~ 2,4,5-! anil Dioxin, Disaster Research In Practice Series, 1982, Plenum Press, New York and London; generic causation on toxicity of tcdd to man; specific causation on toxicity to Vietnam veterans exposed to Agent Orange; observed devastation of Vietnam countryside; Dr. Hay will also testify that there were other herbicides available in the 1960's that did not contain dioxin and could have defoliated the areas that 2,4,5-T was used to defoliate. Dr. Hay will further testify that based upon his research and expertise, those who made the decisions with respect to the use of herbicides in Viet Nam were at the highest levels of Government, probably the Secretary of Defense and/or the 15563 V. A. 1 President. See curriculum vitae, all summaries, with references and documents attached; deposition testimony in . possession of all parties. Direct examination estimated 1-1 1/2 days; Cross examination estimated 1-1 1/2 days. Dr. Deborah Barsotti Professor of Toxicology, Philadelphia College of Pharmacy and Science, Philadelphia, PA.: Dr. Barsotti is a professor of toxicology; substantial personal research on halogenated aromatic hydrocarbons, including 2,3,7,8 tcdd or dioxin, and its teratological effects on animals and humans; general causation on toxicity, reproductive toxicity, fetotoxicity, gonadotoxicity, and embryotoxicity of tcdd; see curriculum vitae, all summaries, with references and documents attached; deposition testimony in possession of all parties. Direct examination estimated 3/4 day; Cross examination estimated 3/4 day. Dr. Ellen Silbergeld Chief Toxicologist, Environmental Defense Fund, Washington, D.C.: Dr. Silbergeld is an environmental scientist and toxicologist; chief toxicologist for the Environmental Defense Fund; Research scientist in Reproductive Toxicology for National Institute of Health; general causation expert on the extreme toxicity, neuro-toxicity, reproductive toxicity, and carcinogenicity of Agent Orange and tcdd; specific causation on the birth defects of Kerry Ryan, and Michael and Chad Jordan, as related to and caused by their respective fathers exposure to Agent Orange in Vietnam; see curriculum vitae, all summaries, with references and documents attached; deposition testimony in possession of all parties. Direct examination estimated 1 day; Cross examination estimated 1 day. Dr. Alan Scott Levin 450 Sutter, Suite 1138 Francisco, CA.: Dr. Levin medical doctor who has done considerable research on the immune system; San is a ;A V. A. 2 general causation expert on the extreme toxicity of tcdd and Agent Orange and its adverse health effects such as; chloracne, liver and systemic disorders; chemically induced immune disregulation; neurological disorders; reproductive disorders; and cancer; specific causation expert on the causal relationship of the various Agent orange/dioxin related adverse health effects upon the individual representative class plaintiffs themselves; see curriculum vitae, all summaries, with references and documents attached; deposition testimony in possession of all parties. Direct examination estimated 3/4 day; Cross examination estimated 1/2 day. Dr. Ronald Kerman Department of Surgery, University of Texas Medical School, "UTMS", 6431 Fannin, Houston, TX.: Dr. Kerman is Chief of Cellular Immunology at University of Texas Medical School at Houston; general causation expert on the extreme toxicity of tcdd and the immuno-toxicological effects on humans; see curriculum vitae, all summaries, with references and documents attached; deposition of Dr. Kerman has not been taken to date. Direct examination estimated 3/4 day; Cross examination estimated 1/2 d ay. Dr. Maureen Hatch Professor of Epidemiology, Columbia University, New York, NY.: Dr. Hatch is an epidemiologist at Columbia University; general causation regarding reproductive epidemiology and toxicology of Agent Orange and its dioxin, tcdd, and their specific applicability to miscarriages and congenital malformations (birth defects) in wives and children of Vietnam veterans; see curriculum vitae, all summaries, with references and documents attached; deposition testimony in possession of all parties. Directexaminat estimated 1 day; Cross examination estimated 1 day. Dr. Marvin Legator Professor of Environmental Toxicology, University of Texas Medical School, Galveston, TX.: Dr. V. A. 3 15565 Legator is a toxicologist with special emphasis on reproductive toxicology and environmental toxicology; general causation expert on the extreme toxicity and carcinogenicity of tcdd ; specific causation on the causal relationship between exposure of the representative class plaintiffs and miscarriages experienced by their wives and the congenital malformations of their children; see curriculum vitae, all summaries, with references and documents attached; deposition testimony in possession of all parties. Direct examination estimated 1 day; Cross examination estimated 1 day. Dr. Peter Orris Division of Occupational Medicine, Cook County Hospital, Chicago, IL.: Dr. Peter Orris is practicing physician, specializing in internal medicine; general causation regarding tcdd intoxication of Vietnam veterans and diagnosis of tcdd syndromes; specific causation of illnesses of representative class plaintiffs as being the result of their Agent Orange exposure; see curriculum vitae, all summaries, with references and documents attached; deposition testimony of Dr. Orris is in the process of being completed and will be in the possession of all parties. Direct examination estimated 1 day; Cross examination estimated 1 day. Dr. Ronald Codario resulting illnesses 1427 South Broad Street, Philadelphia, PA.: Dr. Codario will testify to acute and chronic toxicity of herbicides and tcdd in animals and humans as a medical doctor; general causation of adverse health effects of these herbicides and the extremely toxic tcdd; specific causation expert on the causal relationship between the Agent Orange herbicides and tcdd exposure of representative class plaintiffs and their and disease processes; see curriculum vitae, all summaries, with V. A. 4 1556S 3 Dr. John Garofalo references and documents attached; deposition testimony in possession of all parties. Direct examination estimated 1 day; Cross examination estimated 1 day. 847 Old Lancaster Road, Bryn Mawr, PA.: Dr. Garofalo is a medical doctor, who specializes on the immune system; general causation expert on the effects of Agent Orange herbicides and tcdd on the immune system; specific causation on the causal relationship of the adverse health effects in the representative class plaintiffs; see curriculum vitae, all summaries, with references and documents attached; deposition testimony will be in the possession of all parties as soon as it has been completed. Direct examination estimated 1 day; Cross examination estimated 1 day. Dr. Ernest Baran 833 Andorra Road, Lafayette Hills, PA.: Dr. Baran is a practicing psychiatrist specializlizing in electrodiagnostic testing of the peripheral and central nervous system, including somatosensory evoked potentials; general and specific causation expert on toxicity on Agent Orange herbicides and tcdd in the nervous system; see curriculum vitae, all summaries, with references and documents attached; deposition testimony will be in the possession of all parties as soon as it is completed. Direct examination estimated 3/4 day; Cross examination estimated 3/4 day. Dr. Herbert Kaye a battery of Department of Psychology, State University of New York at Stonybrook, Stonybrook, N.Y.: Dr. Kaye is a psychologist who has performed neurometric tests on the representative class plaintiffs, which testing system he has developed; general and specific causation expert on the toxic effect of Agent Orange herbicides and tcdd and chemicals and their ability to V. a . 5 1 5567 Dr. Raymond Singer Dr. Lennart Hardell Dr. Marvin Schneiderman alter the neuroraetric responses ; see curriculum vitae, all summaries, with references and documents attached; deposition testimony will be in the possession of all parties as soon as it is completed. Direct examination estimated 3/4 day; Cross examination estimated 3/4 day. 402 East 90th Street, Suite 6B, New York, N.Y.: Dr. Raymond Singer is a neurotoxicologist and neuropsychologist who will appear as a general and specific causation expert on the extremely harmful and toxic effects of Agent Orange herbicides and tcdd on the human nervous system and the representative class plaintiffs; see curriculum vitae, all summaries, with references and documents attached; deposition testimony is in the possession of all parties. Direct examination estimated 3/4 day; Cross examination estimated 3/4 day. Department of Oncology, University Hospital, Uraea, Sweden.: Dr. Hardell has a Ph.D. and M.D. and is an oncologist; he has performed epidemiology studies which evaluate the increased risk to humans for the development of various types of cancer from exposure to phenoxy herbicides such as the Agent Orange herbicides contaminted with tcdd; general and specific causation expert; see curriculum vitae; all summaries, with references and documents attached; deposition of Dr. Hardell will be in the possession of all parties as soon as it has been completed. Direct examination estimated 1 day; Cross-examination estimated 1 day. 6503 East Halbert Road, Bethesda, Maryland.: Dr. Schneiderman is a Clement Associates Senior Science 15568Advisor with principal V. A. 6 responsibilities in biostatistics, epidemiology, risk assessment, and health surveillance; special qualifications in cancer research; general and specific causation expert; see curriculum vitae; all summaries, with references and documents attached; deposition testimony in possession of all parties. Direct examination estimated 1 day; Cross-examination estimated 1 day. Dr. Theodore Sterling Department of Computer Science, Simon Fraser University, Burnaby, British Columbia, Canada: Dr. Sterling is a professor of computer science at Simon Fraser University, Vancouver, British Columbia, Canada with specialties in mathematics, statistics, and epidemiology; general causation expert on the analyses concerning the effects of 2,3,7,8 tcdd, phenoxy herbicides, including Agent Orange and their impurities on humans; see curriculum vitae; all summaries, with references and documents attached; deposition testimony in possession of all parties. Direct examination estimated 3/4 day; Cross-examination estimated 3/4 day. Dr. Janet Springer Environmental Protection Agency, Washington, D.C.: Dr. Springer is a biostatistician for the Environmental Protection Agency who has testified as to her work on dioxin risk model and the use of animal data to extrapolate for the risk of developing cancer in humans at EPA; see curriculum vitae and deposition testimony which is possession of all parties. Direct examination estimated 3/4 day; Cross examination estimated 1/2 day. Dr. Debdas Mukerjee Environmental Criteria & Assessment Office, Environmental Protection Agency, Cincinnati, Ohio: Dr. 15589 V. A. 7 Dr. Vernon Houk Dr. Steven Bayard Mukerjee is the document manager for the EPA, and responsible for the publication of the draft dioxin documents for the Offices of Air Quality, Solid Waste, and Water in the EPA, (at this time, only the Office of Water Regulations and Standards, Ambient Water Quality Criteria for 2,3,7,8 Tetrachlorodibenzo-p-dioxin, has been published in final form); see deposition testimony, and exhibits attached thereto, and documents in the process of being produced by the government in the possession of all parties. Direct examination estimated 1/2 day; cross examination estimated 1/2 day. Center For Disease Control, National Institute For Occupational Safety and Health, Atlanta, Georgia: Dr. Houk is the Director of Center of Environmental Health for the Center of Disease Control (CDC) Atlanta, Georgia, and has conducted and is conducting investigations with cooperation- of the States for the identification of dioxin contaminated sites in the United States; initiating clean-up procedures; prevention of future exposure of residents to dioxin in the environment in order to protect the public health from an extremely potent toxic substance "2,3,7,8 tcdd"; he has developed models to make risk assessments for residents of the United States exposure to dioxin; general causation expert on toxicity of tcdd; persistence in soil and in the environment; adverse health effects; see deposition testimony and exhibits attached thereto in possession of all parties. Direct examination estimated 3/4 day; cross examination estimated 1/2 day. Cancer Assessment Group, Environmental Protection Agency, Washington, D.C.: Dr. Bayard is 15570 V. A. 8 Orange in Vietnam; his physical pain and mental anguish; see deposition testimony and exhibits attached thereto in the possession of all parties. Direct examination estimated 1-1 1/2 days; Cross examination estimated 1 day. Michael Ryan Plaintiff. 73 University Heights Drive, Stonybrook, New York: Michael Ryan will testify to his exposure to Agent Orange in Vietnam; his physical condition, illnesses, injuries, and damages resulting from said exposure; the extreme emotional trauma resulting from the birth of his daughter Kerry with over 22 birth defects; his daughter's illness, malformations, injuries and damages; the tragedy reeked upon his family; see deposition testimony and all exhibits attached thereto in the possession of all parties. Direct examination estimated 1-1/2 days; Cross examination estimated 1 day. Maureen Ryan Mother of Plaintiff Kerry Ryan, and spouse of Plaintiff Michael Ryan. 73 University Heights Drive, Stonybrook, New York. Maureen Ryan, wife of Michael Ryan, and mother of Kerry Ryan, will testify as to the devastation upon her family, their illnesses, conditions, and injuries and damages as a result of her husband's exposure to Agent Orange in Vietnam; see deposition testimony in the possession of all parties. Direct examination estimated 1 day; Cross examination estimated 1/2 day. Kerry Ryan Plaintiff. 73 University Heights Drive, Stonybrook, New York. Final decisions from both defendants and plaintiffs as to whether any deposition will be attempted, and as to whether Kerry can testify have not been made. Plaintiffs reserve all rights, however, to introduce Kerry to the Court and jury and to present demonstrative evidence such as "day in the life of" films and V. A. 13 15571 bios tatician and biochemist with the cancer assessment group of the EPA and responsible for the testing of tcdd and the chemicals which contain it, which was the most toxic chemical of all 54 chemicals tested by EPA; general causation expert; see deposition and exhibits attached thereto in possession of all parties. Direct examination estimated 3 hours; Cross examination estimated 3 hours. Dr. Umberto Saffiotti National Cancer Institute, Washington, D.C.: Editor, New York Academy of Science Journal; Dr. Saffiotti is general causation expert, and will testify to the carcinogenicity, mutagenicity, fetotoxicity, acneigenicity, and teratogenicity of 2,3,7,8 tcdd in animals and humans; see deposition testimony and exhibits attached thereto in possession of all parties. Direct examination estimated 1 1/2 hours; Cross examination estimated 1 hour (Caveat: should plaintiffs elect to use deposition testimony the time taken will be less than 1 hour total). Dr. K.DianeCourtney RichardChristian Environmental Protection Agency, Washington D.C. and working at Triangle Park, Maryland Laboratories: Dr. Courtney is general causation expert with special emphasis on the toxic effects of dioxin on animals while working for EPA; see deposition testimony and exhibits attached thereto in possession of all parties. Direct examination estimated 3/4 day; Cross examination estimated 1/2 day. United States Army, Agent Orange Task Force, Pentagon, Washington, D.C.: Richard Christian is in the U.S. Army and is responsible for charting the exposure of all Vietnam veterans to Agent Orange and the other phenoxy herbicides sprayed in 15572Vietnam while comparing the location V. A. 9 and movement of all military units with the spray missions and plotting them on grid coordinates; general causation expert; see deposition testimony and exhibits attached thereto which deposition has not been completed as yet and will be in the possession of all parties prior to trial. Direct examination estimated 1 day; Cross examination estimated 1/2 day. Dr. Philip Landrigan Safety and Health, Center for Disease Control, National Institute for Occupational Safety and Health,Cincinnati, Ohio: Dr. Landrigan is with the Center for Disease Control, National Institute for Occupational Cincinnati, Ohio and is currently performing a risk assessment for occupationally exposed workers to dioxin and chlorinated phenols; see deposition testimony and exhibits attached thereto in possession of all parties. Direct examination estimated 1/2 day; Cross examination estimated 2 hours. Dr. Donald Barnes Office of Pesticides & Toxic Substances, Environmental Protection Agency, Washington, D.C.: Dr. Barnes is a biochemist. He has done extensive review of the scientific literature on dioxins and participated in the Peer Review of the EPA draft documents; see deposition testimony and exhibits attached thereto in the possession of all parties. Direct examination estimated 1/2 day; Cross examination estimated 2 hours. George Ewalt Plaintiff. 4351 Lauriston, Philadelphia, PA.: George Ewalt will testify to his individual exposure, as well to his research and mapping of the spray missions in Vietnam for Agent Orange, White, and Blue, and the locations of the various army units in which he and the other plaintiffs were exposed to Agent 15573Orange herbicide; Ewalt will testify V. A. 10 to basal cell carcinoma and other injuries and damages he has sustained as a result of his exposure to Agent Orange; Ewalt will describe his experience in Vietnam and the description of the effects of the defoliants; see deposition testimony of Ewalt with all production of documents attached thereto as exhibits (including photographs) and prior testimony of Ewalt before Senator Spector in Philadelphia, Penn. Direct examination estimated 1-1 1/2 days; Cross examination estimated 1 day. Dan Jordan the U.S. diseases Army, and Plaintiff. 7212 Sir Gawain, Austin, TX.: Dan Jordan will testify to his individual exposure in Vietnam to herbicide "Agent Orange", his research on the chemical compound, his experience while stationed in in Vietnam, his injuries and damages resulting from his exposure to Agent Orange in Vietnam while serving his country; see deposition testimony of Plaintiff and all exhibits attached thereto and/or produced for the defendants in Austin, Texas. Direct examination estimated 1-1 1/2 days; Cross examination estimated 1 day. Donna Jordan Plaintiff. 7212 Sir Gawain, Austin, TX.: Donna Jordan, wife of Dan Jordan, and mother of Michael and Chad Jordan, will testify to her husband's physical problems since his exposure to Agent Orange in Vietnam, her miscarriage; and the birth of her deformed children Chad and Michael as a result of her husband's exposure to Agent Orange; she will describe the permanent and substantial mental pain and anguish, as well as the physical injuries and other damages her family has sustained as a result of Agent Orange; see deposition testimony and all exhibits attached thereto and/or produced for the defendants. Direct examination estimated 1/2 day; Cross examination estimated 1/2 day. V. A. 11 15574 Chad Jordan Plaintiff. 7212 Sir Gawain, Austin, TX.: Chad Jordan, age 13, will testify as to his own physical malformation, condition, and the physical problems resulting therefrom; see deposition testimony in possession of all parties. Direct examination estimated 1 hour; Cross examination estimated 1/2 hour. Michael Jordan Plaintiff. 7212 Sir Gawain, Austin, TX.: Michael Jordan, age 11, will testify as to his own physical malformation, condition and the physical problems resulting therefrom; see deposition testimony in possession of all parties. Direct examination estimated 1 hour; Cross examination estimated 1/2 hour. Danny L. Ford Plaintiff. 3507 St. Anthony Road, Temperance, Michigan: Danny Ford served in infantry in Vietnam and will discuss his experience in Vietnam and in army; Ford will describe the conditions in Vietnam, his exposure to areas that had been defoliated; his problems, physical and mental as a result of his exposure to toxic herbicides and specifically Agent Orange; his physical diseases, injuries and damages resulting from this exposure; see deposition testimony in possession of all parties, and all exhibits attached thereto, including photographs taken while plaintiff was in Vietnam. Direct examination estimated 1-1 1/2 days; Cross examination estimated 1 day. David G. Lambiotte Plaintiff. 44 Westover Road, Newport News, Virginia: David Lambiotte has sustained basal cell carcinoma and lymphitic lymphoma as a result of his exposure to Agent Orange in Vietnam; Lambiotte will testify as to his physical and emotional problems, his injuries and damages as a result of his exposure to Agent V. A. 12 15575- Caveat: Demonstrative such other proper evidentiary techniques as become appropriate with respect to Kerry as a witness in her own behalf. Direct examination, if any would be extremely brief; estimated cross examination - none. evidence such as "day in the life" film would take 1-2 hours to present (estimated). D r . Thomas Aboud c/o Toledo Clinic, Toledo, Ohio: Mrs. Ford's cardiologist treated Danny Ford for hypertension; would testify to medical conditions, health and damage questions. Approximate length of direct testimony is 2 hours. Cross examination, 1/2 hour. Edward E. Adams Termination Contracting Officer, Defense Supply Agency, Defense Contract Administration Services Office (DCASO), 1136 Washington, St. Louis, MO.: testimony on issues of one or more of the defendants' failure to warn, procedures re government contract services and personal dealings with one or more defendants in these regards; Has not yet been deposed. Direct testimony and cross examination cannot be estimated at this time due to lack of deposition. Irene Antonik 812 Sussex, Austin, Texas; Texas disability officer and friend of Jordans' will offer testimony on health and damages issues from personal knowledge; has not yet been deposed. Direct examination estimated 2 h r s ; Cross examination estimated 1/2 hour. Eugene Bak* Defense Supply Agency Termination Contracting Officer, 200 Mill Street, Bellville, New Jersey: testimony on issues of one or more of the defendants' failure to warn of toxicity of the Agent Orange herbicides; witness has been deposed; Direct examination estimated 1-1 1/2 hours; Cross examination estimated 1/2 hour. V. A. 14 1557$ Donald Barnes Government causation expert from Environmental Protection Agency will testify on issues of general causation; has recently been deposed, but as of this writing, deposition transcript has not been abstracted due to press of time in preparing other portions of this pre-trial order. A more specific summary of the witness' testimony will be contained in first amended pre-trial order to be filed. E.E. Baumgartner Inspector, Defense Contract Supply Agency Office, Little Rock AFB, Arkansas: Testimony regarding government relationship with supplies of Hercules, Incorporated as it pertains to failure to warn issues; witness has not yet been deposed. Direct and Cross examination lengths impossible to estimate at this time. R.E. Baynard Monsanto government products supervisor, 231 Jeffrey Lane, Newtown Square, PA. 19073: Testimony re health problems among workers and failure to warn issues; toxicity knowledge re end product; has not yet been deposed; therefore length of Direct and Cross examinations presently impossible to estimate. Jeannie Beavers Flower Hospital, Personnel Department, Sylawia, Ohio: Personal observations regarding effects on plaintiff Danny Ford of his illness, both as to physical and emotional pain and suffering and hospital and business strains caused by illness; Direct examination estimated 1 hour; Cross examination estimated 10 minutes. Billie Marie Bell Personal observations 4404 Bonnie Drive, Ft. Worth, Texas: regarding health and development throughout life, both pre and post Vietnam service of Danny Jordan. This witness is his mother; Direct examination estimated 1 1/2 hours; cross examination 15577estimated 15 V. A. 15 minutes. Cloyci G. Bell 4404 Bonnie Drive, Ft. Worth, Texas: Personal observations regarding the health and damages issues as they pertain to Plaintiff Danny Jordan. This witness is his step-father. Direct examination estimated to be maximum of 1 hour; cross examination expected to be very brief. Bell Telephone of PA 1 Park Way, Philadelphia, Pennsylvania: Records of employment and working history, to be presented to the extent necessary by an individual to be chosen from the company; to the extent such live testimony is required, plaintiffs will include such witness as soon as identified by the company in up-date or amendment to pre-trial order. Examination expected to be very brief or subject of a request for stipulation from defendants; if no stipulation achieved, maximum estimated direct examination 1 hour; Cross examination estimated maximum 1/2 hour. Wilton B. Bills Contract Officer, Defense General Supply Center, Richmond, VA: Information regarding the contract negotiating process pertaining to all defendants, but esp., Dow and Hercules; has not yet been deposed; therefore presently impossible to estimate length of direct or cross examinations. Peter S. Bing, M.D.* 9700 Pico Boulevard, Los Angeles, CA.: Former White House Staff Member. Although Dr. Bing has been deposed, plaintiffs may call him as a Live witness at trial for the purpose of explaining the preparation of the President's Science Advisory Committee Report regarding the Use of Pesticides in the United States; relevant to lack of government knowledge; Direct examination estimated 1 hour; cross examination estimated 1/2 hour. V. A. 16 15578 Etcyl H. Blair Direct examination 4 Crescent Court, Midland, Ml.: Vice President, Dow Chemical, and Director of Health and Environmental Sciences; has been deposed; He has been employed by the Company since 1951. Dr. Blair will testify as to his involvement with the use and production of herbicides by the Dow Chemical Company. In addition, he will testify as to his involvement with various committees of Dow such as the Risk Assessment Committee. We are currently awaiting the transcript of the second day of the Blair deposition so that we can include any additional supplemental material as may be indicated and required. estimated 2 hours; cross examination estimated 1/2 hour. John Blish A.A. Block Joseph L. Bolton Defense Fuel Supply Agency, Washington, D.C.: Information regarding negotiation, fulfillment, and termination of government contracts; witness' particular responsibilities related to Diamond Shamrock Corporation; has not yet been deposed; therefore presently impossible to estimate length of direct and cross examinations. Chemical Inspector, Defense Contracting Ageny Supply Region (DCASR), Quality Assurance Representative, Kansas City, Missouri: Information relative to the inspection of herbicides supplied relative to inspection practices, and procedures actually employed, with particular knowledge of T H Agriculture & Nutrition Company; has not yet been deposed; therefore presently impossible to estimate length of direct or cross examinations. Chemical Inspector, Defense Contracting Administrative Services Region (DCASR), 500 South Ervay St., Dallas, TX. 75201: Information re; inspection and acceptance of deliveries, with particular V. A. 17 15579 Jack Borrer Al Bothwell James E. Bowers Daniel Braxton Dave Bunin Emil Christofano knowledge of Hercules, Incorporated, and general knowledge of procedures employed from time to time during herbicide delivery periods; has not yet been deposed; therefore presently impossible to estimate length of direct or cross examinations. 12920 Wellswood Trail, Chesterland, Ohio: former Diamond Shamrock employee having testimony relevant to severe contamination of company's manufacturing plant and end product with knowledge of health hazards. If this witness cannot be produced, plaintiffs will append a page and line summary of his deposition to their next submission. Expected length of testimony less than 1/2 day. 610 Hudson Terrace, Newport News, Virginia; friend of David Lambiotte's - health and damage witness; total testimony less than 1 1/2 hours. 313 N. Midwest Boulevard, Midwest City, Oklahoma: Defense Supply Agency, Administrative Contract Officer, Defense Contracting Services Office, Kansas City, MO.(during relevant periods): particular knowledge regarding contracts of government with T H Agriculture & Nutrition; has not yet been deposed; therefore presently impossible to estimate length of direct of cross examinations. Address to come; George Ewalt's foreman. Philadelphia, Pennsylvania; professional economist who will evaluate damages of individual plaintiffs. -Expected length of testimony 1/2 day. Hercules Towers, Wilmington, Delaware.; Deposed February 9 & 10th, 1984; Expert and Fact Witness; Industrial Hygienist at Hercules 15580 V. A. 18 J. G. Copeland, Jr. George and Marge Crawfis since approximately 1957; his job responsibility from 1964 through 1975 was to be aware of health hazards possibly presented to employees or to persons handling the product or to persons at risk as product would be used by the customer. The health hazard (nature, magnitude or extent of the injury) can be dependent upon the amount of exposure (and strength of the poison) at a given time; the frequency of exposure, and the route or method of exposure (tender skin, tough skin, oral, breathing, etc.). He will testify to the matters in and the exhibits to his deposition. He has no knowledge of anybody at Hercules ever informing anybody in the government of the existence of dioxin in the 2,4,5-T product. He denies ever receiving knowledge tha the 2,4,5-T produced by Hercules in 1965 contained any measurable dioxin. Estimated length direct testimony 1 1/2 hours; Examination by defendant's unknown, but assume 30 minutes. Assistant General Manager, '64 Gen. Mgr. Synthetics,'65-72 of Hercules; Plaintiffs note that Mr. Copeland's deposition was scheduled for 3/30/84, but continued with the agreement of all defendants due to the witness's inability to appear (a tree fell on his house in a storm). After his deposition has been taken and the transcript received and reviewed, plaintifffs will update this portion of the pre-trial order accordingly. Plaintiffs are not now certain if Mr. Copeland will be a live witness or a deposition witness. The Exhibit List will also be amended accordingly, depending upon developments at the deposition. 49 Heck R d ., Kennessaw, Georgia; Dan Ford's brother and sister-in-law; overall physical, emotional and financial conditions suffered by Fords. Total testimony time 1-2 hours. V. A. 19 155E^ Owen and Betty Crawfis Bill Curtis Charles L. Dunn 61-83 Whiteford Center Rd., Toledo, Ohio; Mrs. Ford's parents to testify to Dan's physical and emotional conditions, his medical treatment, personality changes, increasing stress, job difficulties, wage losses, and effects on the Ford family. Total testimony time 1-2 hours. c/o CBS News, 524 West 57th Street, New York, New York; Eyewitness observations as to the condition of the country of Vietnam, extent of residual defoliation, photographic exhibits. Expected length of total testimony 1/2 day. Wilmington, Delaware; First employed at Hercules, 1942 as a chemist & was Manager of regulatory affairs from 1960 through 1965 and then became manager of Ag Chemicals development until 1969. From August, 1966 he served as Hercules' representative on the INdustry Task Force on Phenoxy Herbicides, National Agriculture Chemicals Association (NACA) and became Vice Chairman in August, 1966 and Chairman from October 17, 1967. The task force duties were to represent industry before the Department of Agriculture and the Department of Health, Education & Welfare. To augment the safety of current registration practices, the Secretary of Agriculture selected a panel from the National Academy of Sciences to re-evaluate toxicological data on pesticides and NAS recommended a system of negligible residue tolerances be established. Notwithstanding the legal duty imposed by regulations and law (said duty well known to Dunn, Hercules, NACA & the task force & each of its members (all of the defendants herein being members) & by the past common and accepted practices of the industry generally thedefendants, specifically, the fact of Agent Orange contamination with dioxin in V. A. 20 J.M. Eagan the 2,4,5-T was not only not made known to the government (Department of Agriculture, HEW, U.S. Military); the fact of contamination by dioxin was intentionally, maliciously, & for the purpose of greed, secreted from the government through the individual and concerted acts and conduct of members of the Task Force. Because Mr. Dunn is presently under Hercules contract to perform consulting services, he was produced for his discovery deposition on 4/28/83 at Hercules' offices in Wilmington, and was again produced for further deposition on March 8, 1984 (the latter transcript has not yet been received). In view of the Court's discussion on April 2, 1984, it is assumed the court will order Mr. Dunn to be presented for live testimony. If not, plaintiffs will promptly indicate the testimony to be read from the transcripts. Mr. Dunn will testify to all documents marked as exhibits at his depositions on file herein, and dated 5/2/83. He will testify to the March 24, 1965 meeting among the manufacturers, the conspiracy growing therefrom, his knowledge of the hazard, of Hercules pre-1966 production of 2,4,5-T & the hazards of products of others (with which Hercules' was . mixed.) Direct examination estimate at 3 hours; Examination by defendants presumed at 1 hour. 45 Cypress Marsh Dr., Hilton, Head, S.C.; deposition taken 3/30/84; Plaintiffs provide the following, however, on a non-binding basis, subject to amendment and augmentation: Mr. Eagan was formerly Hercules' Assistant Director of Operations, Synthethics,(1961-65) and Director of Operations (1965-68); will testify concerning the manufacture of and manufacturing processes for 2,4,5-T, Agent Orange, and phenoxy-herbicides; Hercules' Jacksonville Arkansas plant; Knowledge concerning dioxin V. A. 21 15583 toxiciCy, and health hazards of dioxin and 2,4.5-T; detection and reduction of dioxin; sales to government, defendant's failure to advise or warn the government; registration of the herbicide; sales to Dow; purchase and use of foreign 2.4.5- T; issues re proposals concerning government plant at Muscle Shoals, Alabama, production at Edgewood Arsenal; the government's analyses of Agent Orange as to the % of 2,4-D and 2.4.5- T; specifications and contracts for herbicide orange; Hercules' business records (attached to deposition and to be added to Exhibit list where necessary) are documents which may be referred to and discussed ; plaintiffs reserve the right to notice his appearance as a live witness until further supplementation or waiver or order of court. George W. and Eunice Ewalt, Sr. 731 Penn Pines Blvd., Clifton Heights, Pennsylvania; George Ewalt's parents will testify concerning the health and damages issues pertaining to this plaintiff. John J. Ford Hercules chemist; 15 Winterbury Circle, Wilmington, Delaware; expert and fact witness; Deposed at Hercules' office February 9, 1984; Designed and used the dioxin detection method and measuring system; will testify to matters covered in deposition and exhibits therein identified. Will demonstrate that Hercules' pre, 1966 product contained well in excess of 1 part per million and that testing equipment not valuable below 1 ppm. The test results of Hercules generally showed a greater amount of dioxin than Dows testing allegedly revealed. Though Hercules recognized its testing methods were inadequate and perhaps unreliable; they did nothing to attempt to improve them until after government V. A. 22 15584 Kerry Ford Jeanette Ford Ray Ford Rose Ford John P. Frawley decertified 2,4,5-T; Examination by plaintiffs approximately 1 1/2 hour; examination by defendants unknown but assumed to be 1/2 hour. 6507 Secore Drive, Lambertville, Michigan; health and damage witness; total testimony 1 hour. 6507 Secore Drive, Lambertville, Michigan; health and damage witness; total testimony 1 hour. 13478 South Country Line Highway, Ottowa Lake, Michigan; health and damage witness; total testimony 1 hour. 13478 South Country Line Highway, Ottowa Lake, Michigan; health and damage witness; total testimony 1 hour. Wilmington, Delaware; Ph. D. Biological Chemistry; Deposed March 8, 1983, and February 7 & 8, 1984; Testified in deposition and at trial of Vertac case as described more fully under witness A.E. Sidwell; will testify to matters included in the above proceeding & the attached exhibits; "its the most toxic man made chemical in my opinion, that has been detected so far, and because if it's extreme toxicity, we have to look for it in parts per trillion and parts per billion range..." It is more toxic than strychnine, arsenic or thalidomide...."at 559 parts per billion I would consider that to be a potentiontial health hazard... I would not consider it safe to walk on barefoot." Regarding the level that might be considered safe, he testified that "I think I'd consider 10,000 parts per trillion as getting significant and this would be 10 parts per billion" (and further, would be .01 parts per million.) He has urged that a standard should be set which would allow 1 ppm dioxin, but this has been rejected as too 15585 V. A 23 Francis Kennedy Carl & Carla King Harry E. Soehner Mr. Kenaga was a prime contact within Dow for Uniroyal personnel, as well as having substantial knowledge concerning the toxicity and environmental persistence of dioxin. Testimony length 2 hours. 2711 Bernadett Lane, Houston, TX; Mr. Kennedy was the Diamond Shamrock Plant Manager of the Newark plant from 8-1-63 to 9-9-68, which plant experienced numerous and severe health problems among its workers; he was deposed on 1-21-83; generally, his testimony will focus on knowledge of Newark's health problems from 1954 to 1968 which he characterizes as a serious problem; was attendee at the Dow March 24, 1965 meeting; knowledge of dioxin, its toxicity and danger to human health; he supervised Newark's dioxin detection and removal program and will establish the dioxin levels for the months and years he was manager; on failure to warn and product defect isssues, and the claim of confidential knowledge of manufacturing processes. Although no longer employed, plaintiffs claim he should be produced as a live witness. 33-42 Romaker, Toledo, Ohio; closest friends of the Danny Fords; she was with Chris when learned of cancerous condition of Danny's leg and will testify on health, pain, suffering, and other damage issues. Total length of testimony 1 1/2 hours. Uniroyal employee since 1933 (retired in 1974), was in charge of safety supervision. First heard of dioxin in 1961 and learned that it caused chloracne, and learned in .- -- --- f-H-n-v-i-n -- ~a nf-n-f-An-M-*--a-l carcinogen; will describe the fact that he attended many meetings at Uniroyal relative to the health risks of the chemical. He is being listed in this live witness list, however, it is anticipated that on amendment of this pretrial order, he V. A. 26 will be transferred to the deposition witness list. It is impossible to presently comply with the requirement to give a page and line referenced summary for that purpose, since his deposition was taken so recently that the transcript has not yet been received. Edward Hager A technical associate with Uniroyal, Ltd. formerly in research and development at the Elmira plant, first heard of the dioxin problem in 1965 subsequent to the memo re ceived from Dow. Prior to that memo he was aware that it caused Chloracne. Learned that dioxin was in fact a carcinogenic in the Seventies. States that Uniroyal did no testing to determine dioxin content at end product line. Testified that technology was available during the mid-1960's to better analyze for dioxin content. States that Uniroyal didn't feel it was necessary to perform tests during the manufacturing process. He is listed on the live witness list, however, it is anticipated that upon amendment of , the pretrial order that he will be listed as a witness by deposition. It is impossible to comply with the requirement to give a line and page summary of this witnesses testimony as his deposition was taken so recently that a copy of the transcript is presently unavailable. William Shipley Witness began working for Uniroyal in 1950 as an assistant control chemist. Presently he is in commercial development. Claims he did not know of the term dioxin until after Love Canal in 1981. Presently the Environmental Liason between Uniroyal, Ltd., Elmira Plant and the Canadian Government. He is listed on the live witness list, however, it is anticipated that upon amendment of the pretrial order that he will be listed as a witness by deposition. It is impossible to comply with the requirement to give a line and page summary of this witnesses V. A. 27 15587 * testimony as his deposition was taken so recently that a copy of the transcript is presently unavailable. Taylor H. Evans Evans started with Uniroyal, Ltd. in 1943 and holds a Ph.D. in Chemistry. He attended the Dow meeting at Midland on 8/3/65 to discuss the Dioxin problem. He was aware of the Hoechst Plant industrial accident in Germany where two workers died and others had liver damage. He did not reveal his knowledge of the "Dioxin Problem" to the Safety Supervisor at the Elmira Plant learned at the Dow Midland meeting on 8/3/65. In a memo prepared concerning the Dow meeting he noted that Dow said that no product containing dioxin should be sold and that no discussion regarding the problem should be had outside of the division. He is listed on the live witness list, however, it is anticpated that upon amendment of the pretrial order that he will be listed as a witness by deposition. It is impossible to comply with the requirement of a line and page summary of his test imony as his deposition was taken so recently that a copy of his transcript is presently unavailable. Lucien G. Maury 29 Brandywine Road, Wilmington, Delaware; Hercules, V.P. of Technology; research chemist; Manager, synthetics research, 1961-64; Manager Corporate research 1964-67; Assistant Director of Research 1967-71; Ph. D. Chemistry. Not aware of product 2,4,5-T and did not know anything about potential of contaminant; because of his positions, he would have been expected to have been informed of a possible toxic material but he was not - no information regarding dioxin ever came to him; Examination of plaintiff approx. 45 minutes; Examination by defendants unknown, but assume 15 minutes. Robert Bates Scott 609 North DuPont Road,' Wilmington, Delaware, 19807; currently employed V. A. 28 1552B Leonard Davenport Mr. Larry List Mr. Charlie Hartz, deed. JOHN WILDER TUKEY CHARLES H. TOWNES WILLIAM MC ELROY 3104 Warbler Drive, Montgomery, Alabama; to be asked to testify to the circumstances of the loading, unloading spraying and defoliation as he observed it take place when he was in Vietnam; expected length of testimony 1 1/2 hours. P.0. 18 Birchrunville, Pennsylvania 19421; will be asked to testify to his observations of the spraying and its affect upon men he observed having reactions to it during his tour of duty in Vietnam, expected length of testimony 1/2 hour. Excerpts from his video taped deposition will be offered with respect to his observations of the spraying and defoliation process during his tour of duty. PSAC Member from 1960 to 1963. Also a member of the ad hoc panel on herbicides. First knowledge of dioxin is in 1969. Whether this witness is produced live or through deposition excerpts awaits ruling of Court. 1988 SAN ANTONIO AVE, BERKELEY, CALIF. Member, Science Advisory Board of Air Force(l958-1961), Vice President and Director of Research of the Institute for Defense Analysis (1959-1961). No discussion of health effects of herbicides prior to 1970. Whether this witness is produced live or through deposition excerpts awaits ruling of Court. 9651 BLACK GOLD RD., CALIF. Member of PSAC Panel on the use of Pesticides. Does not recall any chemical company coming forward to report health effects of 2,4,5-T, and did not consult with PHS on the matter. ' Whether this witness is produced live or through deposition 15589excerpts awaits ruling of Court. V. A. 32 BETTY SMAYDA TERRY AND JEANNETTE FORD RAY AND ROSE FORD ju d y m ckin ley ROBERT SNODGRASS traveled to by foot and by vehicle, and the conditions of their unit while in these various locations. Less than 1/2 day total testimony. 1809 Rapids Road, Hiram, Ohio. Betty Smayda, a long-time friend and busines associate of Mrs. Danny Ford, will testify to Danny Ford's physical and emotional conditions, his behavior changes and increasing stress, the resultant time and wages lost in Danny Ford's work, and the overall emotional and financial strainson the Ford family. Less than 1/2 day total testimony. 6507 Secor Road, Lambertville, Michigan. Terry and Jeannette Ford will testify to the Ford family's physical, emotional and financial strain which they observed as Danny Ford's brother and sister-in-law. Less than 1/2 day total testimony. 13478 South County Line Highway, Ottawa Lake, Michigan. Danny Ford's parents will testify to his behavioral changes, physial conditions, increasing stres and the subsequent financial and emotional strain on the Ford family. Less than 1/2 day total testimony. 1899 Rapids Road, Hiram, Ohio. As a long-time friend and business associate of Christina Ford, Judy McKinely will testify to Danny Ford's emotional and physical conditions, behavioral changes, stress and the resulting financial and emotional strains suffered by the Ford family. Less than 1/2 day total testimony. Huntington, W. Virginia; In the same gun section as Danny Ford, Robert Snodgrass will testify to the various locations of their unit, including the recently defoliated areas they travelled by both vehicle and foot, as well as the conditions of their unit in the various areas. 15590Less than 1/2 day total testimony. V. A. 34 DAN TWISS JANE WARD SHERRY MOSHER HARRY HOLLAND MICHAEL LAMBIOTTE RICHARD SCOTT Woodland Street, Sylvania,Ohio. Dan Twiss, the Union Committeeman at Jeep Corporation and long-time friend of Danny Ford, will testify to the lost time and reduced wages of Danny Ford's work as a result of his physical condition. Less than 1/2 day total testimony. 3527 M.151, Temperance, Michigan. As the Fords' neighbor, Jane Ward will testify to the time and wages lost from both Danny Ford and Christine Fords' jobs as a result of Danny Ford's medical condition. Less than 1/2 day total testimony. 184335 Westchester Road, Toledo, Ohio. As the Manager of Christina Ford's business, SherryMosher will testify to Danny Ford's physical condition, the amount of time that Christina Ford has missed from work as a result of Danny Ford's condition and subsequently, the amount of business and wages lost in her absence. Less than 1/2 day total testimony. 1626 Dryden Way, Crofton, MD; As a friend of David Lambiotte's before, during and after his stay in Vietnam, Harry Holland will testify to David's behavioral changes, increased stress, irritability and other emotional changes. Less than 1/2 day total testimony. 18 Milford Rd., Newport News, Virginia; As David Lambiotte's brother, Michael Lambiotte will testify to David Lambiotte's emotional and behavioral changes, increased stress and depression since his return from Vietnam. Less than 1/2 day total testimony. 11 White Oak Drive, Newport News, Virginia; As David Lambiotte's high school friend, after spending time with David Lambiotte in Vietnam and after being David Lambiotte's 15531roommate after Vietnam, Richard V. A. 35 HENRY SADLER DR. SALTER GEORGE AND MARGE CRAWFIS JOHN CRAWFIS Scott will testify to David Lambiotte's attitude, behavior and emotional changes, his increased stress and his depression. Less than 1/2 day total testimony. Melbourne Beach, Florida. As David Lambiotte's neighbor and friend before and after Vietnam, Henry Sadler will testify to David Lambiotte's behavior and attitude changes, his increased irritability, depression and stress. Less than 1/2 day total testimony. 97 York Street, York, Maine; David Lambiotte's treating physician will testify to David as scientist and toxicologist; chief toxicologist for the Environmental Defense Fund; Research scientist in Reproductive Toxicology for National Institute of Health; general causation expert on the extreme toxicity, neuro-toxicity, reproductive toxicity, and carcinogenicity of Agent Orange and TCDD; mechanisms for the male-mediated birth defects; specific causation on the birth defects of Kerry Ryan, and Michael and Chad Jordan, was related to and caused by their respective fathers' exposure to Agent Orange in Vietnam; see curriculum vitae, all summaries, with references and documents attached; deposition testimony in possession of all parties. Direct examination estimated 1 day; Cross examination estimated 1 day. 49 Heck Road, Kennessaw, GA; Mrs. Dan Ford's brother and sister-in-law. Will testify to the overall physical, emotional and financial conditions suffered by the Fords which they observed as close relatives. Total testimony less than 1/2 day. 1179 Beach ValleyRoad, Atlanta, Georgia. Mrs. Ford's brother, John Crawfis, will testify to Danny Ford's emotional and physical conditions, t h e o f his V. A. 36 OWEN AND BETTY CRAWFIS Ronald Moody William Duffield Theodore C. Sorensen Lawrence O'Brien physical condition upon his employment and subsequently, upon the Ford family's overall financial status. Total testimony less than 1/2 day. 61-83 Whiteford Center Road, Toledo, Ohio. Mrs. Ford's parents will testify to Dan's physical and emotional conditions, his medical treatment, his personality changes and increasing stress, the limitations created by his physical condition in his job, the subsequent wage loss as a result of these limitations, and the effects of these conditions on the Ford family. Total testimony less than 1/2 day. c/o 65 Rodman Oval, New Rochelle NY 10805; Witness was a Ranch Hander and will testify to the practice and procedures of Operation Ranch Hand and the resultant exposures to Ranch Handers and other troops. Total testimony less than 1/2 day. 1115 Greenhill Lane, Box 485, Phoenixville, Pennsylvania 19460; He will testify concerning exposure of the plaintiffs and identify certain photographs. 345 Park A v e ., New York, New York; Mr. Sorensen was a member of the White House staff during the Kennedy administration and may testify that President Kennedy made the initial decision to undertake defoliation in Viet Nam and neither he nor President Kennedy or anyone on his White House staff, as far as he knew, was aware that the herbicides were contaminated with dioxin and potentially posed adverse health hazards to human beings. Direct Examination estimated 1/2 day; Cross examination estimated 1/4 day. New York, New York; Mr. O'Brien was a member of the White House staff during the Kennedy administration and may testify that President Kennedy made the initial decision to V. A. 37 John Siegentholeau Bill Moyers Josh Valenti undertake defoliation in Viet Nam and neither he nor President Kennedy or anyone on his White House staff, as far as he knew, was aware that the herbicides were contaminated with dioxin and potentially posed adverse health hazards to human beings. Direct examination estimated 1/2 day; Cross examination estimated 1/4 day. Nashville, Tennessee; Hr. Siegentholeau was a former member of Attorney General Robert F. Kennedy's staff and may testify that Kennedy made the initial decision to undertake defoliation in Viet Nam and neither he nor Kennedy or anyone on his staff, as far as he knew, was aware that the herbicides were contaminated with dioxin and potentially posed adverse health hazards to human beings. Direct examination estimated 1/2 day; Cross examination estimated 1/4 day. c/o P.B.S., 475 L'enfant Plaza, Washington, D.C. 20024; Mr. Moyers was a member of the White House staff during the Johnson administration and may testify concerning decisions regarding the deployment of herebicides in Viet Nam and neither he nor President Johnson or anyone on his White House staff, as far as he knew, was aware that the herbicides were contaminated with dioxin and potentially posed adverse health hazards to human beings. Direct examination estimated 1/2 day; Cross examination estimated 1/4 day. Motion Pictures of America, Washington, D.C.; Mr. Valenti was a member of the White House staff during the Johnson administration and may testify that President Johnson made the initial decision to undertake defoliation in Viet Nam and neither he nor President Johnson or anyone on his White House staff, as far as he knew, was aware that the herbicides were contaminated V. A. 38 Marvin Watson Walter Nastow Joe Califano with dioxin and potentially posed adverse health hazards to human beings. Direct examination estimated 1/2 day; Cross examination estimated 1/4 day. Dallas Baptist Univ., Dallas, Texas; Mr. Watson was a member of the White House staff during the Johnson administration and may testify that President Johnson made the initial decision to undertake defoliation in Viet Nam and neither he nor President Johnson or anyone on his White House staff, as far as he knew, was aware that the herbicides were contaminated with dioxin and potentially posed adverse health hazards to human beings. Direct examination estimated 1/2 day; Cross examination estimated 1/4 day. Lyndon Johnson Library, Austin, Texas; Mr. Nastow was a member of the White House staff during the Johnson administration and may testify concerning the White House decision making process from time to time relative to the deployment of herbicides in South East Asia and neither he nor President Johnson or anyone on his White House staff, as far as he knew, was aware that the herbicides were contaminated with dioxin and potentially posed adverse health hazards to human beings. Direct examination estimated 1/2 day; Cross examination extimated 1/4 day. Washington, D.C.; Mr. Califano was a member of the White House staff during the Johnson and Carter administrations and may testify concerning decisions regarding the herbicide program and neither he nor President Johnson, President Carter or anyone on his White House staff, as far as he knew, was aware that the herbicides were contaminated with dioxin and potentially posed adverse health hazards to human beings. Direct examination estimated 1/2 day; Cross examination 155S*i V. A. 39 Mr. Bourland Mr. Pearson estimated 1/4 day. Address being furnished by the Government. Dr. will testify that he was with the U.S. Army Biological Laboratories and will testify that in preparing the specifications for Agent Orange, Mr. C.H. Russell from Monsanto provided the basic specifications for Agent Orange and that the government relied upon the defendants to have done the testing to insure that the product was safe for use. He will further testify that the contract and dealings imposed upon the defendant have minimal and general requirements leaving substantial discretion in the defendant as to how the Agent Orange would be designed, formulated and manufactured. His deposition was taken and the pretrial order will be supplemented with the deposition line and page summary soon after the copy is transcribed and delivered to us. Plaintiffs' examination approximately 1/2 day; Defendants' cross approximately 1 hour. Address being furnished by the Government. Dr. will testify that he was with the U.S. Army Biological Laboratories and will testify that in preparing the specifications for Agent Orange, Mr. C.H. Russell from Monsanto provided the basic specifications for Agent Orange and that the government relied upon the defendants to have done the testing to insure that the product was safe for use. He will further testify that the contract and dealings imposed upon the defendant have minimal and general requirements leaving substantial discretion in the defendant as to how the Agent Orange would be designed, formulated and manufactured. His deposition was taken and the pretrial order will be supplemented with the deposition line and page summary soon after the copy is transcribed and delivered to us. Direct V. A. 40 155SS Paul Ignatius Albert E. Hayward George Collins Dr. Daniel Teitlebaum examination estimated 1/2 day; Cross examination estimated 1/4 day. Washington, D.C.; Government procuring his address; He was Assistant Secretary of Defense for Installation and Logistics and was General Stanwix Hay's immediate superior. He may testify live and will probably corroborate Gen. Stanwix-Hay's testimony that Secretary of Defense or President were ultimate decision makers with reference to Agent Orange and that no information concerning dioxin or adverse health effects passed up to the Secretary of Defense. Direct examination estimated 1/2 day; Cross examination estimated 1/4 day. (address being provided by the Government) He was Chief of the Program Coordination Office at Ft. Detrick. He will testify that at the first "Defoliation Conference" with the Defendants in 1963 at the United States Army Biological Laboratories, it was understood by all that the defoliation program in Southeast Asia would not be conducted in the usual way whereby the Government gives specific and rigidly enforced specifications but that the companies would be given broad and wish latitude in specifying, formulating and manufacturing the defoliants to be used. Direct examination estimated 1/2 day; Cross examination estimated 1/4 d a y . Address being provided by the government; he was a contracting officer with respect to several of the Defendants' contracts with the government. He may confirm Hayward's testimony and will confirm that Defendants failed to warn of any hazards in their Agent Orange products. Direct examination estimated 1/2 day; Cross examination estimated 1/4 day. Denver Clinic, 701 East Colax 155S7 V. A. 41 Dr. Gary Bokken Dr. William B. Retollick Dr. James 0. Rasmusson Avenue, Denver, Colorado; Dr. Teitlebaum is clinical toxicologist and occupational, environmental, and preventive medicine specialist. He will testify about the labelings, warnings, precautions, and advice that should have been used or given by the Defendants with respect to the Agent Orange and about the use of protective clothing, safety gear, safety systems, medical surveilance and other systems, tools, and techniques which could have reduced the risks to those who served in Viet Nam. Direct examination estimated 1/2 day; Cross examination estimated 1/4 day. 340 East Canyon View Drive, Tuscon, Arizona 85704; Dr. Bokken is a human factors and safety engineer. He will testify that considering the predictable human component involved in the use of the herbicides in Viet Nam, and the foreseeable uses and misuses of the product, the Defendants should and could have taken a lot of steps to eliminate or reduce the risks, including issuance of warnings, implementation of safety programs, and special training of the troops. Direct examination estimated 1/2 day; Cross examination estimated 1/4 day. 1432 Johnny's Way, Westchester, Pennsylvania 19380; Dr. Retallick is a Chemical Processing Engineer and he will testify that it was the state of the art, and the Defendants could and should have utilized processes to reduce the dioxin content in the end product. Exhibit references include the flow data sheets from this defendant which were filed with the Court in response to plaintiffs' interrogatories. Direct examination estimated 1/2 day; Cross examination estimated 1/4 day. 1582 W. 5th Place, Golden, Colorado 80403; Dr. Rasmusson is a specialist 155SSin analytical chemistry, V. A. 42 Dr. R. Kenneth Godwin Dr. Clifton D. Crutchfield Dr. Stephen Wyall instrumentation, general chemistry and environmental chemistry. He will testify that it was the state of the art in the 1960's and the precedent manfacture and sale of Agent Orange would have dictated that the product be tested through gas chromotography and other means to determine the levels of dioxin therein were too high. As an analytical Chemist he will discuss the chemical structure of TCDD and the phenoxy herbicides and their various chemical properties. Direct examination estimated 1/2 day; Cross examination estimated 1/4 day. 1447 W. Maxermillion Place, Wuscon, Arizon 85704; Dr. Godwin is a public policy analyst at the University of Arizona where his fields of expertise are environmental policy and the relationships between the bureaucracy and decision making. He will testify concerning the relationships between the various governmental agencies including the USDA, NIH, DOD, and other agencies dealing with toxic substances or and the Secretary of Defense and/or the President had the ultimate authority to use or continue to use herbicides in S.E. Asia. Direct examination estimated 1/2 day; Cross examination estimated 1/4 day. 7321 N. La Oester A v e ., Tuscon, Arizona 85704; Dr. Crutchfield is an industrial hygienist and will testify about the hazard control that should have been suggested and implemented in the form of an overall program by the Defendants in concert with the Government. Direct examination estimated 1/2 day; Cross examination estimated 1/4 day. Economics and Finance Dept., Univ. of Houston, Houston, Texas; Dr. Wyalt is a specialist in economics and will evaluate each of the Plaintiffs' economic loss. He will also analyze the financial worth of the Defendants as such information V. A. 43 Dr. Douglas Muster (if allowed) Dr. Rupert Burtan (if Charles Dishner A.J. Philo Billie Newton may be relevant to punitive damages. Direct examination estimated 1/2 day; Cross examination estimated 1/4 day. University of Houston, Houston, Texas; Dr. Muster is a mechanical and safety engineer. He will testify about the transport or safety experiences and safety audits in the workplace to place of use by the purchaser or end-user; he will also testify about equipment changes and process modifications that will help reduce the hazards in the end product; and about what constitutes an adequate warning for the Government to have been able to make a proper risk-utility apportionment decisions. Direct examination estimated 1/2 day; Cross examination estimated 1/4 day. Dr. Burtan is a doctor of occupational and environmental medicine. He will analyze the feasibility of warning the end-user, the solider in the field, in this case and of adopting a monitoring program suitable to that adopted by the Ethyl Corporation with respect to the ethyl lead. Direct examination estimated 1/2 day; Cross examination estimated 1/4 day. 401-A Capitol Landing Road, Williamsburg, VA. Vietnam Veteran will testify to conditions and circumstances related to spraying of Herbicide Orange in Vietnam at times relevant to the Representative Plaintiffs. Direct examination approximately 1/2 day; cross-examination 1/4 day. 2475 Pinson Highway, Tarant, AL. Vietnam Veteran will testify to exposures of David Lambiotte to Agent Orange, and will authenticate certain photographs. Direct examination approximately 1/2 day; cross- examination 1/4 day. 1560035 Town and Country Road, Leeds, AL. V. A. 44 Deborah Nelson Thomas Raftery Thomas Portagallo A1 Bothweel Vietnam Veteran served with David Lambiotte will testify to exposure of said plaintiff to Herbicide Orange and will authenticate certain photographs. Direct examination approximately 1/2 day; cross-examination 1/4 day. 2804 Jefferson Drive, Alexandria, VA. After being friends with, and after living with David Lambiotte, Deborah Nelson will testify concerning her observations of said plaintiff's physical and emotional conditions, including her knowledge of his seizure disorder, severe night sweating, stress, increased irritability, cancer and other medical conditions. Direct examination approximately 1/2 day; cross-examination 1/4 day. 2221 56th Drive, Brooklyn, NY. Vietnam Veteran who served with Plaintiff Michael Ryan will testify to Michael's significant weight loss and illness while in Vietnam as well as to the physical terrain of defoliated areas where Michael Ryan served while on Advanced Party missions. Plaintiffs' examination less than 1/2 day; defendants' examination brief. 106 Evans Road, Brookline, MA. Vietnam Veteran who served with Plaintiff Michael Ryan. He will testify concerning Michael Ryan's physical condition while in Vietnam, including his drastic weight loss, and other medical conditions. He will also attest to the physical terrain of the defoliated areas travelled by Michael's Advanced Party. Direct examination approximately 1/2 day; cross-examination 1/4 day. 610 Hudson Terrace, Newport News, VA. As a friend of David Lambiotte in high school, while they both served in Vietnam, and presently, A1 Bothweel will testify to the changes in David's physical and emotional JL O-I \t :j r , "i -.1 V. A. 45 Walter Jones, Jr. FRED FALANA CAPT. FARMER BETTY SMAYDA TERRY AND JEANNETTE FORD conditions before Vietnam to the present, including his increased stress, irritability, cancer, seizure disorders, and additional medical conditions. Direct examination approximately 1/2 day, cross-examination 1/4 day. 915 West Wilson Avenue, Chicago, Illinois; Mr. Jones worked at Hercules' Jacksonville Arkansas herbicide plant, in 1967 and 1968, and will testify concerning his observations and knowledge regarding the Plant's operations, including, but not limited to Agent Orange, wastes and waste disposal and workers' health problems, including his own. Estimated time of direct testimony is 1-2 hours, cross examination is unknown, possibly 1/2 hour. Address to come; As a member of Danny Ford's unit, Fred Falana will testify to the various locations which their unit was assigned, including recently defoliated areas traveled to by vehicle and often by foot, as well as the conditions of their unit in these various locations in Vietnam. Address to come; Captain Farmer will testify to the assigned locations of Danny Ford's unit, including the defoliated areas traveled to by foot and by vehicle, and the conditions of their unit while in these various locations. 1809 Rapids Road, Hiram, Ohio. Betty Smayda, a long-time friend and busines associate of Mrs. Danny Ford, will testify to Danny Ford's physical and emotional conditions, his behavior changes and increasing stress, the resultant time and wages lost in Danny Ford's work, and the overall emotional and financial strains on the Ford family. 6507 Secor Road, Lambertville, Michigan. Terry and Jeannette Ford 15808 V. A. 46 RAY AND ROSE FORD JUDY McKINLEY ROBERT SNODGRASS DAN TWISS JANE WARD SHERRY MOSHER will testify, to the Ford family's physical, emotional and financial strain which they observed as Danny Ford's brother and sister-in-law. 13478 South County Line Highway, Ottawa Lake, Michigan. Danny Ford's parents will testify to his behavioral changes, physial conditions, increasing stres and the subsequent financial and emotional strain on the Ford family. 1899 Rapids Road, Hiram, Ohio. As a long-time friend and business associate of Christina Ford, Judy McKinely will testify to Danny Ford's emotional and physical conditions, behavioral changes, stress and the resulting financial and emotional strains suffered by the Ford family. Huntington, W. Virginia; In the same gun section as Danny Ford, Robert Snodgrass will testify to the various locations of their unit, including the recently defoliated areas they travelled by both vehicle and foot, as well as the conditions of their unit in the various areas. Woodland Street, Sylvania,Ohio. Dan Twiss, the Union Committeeman at Jeep Corporation and long-time friend of Danny Ford, will testify to the lost time and reduced wages of Danny Ford's work as a result of his physical condition. 3527 M.151 , Temperance, Michigan. As the Fords ' neighbor, Jane Ward will testify to the time and wages lost from both Danny Ford and Christine Fords' jobs as a result of Danny Ford's medical condition. 184335 Westchester Road, Toledo, Ohio. As the Manager of Christina Ford's business, SherryMosher will testify to Danny Ford's physical condition, the amount of time that Christina Ford has missed from work as a result of Danny Ford's V. A. 47 HARRY HOLLAND MICHAEL LAMBIOTTE RICHARD SCOTT HENRY SADLER DR. SALTER \ condition and subsequently, the amount of business and wages lost in her absence. 1626 Dryden Way, Crofton, MD; As a friend of David Lambiotte's before, during and after his stay in Vietnam, Harry Holland will testify to David's behavioral changes, increased stress, irritability and other emotional changes. 18 Milford Rd., Newport News, Virginia; As David Lambiotte's brother, Michael Lambiotte will testify to David Lambiotte's emotional and behavioral changes, increased stress and depression since his return from Vietnam. 11 White Oak Drive, Newport News, Virginia; As David Lambiotte's high school friend, after spending time with David Lambiotte in Vietnam and after being David Lambiotte's roommate after Vietnam, Richard Scott will testify to David Lambiotte's attitude, behavior and emotional changes, his increased stress and his depression. Melbourne Beach, Florida. As David Lambiotte's neighbor and friend before and after Vietnam, Henry Sadler will testify to David Lambiotte's behavior and attitude changes, his increased irritability, depression and stress. 97 York Street, York, Maine; David Lambiotte's treating physician will testify to David as scientist and toxicologist; chief toxicologist for the Environmental Defense Fund; Research scientist in Reproductive Toxicology for National Institute of Health; general causation expert on the extreme toxicity, neuro-toxicity, reproductive toxicity, and carcinogenicity of Agent Orange and TCDD; mechanisms for the male-mediated birth defects; specific causation on the birth defects of Kerry Ryan, and Michael 15604 V. A. 48 William T. Thompson, Ill* James Gutshall William J. Ezzi John Flite and Chad Jordan, was related to and caused by their respective fathers' exposure to Agent Orange in Vietnam; see curriculum vitae, all summaries, with references and documents attached; deposition testimony in possession of all parties. Direct examination estimated 1 day; Cross examination estimated 1 day. Mr. Thompson, Theresa Buckley, Leo Crivello, Mr. D. Hallek, Cecil McGill, Dr. Ernest Valasco, Dr. A.J. Reichas, Dr. Raymond Simpson, the custodian of records, American Mutual Liability Insurance Co., St. Louis, Missouri, Contracting Officer George Collins, Contracting Officer William Fenner and Mr. Thompson, are all witnesses relative to Thompson Chemical Corporation which the defendants reserve the right to call as witnesses in their case in chief; a page and line summary of Mr. Thompson's deposition will be provided in the event the plaintiffs do not wish him to testify as a live witness; the others, having not yet been deposed, remain to be determined. 6307 Jackson Street, Philadelphia, Pennsylvania 19135; will testify to his observations concerning the actual spraying and defoliation of Vietnam; he is a veteran who travelled extensively in defoliated areas; total time of testimony estimated at 2 1/2 hours. 833 4th Street, Camden, New Jersey 08103; will be asked to testify to identify photographic exhibits and as to his observations of defoliations in Vietnam. He is a veteran who was there during the spraying; estimated time of testimony less than 1/2 day. 6544 Windsor, Philadelphia, Pennsylvania 19142; a former helicopter crew member will testify concerning the defoliation as it 15605occurred; estimated total time of V. A. 49 testimony 1 1/2 hours. Major Lawrence Hondich 212 Flynn Drive, El Paso, Texas; will be asked to testify concerning the defoliation process and to identify and explain aerial and other photos of Vietnam during the defoliation. Anticipated length of testimony less than 1/2 day. Ret. Mstr. Sgt. James Gregory 5561 Wadsworth, El Paso, Texas 79924; will be asked to testify to his observation of the defoliation process as it occurred in Vietnam. Anticipated length of testimony 1/2 hour. William J. Eaves 10207 Summer Road, Philadelphia, Pennsylvania 19116; will be asked to testify to his observation of the defoliation as it occurred in Vietnam when he was present; expected length of testimony 1/2 hour. V. A. 50 safety of the plant, the spokesman in labor grievances at Nitro and acknowledged that his objective was to produce as much 2,4,5-T as possible. Agreed that when Monsanto began producing 2,4,5-T for sales to the Government, certain quality speicifications were most entirely relaxed and there were subsequent gains in rate. During his tenure at Nitro, Dotson was concerned about the health and safety of his workers at the 2,4,5-T plant. However, he never attempted to find out any more about dioxin - all he knew was that the 2,4,5-T did contain dioxin, although he knew that dioxin was toxic. During his tenure as Production Supervisor, the amount of 2,4,5-T being produced significantly increased and when hel left, there were three shifts per day producing 2,4,5-T and the plant was producing that product 24 hours. Transcript of November 2, 1983; p1 1,116&12;p12,116-12&22-25;p13,112- 5;p l 4 ,112-8&17--25;p15,112 --5&7 -- 17&19-- 2 5 ; p 1 6 , 1 1 1 - 2 3 ;p17 , 113-9&13 - 1 7 ;p18,11 1-2&17--25;p 19,1112 --14;p21,111 3-18;p2 5,115-11;p26,118-9;p28,1116-23;p29,l 16-22;p31,111 5-18;p34,1122-25;p35,11 10-- 12 ;p39 ,111 --8 ;p41 ,112-25;p 4 3 ,1115- 2 5 ;p44,111 --5 ;p46,111 7--19;p47,111 --15; p51 ,1116-19; p5 2,115-8; p5 4,1119-21 ;p5 7,1117-24;P58,1110-23;p59,1120-22;p6 0,1116-25;p61,111-25;p6 2,111 --14;p6 3, 1 1 2 - 2 5 ;P 6 4 , 1 1 1 - 6 ;p65,1 1 1 3 - 2 5 ;p66,111 - 4 ;p67,111-2&15-25;p70,119-11;p71,ll &9&29II1-;,,;1p2-I4p,1318-11881-1,64--511-222213;;&211p1p5-523,1912361-1;,-;-&11-1;pp021;1p6p310819122471-21;9;,,;4;1p161pp004,-p10183,1912,-17&111,2021551211-11;4-,7,1,21P15172-;,12&1111P11-;113p2-2049591-41-1&---3-22-792-171217;4,2&357;p815,0;p3&1;&1p81;;,-17p1pp11212627811--17191-,534021,11--65;1,&2-21p480,,1218114915;-,1136p1--120;5;21p-p111,5;-;8141p82p9111;&-1p--11951;8-22ip1122,;38,1251p891184,,11;-1H81,-;0;21p61p1p2,8811715-11-14,115,-12;0-11;l1,80p2p54616ll7 --2 4 ;p1 29,113 --14 ;p 1 3 1 ,1 1 2 -2 5 ;pp132-13 2* . - t^ V. B. 2 Verne Rhodes 9;p140,ll1-6;p142,ll16-20;p143,ll1-5 2120 Windport Lane, St. Louis, Missouri. Verne Rhodes born April 6, 1939, is a present Monsanto employee having been so employed for the past 22 years. He received a Bachelor in Chemical Engineering from Georgia Tech and a Master of Business Administration from West Virginia University. His present position at Monsanto is Manager Markets and Products, Paper Resins. His yearly salary is $61,000 plus benefits. In April of 1966, he became Production Supervisor of the 2,4,5-T plant. Buildings 92 and 51 were combined. He was Production Supervisor for a 3 year period and went into the 2,4,5-T plant about eight hundred times over the years. He terminated the position in April of 1969. Answered the esterification process of 2,4,5-T did not take place at Nitro but at Krumrich where it was thereafter shipped. The product when it left Nitro looked like a brown powder with various size grains, some finer than sand, some larger than sand with a hydrocarbon smell. The first time hears the word dioxin is in the 7 0 's and probably in 1977. He became involved with herbicides as an Assistant Production Supervisor in 1963 or 1964. Recalls meeting with Udell when Udell showed him a glass vial and indicated that it was highly toxic. Udell mentioned that he had been given an analytical technique by Dow. The chlroacne that -he saw was much more severe than pimples. Many people that worked around the Nitro unit had it on their face so prominently that it would look like their eyes were permanently blackened. Pimples on the workers. He had seen chloracne lesions under the skin as large as his thumb. 15608 V. B. 3 Postules were present on some of the people who had the chloracne. Hearing how toxic dioxin was from Udell, he has no recollection of doing anything to investigate the extent of that toxicity. Never recalls researching either by experiment or by reading to ascertain further information on dioxin. He never heard the word dioxin being used at Monsanto all during the 1960's. Dioxin in the 2.4.5- T was a major concern of his and his people were worried about trying to eliminate it. Although he was concerned for the workers1 safety, he was not concerned for the consumers. Never remembers asking a worker with chloracne if the worker had any other medical problems, nor does he remember reading any medical reports in which worker problems were claimed. Agrees that at one point almost every worker at theT plant had chloracne. Nitro had five customers of 2,4,5-T acid. These were the larger chemical companies. Customers included Ag-Chem and their Krumrich plant. He doesn't know whether there is any safe level of dioxin in 2.4.5- T. Does not remember the size or the frequency of the lots being tested for dioxin. Mr. Rhodes got chloracne in the fall of 1966 and he has had it for almost eighteen years and still has it. Agrees that in January of 1969, Monsanto still hadn't solved the problem of getting the dioxin out of 2.4.5- T. Transcript of February 17,1984; p5,119-25;p6,111&21-25;p 7 ,111-6&18-2 5 ;p8 ,111 --3 ;p9, H5-25; pi 0,111 -5&21 -25 ;p11,111-9&21-25;p12,111-15&21-25;pi 3.111- 3&11--2 5 ;p15,116--2 5 ;p16,111-3&6 -25;p17,111-2&8-9&13-24;p18,111--2 5 ;p 19,111 -- 15&18--2 5 ;p20,113--8&11--2 5 ;pp21 -33 ;p34,111-12&21-25;pp35-36;p37,111 -5&19-23;p38,ll6-23;p40,1114-23;p44, Il15-20;p59,1118-25;pp60-79;p80,111 - 19;p83,ll14-25,p88,l8-25;p89,ll1-2;p 90.111- 16;p92,114-25;p93,111-3&20-25 V. B. 4 Dexter Sharp ;p94,ll1-4;p95,ll5-15;p97,H3-12;p10 1 ,1H7-21 ;p102,1123-25;p103,111-21 ;p 104.111 2-25;p105,111 7-25;p106,111-23 ;p107,111-16;p108,113-7;p109,111 9-25 ;p111 ,114-7 ;p1 12,119-25 ;p1 12,1 H - 4 ; p 114,117-21;p 116,111-7&11--24;p 117;p 11 8.111- 9&22-25;p1 22,115 --2 5 ;p123,111 --2 0 ;p1 26,114 --25;p12 7 ;p128,111-13;p130, 1116-22;P132,1115-25;pi 33,111-4&15-2 5 ;p134,111 --13;pp135 --137;p138,111 --6&1 7 - 2 5 ;p13 9 , 1 1 4 - 2 5 ;p14 0 , 1 1 4 - 2 3 ;p141,11 2--2 5 ;p142,111 --2&19--2 5 ;p143,111 --22;p1 44.111 --1 5 ;p148,112 --13 ;p14 9 ;p150,111 0 -25 ;p1 51 ,H1-18;p152,ll21-25;p153;p1 5-1, 11461.43&15.111- 1218-15- -2;2p0111;3;p7P;12p16,1517651,,41111,111-3111-1-79-1.;42p&;1p168196-,221,511;2p1-12660;5-p,2115711;3p 13042 Weatherfield Drive, St. Louis, Missouri: Dexter Sharp is a present employee of Monsanto having been so employed for 33 years and possessing the present title of Director of Environmental Science Formulations. He is a Ph.D. in Chemistry. Salary $86,000 per year. In 1963 he became Group leader in the Agricultural Division, working under Dr. Stephens and Dr. Speziale. He was a Group leader to 1968. His resonsibility was to direct a group of Chemists in Process chemistry developing technical chemical basis for manufacturing the proess which comrises all the conditions necessary to obtain a final product. Dr. Sharp was working on the 2,4,5-T Research Project in 1964 1965 and learned about the presence of dioxin in the 2,4,5-T from Dr. Stephens. Dr. Stephens told him that dioxin was a very toxic material. He heard at that time that a certain amount of dioxin would kill half of the test animals at a certain dosage and therefore Dr. Stephens told him it was highly toxic. Other than looking up the word chloracne in a dictionery he never did nay research or investigation of any kind in connection therewith. The workers were paid a premium to work at the T plant beause of V. B. 5 13610 potential chloracne problems. When he was told by Dr. Stephens that the impurity was dioxin, he knew that dioxin was highly toxic. Felling from that day until the present time has not changed. He was thereafter given a sample of dioxin from Dr. Stephens. Dr. Stephens also told him that dioxin was a toxic material. He was William Udell's superior. Acknowledges that Monsanto knew in 1965 how to analyze dioxin content T acid. Knew that Monsanto was selling 2,4,5-T to the Government in 1965 and he knew then that that 2,4,5-T contained dioxin. He agreed that dioxin was a highly toxic impurity in animal oral tests. At that time they were sellng T to the Government, which they knew contained dioxin, he knew of animal tests that resulted in death to the animals. Knowing the above, he nevertheless did not tell the Government that there was dioxin in the Agent Orange because not being a toxicologist, it wasn't his responsibility. He did not know whether it was someone else's job to tell the Government. He also didn't tell the Government because he had no contact with the Government and he would not have known to whom to speak. However, if he had known with whom to speak in the Government he still would not have told that person that the Agent Orange contained dioxin. Until March of 1968, neither he nor those working under him had recommended any procedures in the manufacturing process, that would eliminate or reduce dioxin in the T acid. As one who attained a Ph.D. in Chemistry, who taught graduate and undergraduate students chemistry in college and who geared his career in chemistry, he was not able to name any chemicals made by man that had a greater degree of toxicity than dioxin. 15611He reported the results of his V. B. 6 John A. Stephens analytical proedures indicating the amount of dioxin to John Stephens. Sharp's Research Group analyzed the dioxin content of samples of Monsanto's final batches of 2,4-D. He was aware of the animal toxicological tests which revealed that dioxin was highly toxic to animals and perhaps to humans. Transcript of October 20,1983; p35,112-16;p42,117-14;p47,1119-48;p4 8 ;p50,111 6-25;p51,111-1 2 ;p54,112-18; p58,116-25;pp59-87;p88,111-23;p89,13 ;p95,121 ;p96,ll4-23;p100,H5-9;p105, 114-21;p1 07,117--25 ;p108,111 7-- 19;p112 ,111 1-25 ;p1 16,111 4-16 ;p1 17,111 5-18 ;p 128;pi 30,17;p136,1115-21 ;P 146,114-8. 800 North Lindbergh Boulevard, St. Louis, Missouri Mr. Stephens is presently employed by the Monsanto Company as Director of World Wide Operations for the Agricultural Products Company Research Division. He received a Bachelers, B>A>, and Masters Degree in Chemistry and a Ph.D. in Organic Chemistry. His present salary is $86,000 per year plus benefits. 1961 to 1963, he was the Group leader in Process Research in Agricultural Division and from 1963 to 1969, was the Manager of Chemistry Research. 1961 his position was Group Leader Process Research. He was required to supervise the activities that were going on to support the manufacturing proess. Their goals included the attempted reduction of manufacturing costs, job operating problems to solve quality problems in relation and packaging problems. 1963 he became Manager of Research for Chemistry. At that time Dexter Sharp became group leader working under him. 1964 or 1965 it was called to his attention that dioxin contained in their 2,4,5-T. They received a letter from Dr. Kelly. When Dr. Kelly sent Dr. Stephens a sample of dioxin, at that time he was informed that dioxin was highly toxic and was 15612 V. B. 7 warned to take certain safety precausions when handling it. He was told not to touch it with his bare hands. The Medical Department had an obligation to test for toxic effects an they normally would inform Research of the test results. They had an obligation to tell Research about any toxic effecs. Test them and tell them the effects. If a product that Monsanto manufactured had a toxic impurity, two different organizations, research and manufacturer had an obligation to attempt to remove the toxic impurity. Research would tell manufcturer what was wrong and manufactureer would hopefully attempt to do it. Howver, they weren't successful in cleaning up the 2,4,5-T process for a number of years. At the same time or within a few days thereafter he got the dioxin sample from Dow. He also had received the Dow analytical proess. Dr. Kelly stated that the analytical process was received by him from Dow. He then gave the Dow method and Dow sample to members of his research staff with instructions to analyze it. Monsanto thereafter developed a method of analytical determination of dioxin in the T. With respect to the analytical process within less than a day they were able to find out whether a particular lot produced contained dioxin and to what extent. He contined to have discussions with Russell, the Director of Product Quality Control from 1963 to 1974 to inform Russell as to what was happening in his research. Stephens acknowledged that if the temperature were higher, that would result in a grater amount of dixoin. Further agreed that the dioxin concentration in the autoclaves was highly sensitive to temperature with a slight increase in temperature 15613resulting in a significant increase V. B. 8 of dioxin. Acknowledges it was Mr. Udell's responsibility to supervise the project to reduce the dioxin in the T. Never had a knowledge or realization or belief that there was a safe level of dioxin in the 2,4,5-T acid and Monsanto was never operating under a type of maximum dioxin level. As of September of 1965 Monsanto had an analytical process to determine the dioxin content of the T. Acknowledges that they anted to reduce the dioxin content at that time because Dr. Kelly of the Medical Department stated that the contaminant was toxic. He reeived that information directly from Dr. Kelly and disseminated the information through Reseach. Kelly told him that he had been to a meeting at Dow. That Dow had agreed to give Monsanto the analytical method and a sample of dioxin. It was his feeling that the reason that Dow was doing that was that "it had something to do with the whole picture that was around Agent Orange." Acknowledges that at the time of the Kelly discussions he knew that the T acid that they were selling was going into Aget Orange that was being used in Vietnam. Assumed that the product was going to be sprayed by aerial spray or by hand and it was Monsanto's assumption that it would be sprayed both by hand and through the air. The method by which Agent Orange was to be applied in Vietnam was not considered in any determination as to whether or not or what they should hae done with respect to the dioxin in the product. Also the existence or non-existence of that dilutent in Agent Orange never influenced him in any manner with regard to his actions in connection with the dioxin content of the T. It was Mr. Speziale's communication that first prompted him to reduce the dioxin content. 15614Speziale's V. B. 9 conversation - he told Dr. Stephens that he received information from Hr. Arvan or Mr. Rumor, the commercial people that they wanted the material eliminated because it as toxic. Speziale told Stephens about what was in the literature and they looked through the literature. He and Mr. Speziale went through the chemical literature, found a couple of references, one in German. Assumed that the greater the dioxin content, the greater the potentiality for hazardous effect and that assumption has never changed.Assumed that. AGent Orange being used in Vietnam would come into contact with some people. Knew in 1965 that their product had dioxin. Knew that the product was being sold to the Government. Did not tell the Government or suggest the Govt, be notified. The reason he did not suggest the Govt, be notified was that he had no contact with the Govt. Then says that the reason that he did not tell the Govt. that the product had a toxic component was "because it was someone else's responsibility." He did not know whose responsibility it was nor did he ever inquire as to whose responsibility it was. Acknowledgd that the butyl ester of T was contaminated with dioxin and the intermediate products were contaminated with dioxin as well. Stated that Dr. Kelly said worker contact with the intermediate products presented a hazard to workers and he believed Dr. Kelly, workers in the 2,4,5-T facytory had safety shoes ad safety gloves and safety glasses to avoid contact with the 2,4,5-T and intermediates that were contamineated with dioxin, in order to prevent worker harm from the contaminated 2,4,5-T it was suggested that they wear protective clothing. He acknowledges that when the workers came into contact with the end product they still are required to maintain the same safety 15615 V. B 1 0 equipment, however, he was not concerned with what happened to the people coming into contact with the product after it left the hands of the workes, although he agrees that there was knowledge of worker harm up through the final stage of the manufacturing product. The end product still contained dioxin. The end product was as contaminated when it left the factory as it was when the workers had to deal with it on the prodution line and the only reason that he did not inform anyone else of the toxic problems with respect to the end product was that he as not an authority on toxicity. The only authority in the company was Dr. Kelly but he never spoke to Dr. Kelly about the problems that could be caused to the ultimate consumers. Agreed that if you increase the temperature, you ncrease the dioxin and if you hold theproduct in the autoclave longer, you increase the dioxin. He assumed that although there is a worker problem there is not aprospective customer problem because noone had ever told him it was a problem and he doesn't remember whether anyone told him it wasn't a problem. Agreed that chloracne resulted in tiny bumps. However, assumed that dioxin exposure caused a few bumps and nothing more. Kelly told him that chlorance meant a few bumps on the skin. Never asked the cause of chloracne nor did he ask how long chloracne lasted. Never researched or questioned about chloracne. Never assumed the Government had a process to test 2,4,5-T for dioxin, nor did he receive from the Govt, any indication that they knew that the 2,4,5-T that Monsanto was selling to the Govt, had dioxin. In the Kelly letter that informed Dr. Stephens about dioxin, kelly told them that it was a very toxic material that should be handled with caution. 15616Dr. Stephens never V. B. 11 attempted to find out anything about the toxic effecs of dioxin at any time up to 1973. Claimed that Russell, the Director of Quality Control determined which lots of T were to be tested for dioxin content. He had no reason to disbelieve that in 1968 he was averaging 40 ppm in he T acid. As a consequence of Dr. Kelly's letter, he treated dioxin as a highly toxic component. Agreed that during the time he was attempting to reduce the content of dioxin of T they continued to sell to the Govt and realized in 1965 that the T that they were selling to the Govt, was going to be used in Vp4T9-2-2-7111-71111111;,;,;,24i1p121-18pp,120-2151,3;763r11211e1;8p11-21241314,a;,;-7;p11t61131pp21-p--261,13n8,;;;,11n1&6;p11p1p11969--141-3;-,;sp1a152p11Hp1012109,3411,;;c0,1m11191ppp19281l7,54-;3;1;r513.11,411p11p;2-31705i-1;;-,,,l5p11pp41p302l1;132884-l-ll,,10l-p614l1111425t10;,21113,;4211p&&HP6--11625-312,;;;;4,,3121p1p1pp011111469-5;,;3-16p;1p1-825120,4191526;--,3;p1121p41o--1152l51-181p&5;1;&141201p2p6232f,483;,,;,2,-69191pp21266141;1048,57-;;0p-1111,pp412,2--1151-;,2;;;,1l1iP111411p2p1-p96047149,1,1252164O249161073517;;,0-1;e2&5p11pp11--1-16,-517,5;7;91c01;11131p1215p131,;2;-,t,9,p--1p1p543201521o1--5581;;l22;11pip&&8215--l112b2213;;;6p-1115p10p6p&9718e09;24,,,22111;p&i11186r56-16,;;05;--21181p11p4p&6212216--,,8--;,150p1i1210p9321234154321,1,8&115,12&3,3171113,350;;;--&l11120p;1pp1--18116111,l,;;2;1p111231pi-11p121-237p5,52;012p11-2114521--28---50,7,;--8;211511pp12242-p2411210;;-;,l41191ippp,2029581,2552;;,;-,21;18pp1lp6112;-31-,165;;p;4;&1p11l1131252ppp3p177,1;;7;,1511616193ppp01i9i0;82,,pl7, 82,l6;p184,l20;p187,ll16-22;p190,ll7 -13;pi 91,1116-22;p192,1114-25;p193,1 121-25;p1 94,111 -23;pp1 95-1 9 6 ;p205,11 2&6-11 ;p206,H1 3&21-24;p207,l1 ;p208, 118-10 ;p209,111 -21;P218,ll5-25;p219, 155517I1&21-25;p220,l1;p221,11-9. V. B. 12 William R. Udell 60 Tealwood, Creve Coeur.Missouri Mr. Udell is a present employee of Monsanto Co., having been so employed for approx. 35 years. He received his B.S. and Master's Degree in Chemistry and in 1960, was employed by the Agricultural Division Research Department. Author of several documents in connection with attempted improvements in the 2,4,5-T process. First heard about dioxin in the mid-1960's and agrees that the acute toxicity of dioxin cannot be overly emphasized. His understanding of the word toxic means to cause death. He recommended to employees that they wear safety glasses and gloves and a face shield to minimize expousre and to avoid thepossibility of causing death when in contact with dioxin. Agreed that the incidence of chloracne was almost universal with workers engaged in the 2,4,5-T manufacturing process. Knew in the mid-60's that problems similar to Nitro and Badische occurred with other manufacturers. Knew about Dow's analytical process to determine existence of dioxin in T and received it in 1965. Analyzed samples of the 2,4,5-T manufactured during the 1950's and ever since the late 5 0 's claimed that the dioxin content then averaged 10 ppm, but in 1965, averaged 50 ppm. Believed the dioxin formed almost entirely during the period in the autoclave reaction. Felt that because dioxin killed animals it had the potentiality to kill humans as well. Knew that the Govt, was buying Monsanto.'s 2,4,5-T. He never prepared a procedure for the analysis of dioxin in Monsanto's T and does not believe that anyone else in Monsanto did so either. Acknowledges that dioxin content in 1965 was 35 ppm in 1968 36 ppm and about the same through January of 1979. V. B. 13 15618 using it. He was repsonsible to put the cost factors for Orange together and then recommend the price. Acknowledges that the Govt, had promulgated rules restricting 2.4.5- T in lakes, ponds, ditch banks or drainage ditches - don't go near susceptible crops and liquid formulations not to be used around a home and recreational area. Thinks he learned in 1969 that his 2.4.5- T acid had a dioxin impurity, but never told anyone. Acknowledged that dioxin was toxic but never attempted to find out the end level. Has no idea of the dioxin tolerance, although assumes there was. When he knew in 1969 there was a toxic impurity in the product, it was then he went to Cecil Russell. Russell told him that they had a procedure to analyze 2,4,5-T for dioxin, but does not recall the ppm specifications. Believed Monsanto was testing 2.4.5- T for dioxin in 1969, but never saw the test results. He relied on the peole who delivered the product, but never knew how the product was made - he never worked at the plants. Never knew how much dioxin they had in the product. Never asked about an analytical process to determine dioxin because it wasn't his job to ask and never asked whether they had a process to remove the dioxin because that wasn't his job. Hears in 1964 or 1965 - worker health problems in 2,4,5-T plant. Transcript of May 3,1983 p 6 , 123;p 9 , 1 1 6 - 1 5 & 1 7 - 1 8 ;p10 , 1 1 1 8 - 2 0 ;p 111 218,8. 11-121115-5; p-222&111,;21p-111513,- 1;1p1711;9p22,-1311,551;-1p821&6-11,691-&1112713;--p212420;;p,p1 24.112- 4&20-21 ;p25`,12;p27,112-1 1&14- 16;p 3 0 ,111-8;p34,ll12-19;p36,l6;p38, 1 1 6 - 1 1&15 - 1 6 & 2 4 - 2 5 ; p 3 9 ;1-12 & 2 1 ;P40,1 7;p41,1115-25;p42,111-10;p50,111 8-21 ;p 5 1,111--6 ;p54,111--18;p58,118--17;p59 ,113-25 ;p60,H4-8&1 5-23 ;p61 ,118-22 ;p 62,111 9-23;p63;p64,111-8;p72,111 5-18 ;p 7 3 ,111-4;pp74-75;p77,1123-25;p78,l 11 -3 ;p79,119-1 2&1 6 ;p82,H6&1 6-25 ;p83 V. B. 16 James E. Springgate ,l8;p85,H2-19;p86,ll10-19;p90,111923;p94,116-1 1 ;p95;p96,ll1-15;p97,H4 -2 5 ;p98,111-7&16-17;p101,113-7;p 104, 111--2 ;p105,111 0--2 5 ;p10 6 ;p107,111 --24; p 108,1111-18;p110,18;p111,119-12; pi 1 3,17&11 ;p114,122;p117,I5;p118,114;p1 20,1120-22;p126,111 1-13;p127,111-6;p 128,1119-23;p129,11;p14 0 ;p148,1119-2 4;p 151,H18-20;p153,1113-15; pp 157-15 8 ;p159,113--4 ;p160,117 --8 ;p162,1116 --20 ;p16 3 ;p170,114;p173,1122--2 5 ;pp174--17 8;p 179,111 --12;p180,112-8&17-25;ppl81 -- 183;p184,111 --18;p190,113 --7 ;p191,111 4 - 2 5 ;p192,113 ;p193,121 ;P 195,1122-25 ; p 196,111 --13 ;p200,116 --19 ;p201,112-15; p203,1124-25;p204,1 1 ;p206,1124-25;p2 07.111- 19;p209,111-5;p2 11,111 7-15;p2 12.111- 13;P219,1111-21&24-25;p220,11 1--8&17 --2 3 ;p224,111 7--19;p225,11 8 ;p226 ,1110-25;p227;p228,111-16&21-25;p229 ,111-13;p232,1 1 3 - 2 5 ;p233,111-16 & 2 5 ;p 235,111 0-1 1 ;p236,H27-19;p244,l1 ;p24 6,1117-19;p255,111 5-- 19;p258,1122--25; p259;p260,111 --19;p261,125;p264,112425;p265;p266,ll1-4;p268,111 1-16. 13060 East Sunset Drive, Los Altos Hills, California: James Springgate is a present employee of Monsanto and is the President of Monsanto's Electronic Materials Company. He has been employed by Monsanto for the past 34 years and originally transferred to Nitro in 1962 as the Manufacturing Superintendent of Organic Division Products. He was the Plant Manager of the Monsanto Plant from 1964 through 1968. He became involved with herbicides in 1964 and his overall responsibilities as Plant Manager included personnel safety, labor relations, service facilities maintenance and construction for the entire plant. He recalls having 700 to 800 employees. His responsibilities included reviewing with the superintendent of personnel the medical doctor and the safety director, worker health problems. The medical doctor was Richard Wallace. Met on amonthly basis during the time that he was Plant Manager to X 1/ v> V. B. 17 J discuss medical complaints of the workers. Has a recollection of workers complaining about health problems other than a skin condition but doesn't remember where that came from. During the time that he was there, the chloracne problems in 64-68 were decreasing from the prior four years. The total of the chloracne problems for the four years before he got there was greater than for the four years he was there. He continued to have conversations with Dr. Kelly one to two times per year concerning worker health problems in the 2,4,5-T plant. During 1964 to 1968 reviewed approximately 100 medical files of 2.4.5- T workers who had chloracne during that time. Does not remember whether the 100 workers with chloracne had other complaints as well. Knew in 1964 that the 2,4,5-T was being sold to the Govt, for use in Vietnam but did not know whether it was going to come into contact with American soldiers. Hears about dioxin and heard that it was a highly toxic impurity in Monsanto's 2,4,5-T but does not remember when he heard it. It was the responsiblity of the AGricultural Manufacturing Management Team to eliminate a toxic content from a product. 2.4.5- T workers were getting paid extra for working in the Plant because there was a high incidence of chloracne among the workers and many workers did not chose to work there. The additional wages were an incentive for the workers to work. Although claims not to recall whether he was ever told during the time that he was at Nitro that dioxin was in the 2,4,5-T. Transcript of October 27, 1983. P 5,ll15-22&24-25;p6,8-9&17-24;P7,111 -1 7 ;p8,1123-25;p9,111-9&11-13;p10,11 2-5;pi 3,111 -6;p14,15;p15,111 8-24;p16 ,1113 --17;p18,112--4& 6--7&9 -- 19 ;p21,119- V. B. 18 15621 Jack Strum 4p75p122-9211;,,1p21&11-5,168;;;121pp1p120.3;572121p184-614;,,2211-21p-023-;,-2215-p111132;,,11151pl41,1655;911p488;1-;;;;,;p1pp1pp1151--,p1221230659177,1851861---139;,831p11;&1,,,;-;,p111,1pp3612172l28111851;39-l;39p6p5116-2;;0,-2,1Pp26--2-0;2H,&57113p5125;-5&2p18&014216,,;-115647p;25,6,421p1-11,2;4-1;1&211p31p1825-,118151-2271-32,1&2119-1,5;29-1711p,59-212;-,1&1p52-6121;;5112p2p-512-210-;125-22p3821,;1;65p;P1-613524,-p11138-;16;;,;,83p2p51plp1994,l0-221,34171,;;1811p1,;p61471--&11p135168;,,;211116p39-p-61;112123p-05-77,,1122775112-;,-; 712 Short Spoon Circle (city and state not available through transcript): Jack Strumm was a Monsanto employee from 1965 to 1970. When he was hired he was hired at Nitro, West Virginia and his position was Technical Service Engineer, his responsibility was to carry out projects assigned by the Group Leader, normally involving improvements in rate, quality, yield and other processes. In 1969 he became Production Supervisor, initially for 2,4,5-T. His obligation included a responsibility to increase the production of pounds per hour of 2.4.5- T from the years 1965 to 1969. Met with Vernon Rhodes in the summer of 1964 or 1965, with regard to 2.4.5- T. Does not remember from whom he first heard about dioxin. Thinks he first heard late 1966 or 1967. He, himself, had contacted chloracne, had it primarily on his face for five or six years. He has no knowledge of anyone missing work because of chloracne. When he heard about dioxin he eventually began a series of experiments for the purpose of reducing the amount of dioxin. Never attempted to learn as much as he could about dioxin. Acknolwedges that dioxin was V. B. 19 15628 contaminant in 2,4,5-T. Contaminant dioxin developed in the process at some point before it left the 2,4,5-T plant. Their studies indicated that high temperatures and long time periods at those temperatures tended to increase the amount of dioxin in the trichlorophenol. He first learned of dioxin contamination in the T shortly after learned about dioxin. The pressure was basically controlled by the temperature and if you increase the temperature, you proportionally would increase the pressure. The lower the temperature the slower the reaction. The dioxin level was much lower the latter part of the 1960's. There was a time that Monsanto attempted to speed up the manufacturing process in order to meet requirements. This was sometime around 1967. He had no thought of whether to be concerned or not with dioxin to the end user, his concern with dioxin was to the people who worked in the 2,4,5-T unit. He did not know of anyone who had an obligation to convey the fact that dioxin was the contaminant in the 2,4,5-T which was being sold to end users. Toxicity to him means poisonous and poisonous menas that if you ingest it it will kill you. His recollection is that they had no analytical method to determine dioxin content until 1967. Did not share information regarding the Monsanto's process to reduce dioxin with anyone in the Govt. Transcript of December 16, 1983: p 6 , 1 1 5 - 6 ;p7,1 1 1 - 1 3 ;p8,111-8;p9,116-8 & 1 4 - 1 7;p10 , 1 1 8 - 2 5 ;p11,1 1 3 - 6 & 2 3 - 2 5 ;p1 24p637-1, 21.-45.,, 21111117&51111&,12H1115-;24p--23-55-24-;-2;39p2155p5&;353;;5p;8pp6&;p31-p42,5,227211640541;81,;,p1;-1p1,121p11312-1951119-53,11--;;,,14p1p1-81124;215;11p4p81;4-1p43;,-,1p-115658343111,;, 1p;;4112;pp12p-,1321129651-511;2-,2-,1,1p145,1141211;;11p&p6-9195241,5-1-15-2-4552115;5,-,p4&91l11;;3l2p1;811pp512-;3i2 V. B. 20 A. John Speziale -5 ;p57 ;p59,111-9&16-22;p61,111 6-2 1 ;p 62.111- 6&15-25;p63,111-6&13-18&25;p6 4.111 - 8 ;p65,116-25;p66,111 -22;p67,H 23-25;p68,111-6;p70,125;p69,111 7-19; p 71,111--5 ;p72,111 2-15;p74,1122-25;p7 6.111 -11&14-17&20-24;p77,112-25;pp78 - 8 0 ;p81,1 1 1 - 4 & 1 7 - 2 5 ;p82,114-19&23-25 ;p8 3 ,111-4;p89,111-3 ;p 9 3 ,111 7-25;p94 ,111-21 ;p95,ll20-24;p98,H21-25;p99, 114-6;p101,118-11 ;pi 03 ;pi 04,111-5&8- 2 5 ;p105,113-11 ;p106,112-25 ;p107 ;p108 ,111-18;pi 09,115-11&20-25;pi 10,114-2 5 ;p 111 ;p 112,111&6-12;p113,1121-25;p1 14,1112-20 ;pi 15,113-5&13-15&21-25 ;pi 16.111 --8 ;p 118,116 --23 ;p 120,115-1 6 ;p 12 1.1110- 11&15-25;p122,111-16;p123,111 0--13;p124,111 6--25 ;p125,111 --10&18--25 ; pi 26,111-10&17-25 ;p 127,111-8 ;pi 28,11 16-22;p133,1120-25;p13 4 ;p135,1120-25 ;pl36,111-4;pl42,111-10&14-18 ;p145,1 110-18;p146,1111-16;p147,114-25;p148 ,1114--2 5 ;p149,111 --16;p151,111 2--22;p1 54,1118 --2 5 ;p155,113-16;p156,112 -- 10 ;p 160,114-25 ;p161,111-7;p163,111-7 ;pi 6 4.1111- 2 5 ;p165,111-4&20-24;p 171,1123 --2 5 ;p1 72,111 --2 3 ;p175,1114--19;p176,11 5-16 ;p 177,111 6-25;p178,111 -2&20-25;p 179.111-- 2 ;p180,116 --17;p1 81 ,111 5-1 9 ;p 184,ll24-25;p185,ll1 -20. 311 North Umberland Avenue, Redwood City, California 94061 : A. John Speziale was the Director of Research of the Agricultural Chemical Division from 1963 to 1979 and was employed by Monsanto from 1948 to 1979. Mr. Speziale is presently a consultant to Monsanto. Paid pursuant to Contract, receiving $500 per day guaranteed, 8 days per month. He became Director of Research in 1963 and first became aware of the dioxin impurity in 2,4,5-T around 1965. When he heard about it he gave Mr. Udell, a chemist, instructions to go to the literature and find out all he could about the compound and structure formation toxicity and to find out what the company knew about it. When he learned about dioxin he was told that it was a toxic substance and he considered as a priority matter to find out about dioxin. V. B. 21 f Thereafter, he realized from the Chemical Literature that dioxin was highly toxic. In accordance with his instructions, either Sharp or Udell developed an analytical method to determine the presence of dioxin in 2,4,5-T. From 1965 to 1970 Mr. Speziale reported that he informed the Monsanto Operating Committee of his progress or lack of progress in reducing the dioxin content in 2,4,5-T. The Operating Committee consisted of various department heads or directors. Around 1969, he wrote to Prof, Baldeshweiler in Washington, forwarding to him Monsanto's analytical methods for the detection of dioxin. Prof. Baldeschwieler was an advisor to Dr. Lee DuBridge, the President's Science Advisor, whose testimony clearly infers that the Govt, did not have a dioxin detection analytical process at that time. Dr. Baldeschweiler was the sole outside person that Mr. Speziale communicated with concerning 2,4,5-T during the 1960's. As the Director of Research, his responsibility was to administer and manage the research in the Agricultural Research Dept, which had about 120 people. From 1963 until 1970 he communicated with Dr. Kelly of the Medical Department, approx, one per month, in which Research forwarded written summaries of anything having to do with toxicology. When he received the assignment in 1963, Dexter Sharp and Bill Udell were the leaders in connection with resolving the problems with the T process. The work on the project went on until 1969. It was from one or more of his Research chemists that he first heard the word dioxin. Says he found out in 1966 or 1967 that it was highly toxic. Probably learned in 1964 to 1965 that Monsanto was selling 2,4,5-T to the Govt. When he found out that dioxin was highly toxic, that is when he told the research section to get it out of the product. In August of 1969, Monsanto discontinued the production and sale of 2,4,5-T. Always agreed with the statement that the concentrations of dioxin in the trichlorophenol was equal to the concentrations of the dioxin in the 2,4,5-T acid produced from the trichlorophenol. Probably heard in the early 1950's that the workers in the 2,4,5-T plant in Nitro were receiving more money than the other workers, because it was a more hazardous operation in the T plant. Never attempted to determine if there were any worker problems in the T manufacturing process other than chloracne. He knew in Septemer of 1965 that dioxin was in the T and that dioxin was highly toxic and he then initiated a program to get the dioxin out of his T. He was interested in the dioxin reduction program because of any prospectie harm that could occur either to the workers or to the public. He thereafter denied concern over consumer problems with regard to the workers, he acknowledged that he never asked anyone at Nitro wherther there were any other problems on the T line other than chlorance. With regard to the customers he never made the determination as to whether or not the product was toxic or non-toxic to humans. He never told the Govt, that the 2,4,5-T he was making had a toxic contaminant. When he got the communication from Dr. Baldeschweiler, he asked Udell and Sharp to give him the analytical method and the chromatograms so they could send them to Baldeschweiler. When he met with Udell -and Sharp he told them to institute process work to reduce dioxin in the product, to determine where and how it was being formed and to remove it from the product if possible to the lowest V. B. 23 to c eu P aj --I co r*l QJ cd X0u (U G Pi H cd OJ O CO C 0 cd rl r-l pco QJ co J-l XJ QJ O cd p i G pO 0 r-! cd X U r-l. p i Cu co ---- - exi--i--1--11--i --1--001--co XQU2J X4J pCOi 1--1 00 d 0 U r--r-1l CaOi XPeeO<Juui0 U CO Pi E ari XJ -- --cu --a.r^ QJ eu Pi P XCO cd d r-l CU QJ P) r*l J-l cd 0 X Pi H CU X J CO x : CO u o H u cd x aECiX G &ex U p i rl a i to O CO O QJ CO P X - P eu co x --1 --1P) r p i p i x : - 0 O co CTv r^ I cd --1p i 0 1 >> U > iX P X cd ex --1d eu 1 E1--1X I X ) P r-l O eu CTv X 0 0 co r - l CU to T--. p eu X 0 <u QJ p i rl eu P X 0 eu c x cd co Pi P) N 0 excd cd eu p i 1 P i 1--1 P cd eu aX cd X C3 X -.Q eu l--l X I- ! co Pi CO X J cd CO co CeOu d 0 0 XJ 0 Pi Pexi cNd cd Peeu)xxO cSd Pi Xeu c(Ud Ur-l CeOu 1 1---- cd 0 r-l X) SQJ eu co d cd eu X X<u cPd T-<PJuXXeu Qcx>S 0 X >vX0 0 X co XO eu XX Ed cd 00 0 l" t X CO co PCeOu--1CX--OPPdTr)vlCXXc&ePeduuXXcPccOddo)J >a i r--OJ1 P0 X H cd 1 m ipi <1- 0 P CM r0-l pi cd Xeu1 0 Pi O PJ CPI XX<PpcECedCdOO)uIi C<XPOPPeBOPrXJu^Iii Xe0PcrG0Xrr-o*u)^il lXp--1crPtcOCePPe--"-dOouinx1lll :XrXXXcd0c0PSr*odl XXPceE0OCc&ndUdx*X"-XPO0PpcCc"rPoO^-Jxl XUePccOe5dduu4cdpPO5C<<oOu5- XXrXX--c(00e&PUdJu01 X1--c0cQe0cBcOerodouI-JxJ1lx1r--XXxc?cece>pdduoui XXXcpccS(ecrUoddou)l mcQCdOJ X I 00 P x> eu P 0 eu M-- i---i i n a- Ni O n H i ncu--- r----i ex>1---1 0 0 r-4O - r-- r-- exm -- r- cm I m r-- v o v o r-- r--i r-- r-- CX - co r^ > v OO r - l i--I O r I r - -- VO O r l l / l r K O r - r-- CX VO I CTV CX CX CX -- O d eu rN cd CTV - 1--I r-- i-- LO O CX CU -CM - CX ON e x e x--- o v --- -- -- -- m o o 00 X cd P & Cu I-- Cr--M 'X>)r-I Hi--11l---i CU-i--i m- om---^.co1 co 00 m-- e--u cm-- in-- I---r--i--I11----IiC<TV1"Oi--OOViCMi --px P co co 00r-l cd eu OJ P - CX-CcMxii---iI n-- r-l-mi Ci--Mi CMi iI----i e--x ri--Pi - i i--e x CM m 1--I CM I--I - I . --l < t O - t -- I COCTV -- I CO i--I r-- CO v o O -- - CO 1-- I-- I--I CO -C O - C O M I O - C O < J - v O r-- I--I f--I r --I XXXXXXcc>0d0Pe5CeaPXodu)uiXX>XXXXcePcPePrrrd--duu-1ll XXXX0eBccdc0PfcPce&r>oJodudo)u)--lv.XXXXXXXUXPeccPScere0r^odduuu-l XHXTXXPX~rCPdedoCdH~-)UJ)U)llC4OIHuUxoP<OoCCOiCXMpr3ModlXliUrCNCrIoroccNii--------r--CeMcCneM--moIiv---u---IIXIxxuHirrrCiCmCiCrmm------CnC--MM----MMiIICiii--XX--iOric0rcicrCN>iO--O--Ci----ncnm---mmMdC--CII0M--Iu-I---I'XU!UICCmrCciCcimcctrvC----IM--OCem---mt--oo--iIUIOUO)xi-i-<<rCOricmrc0os(----CIO----H----mfo-OiX-0IXXfl--l-IrrrrsC--Onmmirr-Cr-----C---eCM---f--llI-O-XI-Ol--XIx-rcX-iCi--cii^mCrimmn--n--C--pM)nm--O--iC1--i--XCui-rCuo-mMivr1rC0----rIH------eC--D--m----Mo-1I0cc-iX1xI-IIuCC-rI..-r-C-l----v-r----^OCe<cM--e---*Mi-O1IOfOlJJ-x-11-I-1--errICe-rVVcCC--------IOC"-ecpe4xM.T----OOx-MiJ'OIvx-x-iC1iI--uIxT"<CrcCvPIov--NiN-rePC--Mmi----"oTIiI--Of-t-x--1uXi -!rCrr0tcmio--C--------N----c--IeMm----OO0Iuo-iIiIix---0rm<C<o-im--Crc1Ci-------CCCMt03}----Moil-v--iXXtIOXICIo-rI>--T1rimicc'o0c-------MI-->--CCt----di-i-l10vIvJ*-X1iIXIi O11COO0IOTcrrvr------O----OC--cC----t--DIM0Vivxui--i-iI'XClrcrIrriVrINm---------IMM-----------------DI1lC---i-iIIIXlrCrcC1Im-<O--------rmCecCt-----M--M-i--CMvfxII-1.X-Mxrim0CCrCIc------rCi----eM-M---M0I-moTcCrCl1-Iixv--roOIX--cnrrcPC0m------Oi----mecO--I0m--PIC--uxIXx-cCP>r--M--meCr-trm----e---O----r}---o-ix--U-xniC<IrmIrmmrm'--vr--i--re-M--P1---fC--l--1IixiXvV--0mPc--cO1--mm--I--iCom--Oo--i01O---1X---IPcNrmiCrCOnt--------im--TM----oC1I----v-1-1IOOI--PXr--ricCNrN-iir--v-d----PO--OmM--i>1>"o-1-u-iI- CO co CO !? co -r-l S (U hJ <u C CO l_3 Cd p P 0 X P00 Xr-l co cd s r ea m CVJ PQ > cHo &<u <u cd assigned during the years 1966-68 by both her superiors and people outside of her division and even outside the Department of Commerce, the find chemical compounds necessary for the production of Agent Orange. Her main problems in this are was in finding tetrachlorobenzene (TCB). Only two domestic producers, Dow and Hooker, existed at the time. Dow did not cross-sell to the industry, Hooker did. This ingredient was needed to produce trichlorophenol (TCP), which in turn, was needed in the production of 2,4,5-T. Other interests wanted TCB as well. Jane Lewis' job was basically to see the military have as much 2,4,5-T as possible. She admits that she was told by some purported Dow employee that Dow had linked chloracne to workers exposed to dioxin in the manufacturing process of 2,4,5-T. However, she said this is all she ever learned of potential health hazards from the defendant companies (all of whom she dealt with). Moreover, she never conveyed this information to anyone in DOD or any other office or branch of the Government. Transcript of deposition: p .7 11 1-19; p .7 11 20-23; p.7 11 24-25; p .8 11 1-11; p.8 11 14-23; p.8 11 24-25; p .9 11 1-2; p.9 11 3-12; p.9 11 13-19; p.9 11 20-25; p. 10 11 I- 4; p .10 11 9-20; p. 10 11 21-25; p.11 11 1-3; p.11 11 4-19; p .11 11 20-25; p. 12 11 1-10; p.12 11 11-20; p. 12 11 21-25; p. 13 11 1-17; p. 13 11 18-25; p. 14 11 1-11; p.14 11 13-21; p .15 11 9-25; p .16 11 1-15; p .17 11 1-7; p .17 11 10-21; p .17 11 20-25; p .18 11 1-15; p.19 11 1-10; p .19 11 11-15; p .20 11 1-10; p.20 11 II- 15; p .21 11 1-25; p .22 11 1-25; p .23 1-3; p .23 11 12-25; p.24 1 1; p .24 11 11-18; p .25 11 8-25; p.26 11 1-25; p .27 11 1-5; p.27 1 16; p.28 1 25; p .29 1 17; p.32 1 15; p.60 11 18-25; p .61 11 1-25; p.62 11 1-25; p .63 11 1-25; p .64 11 1-25; p. 65 11 V. B. 25 ELMER P. WHEELER I- 25; p .66 11 1-25; p.67 11 1-25; p .68 11 1-25; p .69 11 1-9; p.69 11 II- 25; p .70 11 1-20; p.71 11 24-25; p 72 11 1-3; p .72 11 13-25; p.73 11 1-25; p .74 11 1-2; p .75 11 4-25; p .76 11 1-2; p .76 11 10-13; p.76 11 17-25; p .77 11 1-25; p.78 11 1-7; p .79 11 1-25; p .80 11 1-25; p .81 11 1-22; p .81 11 24-25; p.82 11 1-25; p .83 11; p .83 11 9-25; p.84 11 1-5; p .84 11 11-15; p .85 11 1-25; p.86 11 I- 25; p .87 11 1-25; p.88 11 1-13; p .88 11 18-25; p .89 11 1-3; p.89 11 II- 25; p .90 11 1-25; p.91 11 1-25; p .92 11 1-9; p .92 11 17-18; p.93 11 8-15; p .94 11 14-25; p.95 11 1-12; p .96 11 12-25; p.97 11 1-22; p.98 11 14-25; p .99 11 1-4; p.100 11 1-15; p.101 11 6-17; p.101 1 25; p.102 1 19; p.103 11 1-3; p.114 11 14-23; p .115 11 4-12; p .116 11 2-4; p .117 11 6-12; p.118 11 2-4; p .119 11 8-13; p.120 11 17-25; p.21 11 1-25; p .11 11 1-19; p .123 11 1-23; p.124 11 6-14; p .124 11 21-25; p .125 1 5; p .125 11 14-21; p .126 11 6-21; p .127 11 11-17; p.127 11 22-25; p.128 1 1; p.147 11 19-20; p .149 11 2-4; p .152 11 18-25; p .153 11 1-22; p.154 1 17; p.155 11 3-24; p .156 11 13-22; p.157 11 1-24; p .159 11 5-6; p.159 11 1-17; p. 160 11 1-25; p .161 11 1-17; p.165 11 24-25; p .166 11 1-4; p .182 11 12-23; p .183 11 5-7; p .185 11 12-25; p .186 1 5-25; p.187 11 11-25; p.188 11 1-25; p .189 11 1-10; p .189 11 15-25; p.190 11 1-4; p.190 11 19-25; p.191 11 12-25; p.192 1 6; p.1 93 11 19-24; p .194 11 3-11; p.194 11 22-25; p .1 95 11 1-23; p .195 11 7-16. 110 Cool Springs Drive, Camden, South Carolina. Mr. Wheeler is a past employee of Monsanto having been employed almost 28 years from 1947 through 1976 as an Industrial Hygenist. His testimony will include his conclusions with regard to systemic injuries seen in Monsanto workers as a result of dioxin contamination, realization in 1960 that dioxin was 15629 V. B. 26 the causative agent of Nitro and Badishe worker health problems, knowledge of the toxcity of dioxin health experience of Monsanto workers, contacts with representatives from other chemical companies, numerous observations concerning etiology of health hazards. Transcript of March 1, 1984: p.6 11 8-25; p .7 11 12-13; p.7 11 17-25; p .8 1 1; p.9 11 22-25; p.10 11 1-24; p .15 11 17-21; p .23 11 15-22; p .24 11 14-25; p.25 11 1-25; p 26 11 1-25; p .27 11 1-25; p.28 11 1-14; p .29 11 4-25; p .30 11 1-25; p .31 11 1-6; P- 31 11 13-25; p .32 11 1-25; p .33 11 1-25; p .34 11 1-25; p .35 11 1-25; p .36 11 1-25; p.37 11 1-25; p .38 11 1-12; p.38 11 19-25; p .39 11 1-25; p .40 11 1-6; p.40 11 18-25; p .41 11 1-25; p.42 11 1-25; p .43 11 1-25; p .44 11 1-25; p.45 11 7- 25; p.46 11 1-25; p.47 11 1-25; p .48 11 1-15; p .48 11 24-25; p.49 11 1-6; p.49 11 12-25; p.50 11 1-13; p .53 11 21 -25; p .54 11 7-14; p.56 11 13-25; p.57 11 1-25; p.58 11 1-25; p .59 11 1-25; p .60 11 1-14; p .61 11 8- 25; p .62 11 1-25; p.63 11 1-18; p .63 1 25; p .64 11 1-25; p.65 11 I- 25; p .66 11 4-25; p.67 11 1-25; p .68 11 1-25; p .69 11 1-25; p.70 11 II- 25; p .71 11 1-15; p.72 11 1-25; p .73 11 1-25; p .74 11 1-25; p.75 11 1-19; p.75 11 22-25; p.76 11 1-25; p .77 11 1-25; p .78 11 1-25; p.79 11 1-25; p .80 11 1-4; p.80 11 24-25; p .80 11 1-14; p .82 11 11-25; p.83 11 1-10; p .84 11 20-25; p.85 11 1-22; P .86 11 7-25; p.87 1 1; p.88 11 9- 25; p.89 11 1-5; p.89 11 12-25; P *90 11 24-25; p .91 11 1-25; p.92 11 1-25; p .93 11 1-25; p.94 11 1-13; p .94 11 18-25; p .95 11 1-25; p.96 11 1-25; p .97 11 1-25; p.98 11 1-25; p .99 11 1-25; p.100 11 1-25; p .101 11 1-13; p. 101 11 16-25; p.102 11 1-25; p. 103 11 1-25; p.104 11 9-25; p .105 11 1-11; p .105 11 1-11; p.105 11 22-25; p.106 11 1-6; p.106 11 16-21; p g .106 11 23-25; p.107 11 1-7; p .108 11 20-25; p.109 11 1-25; V. B. 27 PAUL F. HOFFMAN, PhD. p- 110 11 1-2; p. 110 11 18- 25; P- 11 1 11 1-25; p.1 12 11 1-8; P- 11 2 11 13-25; P- 114 11 1-8; p.1 16 11 3- 25; P- 117 11 1-25; p .118 11 1- 25; P- 119 11 1-25; p.1 20 11 1-25; P- 121 11 1-25; P* 122 11 1-25; p.123 11 1-25; P- 124 11 1-25; p .125 11 1- 25; p. 126 11 1-25 ; p .127 11 1-25; P- 128 11 1-11 ; P- 129 11 3-25; p.1 30 11 1-25; P- 131 11 3-17; p .131 1 25; P. 132 11 1-25; P- 133 11 1-25 ; p.134 11 1-7; P- 135 11 5-25; p .136 11 1- 25; P- 137 11 1-4; p.137 11 24-25; P* 138 11 1-25; p.139 11 1- 10; p .139 11 21 -25; P- 140 11 1-25; p .141 11 1- 25; P- 142 11 1-25; p.143 11 17-25; P- 144 11 1-25; P- 145 11 1-25; p .146 11 1-25; P- 147 11 1-25; p .148 11 1- 25; P 149 11 1-25; p. 150 11 1-25; p. 151 11 1-24; P- 152 11 8-25; p .153 11 1-25; P- 154 11 2-25; p .155 11 1- 25; P- 156 11 1-25; p.157 11 1-21 ; p. 159 11 1-25; p .160 11 1-25; p .161 11 14- 25; P- 162 11 1-25; p.163 11 1-5; P* 164 11 8- 10; p.1 65 11 1-25; p. 166 11 1-25; P- 167 11 1-25; p. 168 11 1-25; P- 169 11 1-12; p. 171 11 18- 25; P* 172 11 1-25; p.1 73 11 24-25; p. 174 11 1-4; p.175 11 1-25; p.176 11 1-14; P- 176 11 22-25; p .177 11 1- 25; P- 180 11 20i-25 ; p .181 11 1-8; P* 181 11 18-25; P- 183 11 1-25; p .183 11 4- 25; P- 184 11 1-5; p. 184 11 21 -25; P* 185 11 2- 19; p.186 11 21-25; P* 187 11 1-10; p.190 11 21 -25; p.191 11 1-17; P- 192 11 4-25; p .193 11 1-25; P* 194 11 1-25; p.195 1 1 ; p.195 11 24- 25; P- 196 11 1-25; p .197 1 1 ; P- 198 11 1-25; P- 199 11 1-25; p .200 11 1-25; P- 201 11 1-25; p .202 11 1-23; P* 203 11 8- 25; p .204 11 1-9; P- 204 11 13-25; P- 205 11 1-25; p .206 11 1-25; P- 207 11 1-11; p .208 11 8- 25; P* 210 11 11 -25 ; p.211 11 1-25; p. 21 2 11 1-25; P- 213 11 1-22; p. 216 1 25; P- 218 11 1-25; p. 219 11 1-14. 1202 Lake Shore Drive North, Barrington, Illinois. Dr. Hoffman is a past Monsanto employee, was the Product Manager V. B. 28 15631 JOHN S. BUSH, JR. for pesticides group from 1961-1965. Testimony will include facts relevant to marketing and sale of 2,4,5-T herbicides. Transcript of November 22, 1983: p .5 11 12-18; p .9 11 1-6; p.14 1 25; p .15 11 1-9; p .22 11 3-10; p .24 11 21-25; p .26 11 14-25; p.27 11 1-15; p .43 11 19-25; p .44 11 1-4; p.44 11 20-25; p .45 11 1-5; p.48 11 20-25; p .49 11 1-16; p .50 11 11-25; p .51 11 1-2; p .55 11 7-13; p.57 11 6-13; p .60 11 21-25; p .61 11 1-25; p.62 11 1-10; p .63 11 1-10; p. 63 11 20-25; p .64 11 1-22; p .74 11 5-12; p.80 11 24-25; p .81 11 1-6; p.102 11 2-25; p .103 11 1-3; p .104 11 22-25; p.105 I 1; p.107 11 9-13; p .117 11 20-25; p .118 11 1-9; p. 119 11 18-25; p.120 II 1-18; p .130 11 2-11; p .130 1 25; p .131 11 1-25; p .132 11 1-5; p.134 11 3-14; p .139 11 15-25; p.140 11 1-12; p.141 11 14-25; p.142 11 1-6; p.143 11 6-25; p.144 11 1-25; p .145 11 1-25; p .146 11 1-25; p.147 11 1-15; p .147 11 21-25; p.148 1 1; p .149 1 25; p .150 11 1-12; p.150 11 23-25; p.151 1 2; p.151 11 23-25; p .152 11 1-8; p.152 11 20-25; p .153 11 1-11; p .153 11 15-25; p.154 11 1-25; p .155 11 1-25; p .156 11 1-5; p.156 11 9-23; p .157 11 12-25; p.158 11 1-5; p .162 11 5-25; p .163 11 1-25; p.164 11 1-4; p .165 11 11-25; p .166 11 1-25; p .167 11 1-25; p.168 11 1-25; p .169 11 1-9; p.174 11 8-25; p.175 11 1-5; p .175 1 25; p .176 11 1-9; p.187 11 5-25; p.188 11 1-5; p.191 11 11-25; p.192 11 1-25; p.199 11 1-25; p.194 11 1-25; p.195 11 1-25; p.196 11 1-25; p .197 11 1-25; p .205 11 11-25; p.206 11 1-25; p.207 11 1-3; p.207 11 16-25; p .208 11 1-7. 2232 North Military Road, Arlington, Virginia 22207: Mr. Bush is a past Monsanto employee commencing his employment for them in 1962 and terminating in 1972. In 1963, he bacame Manager Government Marketing whose function it was to act as a liason between Monsanto and V. B. 29 1563? William P. Schambra the Government. It was his understanding that Agent Orange was not required to be free from hazardous effects to humans. It was he who was the Monsanto - Government contact. Transcript of February 22, 1983: p .5 II 7-22; p .8 II 9-11; p.9 11 4-19; p.10 11 6-23; p .11 11 1-5; p .11 11 16-25; p .12 11 6-25; p .13 11 1-20; p .14 11 12-25; p .15 11 1-17; p. 16 11 2-7; p .16 11 10-14; p.18 11 20-25; p .19 11 1-8; p.19 11 21-25; p .20 11 1-6; p .20 11 21 -25; p .21 11 1-4; p .21 11 11-25; p.22 11 1-25; p .23 11 1-2; p .24 11 15-19; p.25 11 1-3; p.25 11 6-9; p.25 11 21-25; p .26 11 1-21; p .27 11 13-15; p.27 11 17-18; p.27 11 23-25; p.28 11 1-4; p .29 11 3-25; p.30 11 1-8; p .31 11 3-6; p .31 11 9-15; p.31 11 18-25; p .32 11 1-16; p .33 11 5-25; p.34 11 3-19; p .35 11 21-25; p.36 11 1-25; p .37 11 1-12; p .39 11 7-25; p.40 11 1-25; p .41 11 1-15; p .42 11 18-25; p .43 11 1-6; p .44 11 2-25; p.45 11 1- 25; p .46 11 1-10; p.47 11 11-13; p .49 11 14-22; p.50 11 3-15; p.50 11 24-25; p .51 11 1-17; p.51 11 22-24; p .52 1 1; p .52 11 7-17; p.52 11 19-25; p .53 11 1-3; p.56 11 4-16; p .57 11 10-25; p.58 11 1-25; p.59 11 2-5; p.59 1 8; p.68 11 7-25; p.69 11 1-17; p .71 11 17-25; p.72 11 1-2; p .72 11 5-7; p.72 1 11; p.73 11 17-21. 1411 West Saint Andrews, Midland MI.: Retired Dow employee, with responsibility for negotiating contracts between Dow and others, including the U.S. Government; his testimony relates to his negotiation of contracts for R&D work with Dr. Minarick and Dr. Darrow of the Army Chemical Corp. and that he cannot recall discussing the toxicity of any herbicide at any of the Defoliation conferences that he attended and did not discuss the same with either Dr. Minarick or Dr. Darrow; He also did not discuss health problems encountered by Dow workers with any government V. B. 30 15633 A. E. Sidwell 1984 include ;p.5,ll1-2;p.6,H6-13&18-25;p .7,6-25;p.8,111-8;p.13,ll16-25;p.14, 1 1 1 - 2 5 ;p. 1 5 , 1 1 1 - 2 5 ;p.16,1 1 1 - 2 3 ;p-18, 1111-20&22-25;p.19,111-12&14-16&21 -2 5 ;p.20,111-5&9-17&20-25;p .21,111-25; p . 2 2 , 1 1 1 - 2 5 ; p . 23,111- 7 & 1 3 & 16-19 & 23-2 5 ;p.24,111&5-25;p.25,111-10&12-18&20 - 2 5 ;p.26,111-4,p.28,112-25;p.29,111I3&1 5--25 ;p-30,111-5&17-25;p.31,111-1 4& 16-25;p.32,111-16&20-25;p.33,111 -1 8Sc21 -25; p.34,111 -25; p.35,111 -20Sc24-2 5;p.36,111 --25 ;p.37,H1 --14&1 9-25 ;p.38 ,111-25;p.39,111 -25;p.40,111-25 ;p .41 ,111 -9&1 1-25;p.42,ll1-22Sc24-25;p.43, 11 1 - 9 & 1 3 - 2 5 ;p.44,111- 1 1 4 2 2 - 2 4 ;p.45,1 II -75e9-24 ;p .46,112-6&1 0-1 1&1 4-25 ;p .4 7,111 --2&5 -6&8 --176c25; p.48,111 -4&8&1 019;p.49,1116-1 86c22-25 ;p.50,111 -648-2 2 ;p.52,118-25 ;p.53,111 -2,1 3-25;p.54, 114- 2 5 ; p . 5 5 , 1 1 1 -365-10612 - 2 5 p .56,111 -6,7-19,22-25 ;p.57,111,7-1 5,18-23,25 ;p.58,111-15,19-15;p.59,111-2,4-25;p .60,111 -25;p.61,111-15,19-25 ;p .62,11 1-14,19-25;p.63,111 -1 1 .13-20,22-25;p .64,112-10,13,23-25;p-65,111-13,15-2 3,25;p.66,116-10,12-16,18-25;p.67,11 I- 25;p.68,111 -2,9-1 1,13-22,25 ;p .69,1 II- 5,7-10,12-25 ;p.70,111,3-6,7-12,18 -22,24,25;p.71,111-18,p.72,111-23,25 ;p. 73,111-25;p.74,1,3,16-20,22-25,p . 75.111- 6,14-25;p.76,111-22-24-25;p,7 7.111- 3,7-15,17-25;p.78,111-25,p.79, III-4,6-25;p.80,111-16,22-25 ;p ,81,11 1 -4,7-14,1 7-22,24-25;p.82,111-8,10-1 2,1 4-25;p.83,111 -4,6-1 7,19-22;p,84,1 116-18,20-25 ;p,85,111 -25 ;p ,86,111-25 ; p ,87,1 1 1 , 3 - 2 3 , 2 5 ;p,88,111-10,13-19, 2 1 ;p,89,115-7,9,13-21 ;p ,90,14-16 ;p ,9 4, H15-25;p, 95,1110-10. 1804 West Road, Jacksonville, Arkansas: Director of Chemical Research - Plant Manager, Hercules' Jacksonville plant which produced Hercules' 2,4-D and 2,4,5-TCP & 2,4,5-T; His deposition and attached exhibits will be offered as indicated. He also testified in deposition and at trial concerning the same subjects in Arkansas Department of Pollution Control & ecology, USA & Others vs. Vertac Chemical, Hercules, Inc. & others; V. B. 32 1563 U.S. Dist. Ct., Eastern District of Arkansas, Western Division, Civil #L.R.-C-80-110, and was represented by counsel in both hearings; His testimony relates to his expertise in chemistry, his knowledge of 2,4,5-TCP and 2,4,5-T, and the contaminant TCDD, how and when dioxin is created in the process of manufacture, how its creation can be minimized & how it can be removed (at least in part) by a toluene extraction process: He will also testify to the testing methods available & as used by Hercules and the confidentiality of the entire subject of the presence of dioxin in Agent Orange. He will also testify re "compound X" which they delivered to the government without knowing what it was. Further, he will testify that he participated in preparing and amending the government specification for 2,4,5-T and that the government never rejected a Hercules request for a change in the contract or its specifications; Excerpts from his deposition in this litigation, taken March 6, 1984, will include, P.11 L. 19 - P.12 L. 11; P.17 L.17 - P.18 L.20; P.26 L.3 - P.49 L.9; P.50 L.7 - P.56 L.17; P.59 L.13 - P.69 L. 12; P.71 L.3 - P.102 L.17; P.106 L.9 - P.106 L.22; P.108 L.11 - P.109 - L.6; P.110 L.17 - P.111 L.10; P.112 L.1- P.112 L. 11; P.119 L.24 - P.126 L.15; P.129 L.9 - P.132 L.4; P.132 L.6 - P.132 L. 12; P.136 L.12 - P.136 L.16; P.138 L. 16 - P.141 L.3; P.147 L.2 - P.148 L.2 (ex 3); P.148 L.4 - P.148 L.20 (ex 4); P.158 L.4 - P.162 L.21 (ex 5); P.162 L.22 - P.166 L.21 (ex 6); P.166 L.22 - P.169 L.16 (ex 7); P.169 L. 18 - P. 174 L.7 (ex 8); P.174 L.8 - P.177 L.19 (ex 9); P.178 L.2 - P.179 L.10 (ex 10); P.179 L.12 - P.186 L.10 (ex 11) ; P.186 L.15 - P.191 L.10 (ex 12) ; P.191 L.11 - P.194 L.25 (ex 13) ; P.195 L.1 - P.195 L.23 (ex 14); P.201 L.6 - P.206 L.1 (ex 15); P.206 L . 18 - P.217 L.6 (ex 16); P.217 L.7 - P.227 L.21). V. B. 33 15635 PETER G. ARVAN 4475 Laguna Place, Boulder,Colorado; Mr. Arvan is a past employee of Monsanto having worked for them from 1949 through 1978. In 1960, he became Director of Product Sales in the Agricultural Chemical Division and was Assistant General Manager of that division from 1964 - 1968. It was Mr. Arvan's suggestion that a substantial amount of Agent Orange that Monsanto sold to the Government had previously been purchased by Monsanto from the Government. It should be noted that a second deposition of Mr. Arvan was recently held - that transcript is not yet available. Transcript of November 28, 1983: P.5 L. 14-25; P.6 L. 1-2; P.6 L.10-25; P.7 L. 1-5; P.14 L. 1-14; P.31 L.13-25; P.32 L. 1-25; P.33 L. 1-25; P.35 L. 1-25; P.36 L. 1-25; P.37 L. 1-21; P.39 L. 14-23; P.40 L. 9-25; P.41 L. 1-2; P.41 L. 12-25; P.42 L.1-25; P.43 L. 1-5; P.43 L. 22- 25; P.44 L.1-3; P.45 L. 7-25; P.46 L. 1-25; P.47 L. 1-6; P.47 L. 23- 25; P.48 L. 1-11; P.48 L. 25; P.49 L. 1-8; P.49 L.22-25; P.50 L. 1-4; P.52 L. 1-25; P.53 L. 1-10; P.56 L. 17-25; P.57 L. 1-6; P.60 L. 1-5; P.61 L. 7-13; P.65 L. 15-25; P.66 L. 1-9; P.66 L. 21-25; P.67 L. I- 25; P.68 L. 4-6; P.69 L. 3-6; P.70 L. 4-11; P.71 L. 6-19; P.72 L. 3-18; P.73 L. 2-13; P.75 L. 16-25; P.76 L. 1; P.78 L. 24-25; P.79 L. 1-6; P.81 L. 16-25; P.82 L. 1-3; P.87 L. II- 25; P.88 L. 22-24; P.91 L. 23-25; P.92 L. 9-12; P.92 L. 17-18; P.94 L. 12-25; P.95 L. 1; P.97 L. 25; P.98 L. 1-2; P.102 L. 8-19; P.123 L. 17-25; P.127 L. 25; P.128 L. 1-6; P.129 L. 19-25; P.130 L. 1-8; P.132 L. 18-25; P.133 L. 1-25; P.134 L. 1; P.134 L. 9-14; P.135 L. 17-25; P.136 L. 1-4; P.155 L. 1-25; P.156 L. 1-11; P.157 L. 1-11; P.158 L. 1-10; P.158 L. 18-25; P.159 L. 1-24; P.160 L. 5-15; P.165 L. 7-25; P.166 L. 1-17; P.172 L. 17-25; P.173 L. 1-25; P.174 L. 1-25; P.175 L. 1-7; P.181 V. B. 34 15636 L. 3-13; P .182 L. 21-25; P. 183 L. tr< 0 1 1-25; P. 184 25; P.,185 L. 1-25; P.,187 L. 17 -25; P .188 L. 1-3; P. 189 L. 6-25; P .190 L. 1-25; P. 191 L. 1-25; P.193 L. 3- 25; P.,194 L. 1-25; P..195 L. 1-25; P. 196 L.. 1-25; P. 197 L., 1-25; P. 198 L- 25; P..199 L. 1-25; P..200 L. 1-25; P. 201 L., 1-25; P. 202 L. 1-25; P .203 L. 16-25; P. 204 L. 1-2; P. 205 L. 1-25 ; I>.206 L . 1-6; P. 207 L. 1- 25; P. 208 L., 1- 20; P. 214 L. 14-25; P.215 L. 15-25; P. 218 L. 3-6; P.218 L. 21- 25; P.,219 L. 1-25; P..220 L. 1-9; P. 235 L., 1-25; P. 236 L., 1-7; P. 236 L. 19 -25 ; I>.237 L . 1-6; P.,242 L. 1-25; P. 243 L., 1-25; P. 250 L. 12 -25; P. 251 L. 1-4. V. B. 35 15637 HERBERT YORK JEROME B. WIESNER 6110 CAMINO DE LA COSTA, LA JOLLA, CA. Deposed August 3, 1983. He was a physicist and chief scientist of ARPA and was the first director of defense research and engineering. Was a member of PSAC 1957-58, 1964-65. PSAC Vice Chairman from February 1965-67. Does not recall the PSAC briefing on defoliants discussing potential toxicity to humans. Only remembers defoliation discussed with reference to reducing ambushes. No recollection of mention of contaminant in Agent Orange during PSAC tenure and unaware of any health hazards associated with defoliants. P 6, L 17-25; p pp. 7-10, all; p 16, L 20-25; p 17, all; p 21, L 12-25; p 22, all; pp 23-24, all; p 25, L 3; p 29, L 18-24; p 30, L 20-25; p 31, L 1-8; p 34, L 8-25; p 36, L 6-25; p 37, L 1-16; p 40, L 9-25; p 41, all; p 42, all; p 43, all; p 45, L 17-25; p 47, L 3-17; p 48, L 9-15; p 49, L 1-18; p 55, L 5-16, 22-25; p 56, all; p 57, all; p 58, all; p 59, all; p 60, L 1-16; p 61, L 5-8; 63, L 12-25; p 64, L 1-22; p 65, L 15-25; p 67, L 23-4; p 68, L 1-2, 24-25; p 69, all; p 70, L 1-11; p 81, L 9-17; p 132, L 8-24; p 134, L 1-25; p 135, L 1-25; p 136, all; p 137, all; p 138, all; p 139, L 1-15. 61 SHATTUCK RD, WATERTOWN, MA. PSAC Memember (1958-1967); Chairman (1 961 -1 964); and Member of NSC (1961-1964). Never discussed dioxin in the context of a meeting. No presentations on chloracne or use of herbicides in Southeast Asia. p. 6, L 10 to p . 15, L 20 ; p . 16, L 1 to p. 28, L 10 ; p . 30, L 4 to p. 31 L 5; p. 31, L 17 to p. 32, L 20; P- 33, L 1 to p. 35, L 12; p. 35, L 23 to p. 36, L 1 ; P . 36, L 6 t o p . 36 L 6 ; p . 36 , L 12 to p . 38,NL 9 ; 15638 V. B. 36 FRANK H. WESTHEIMER James 0. King p- 38, L 15 to P- 39, L 15; P- 39, L 24 to P- 39, L 25; P- 40, L 11 to P- 40, L 15; P- 41 , L 4 to p. 45, L 23; P- 46, L 16 to P- 46, L 19; P- 47, L 1 to P- 47, L 17; P- 47, L 22 to P48, L 7; P- 48, L 14 to p . 48, L 15; P- 49 , L, 10 to P* 50 , L 1 ; P- 50, L 11 to P . 63, L 3 ; p . 65, L 7 to P- 65, L 12 ; p . 69, L 9 to p . 70 , L 3; P- 70, L 21 to P- 70, L 25; P- 71 , L 17 to P- 72 , L 23 ; P 75, L 9 to P76, L 4; P- 76, L 17 to p. 78, L 12; P- 78, L 21 to P* 81 , L 21 ; P- 82, L 1 to P- 85 , L 2; P- 85, L, 17 to P91 , L 9; P- 91 , L, 18 to p. 93 , L 9; P- 93 , I. 25 toi p. 94 , L 4; P- 94, L 2 .15 to P- 94 , I, 21 ; p . 95, L 6 to P- 95, L 13; P- 95, L 22 to P- 109, L 3 BERKELEY STREET, CAMBRIDGE, MASS. On Ground Warfare, Educational & Research Development and Chemical and Biological Warfare Panels of PSAC. Discussed herbicides in CW context, but did not discuss health problems associated with them. P6,L6 to p20, L5;p20,L12 to p24,L6; p24, L17 to p 4 1 , LI 4; p 4 1 , L23 to p 4 5 , L 3 ; p52, L14 to p57, LI; p57,L18 to p61,L7; p61,L22 to p67, L2 0 ; p69,L6 to p72,L2; p72,L9 to p72,L22; p73,L5 to p74,L4; p75,L8 to p82,L10; p82,L23 to p85,L23; p87,L8 to p 91 ,L5 ; p92 ,L1 3 to p92,L24; p93,L10 to p94,L16; p96,L9 to p96,L23; p99,L7 to p 99,L18; P.0. Box 900 Alpharetta, Georgia; Former employee Diamond Shamrock; excerpts from transcript of deposition; p. 8, LL 7, 12 & 16; p. 9, LL 17 & 22; p. 11 L 20; p. 12, L 5; p. 22, LL 7 & 11; p. 24, LL 7 & 17; p. 26, L 13; p. 27, LL 4 & 15; p. 28, L 16; p. 29, LL 3, 7, 16 & 19; p. 30, L 17; p. 31, L 5; p. 34, L 25; p. 35, LL 7 & 8; p. 36, LL 3 & 10; p. 37, LL 19 & 25; p. 40, L 2; p. 42, LL10 & 18; p. 43, LL 9, 20 & 23; p. 44, L 10; p. 45, LL 15, 18 & 22; p. 48, 12, 17, 18 St 21 ; p. 50, L 17; p. 51, L 11 ; p. 52, L 20; V. B. 37 George C. Kempson p. 53, LL 1, 10 & 25; p. 57, LL 6, 10, 16, 18, 23 & 25; p. 58, LL 13 & 16; p. 59, L 15; p. 60, L 23; p. 66, L 11; p. 69, L 22; p. 70, LL 16 & 25; p. 71, L 25; p. 73, L 17; p. 79, LL 6 & 19; p. 81, LL 10 & 24; p. 84 LL 1 & 9; p. 85, L 22; p. 86, L 15; p. 87, LL 1 & 22; p. 88, LL 1 & 7; p. 94, LL 3 & 23; p. 95, LL 3 & 8; p. 98, LL 2 & 7; p. 104, LL 11 & 19; p. 109, L 12; p. 110, LL 1 & 25; p. 111, L 12; p. 112, LL 11 & 22; p. 114, L 19; p. 115, LL 1, 10 & 16; p. 117, L 23; p. 118, LL 1, 12, 15, 21, 23 & 24; p. 119, L 3; p. 122, LL 19 & 24; p. 123, LL 2 & 7; p. 124, L 25; p. 125, LL 5 & 25; p. 126, L 19; p. 127, LL 1 & 19; p. 129, LL 4 & 14; p. 130, L 25; p. 132, L 8; p. 145, LL 9 & 24; p. 147, LL 4, 9 & 19; p. 148, L 6; p. 152, LL 10 & 18; p. 156, L 25; p. 157, L 8; p. 162, L 23; p. 164, L 16; p. 168, L 23; p. 170, LL 7, 16 & 22; p. 172, L 23; p. 173, L 23; p. 180, L 9; p. 195, L 2; p. 196, LL 4 & 17; p. 198, LL 10 & 20; p. 203, LL 9 & 15; p. 208, L 16; p. 214, L14; p. 215, L 24. 143 South Gore, Webster Groves, Missouri. George Kempson is a past employee of Monsanto and was employed by Monsanto from 1955 - 1975. From 1960 - 1964, he was a District Manager of the Agricultural Division and from 1964 through 1968, he was the Director of Marketing. He receives a pension from Monsanto of approximately $11,000 $ 1 2 ,000/year. Never told anyone outside of Monsanto that the product that they were selling was contaminated with dioxin. Never did any research or requested any research while at Monsanto about dioxin. Members of the marketing department who had monthly meetings about 1963 or 1964 included the general manager, the assistant general manager and directors of marketing, manufacturing, research, administration, development and personnel. He attended those V. B. 38 15640 meetings when he became Director of Marketing. Never was apprised of any worker health problem in the 2,4,5-T manufacturing plant and claims to have heard the word chloracne for the first time several years ago. Not aware of does not recall that the 2,4,5-T workers refused to work in that plant and were given bonus pay in order to induce them to work. Spoke to Dr. Emmet Kelly quite often, but Kelly never advised him that 2,4,5-T workers had problems nor did Kelly advise him that the 2,4,5-T ws contaminated with dioxin. The monthly committee meetings above referred were called the number one committee meeting. If before 1965 he knew that T was contaminated with a chloracnegen, had marketing been informed it would have come from research. Claims that research would have stopped it there and if it effected human beings or animals or so forth, that would have been discussed with medical and if proven, they would have stopped it. Assuming that a great deal of the product had already gone out to the market with the contaminant, he is prositive that they (marketing) would have been asked to recall the product promptly. He was involved in contract negotiations between Government and Monsanto with regard to Monsanto supplying D and T. He approved the Government purchasing orders when they came in. Doesn't remember if Monsanto had a contract. He did not deal directly with the Government - it was Redd Zorsch. Zorsch and Hoffman knew the specifications of T and D. He was Zorsch's superior and Zorsch kept him apprised of the negotiations between Government and Monsanto regarding purchases of herbicides. Claims that he knew of no other company that was producing 2,4,5-T. Acknowledges that there is a possibility Russell could have suggested to the Government what the specifications should be in V. B. 39 V Missouri. George Kempson is a past employee of Monsanto and was employed by Monsanto from 1955 - 1975. From 1960 - 1964, he was a District Manager of the Agricultural Division and from 1964 through 1968, he was the Director of Marketing. He receives a pension from Monsanto of approximately $11,000 $12,000/year. Never told anyone outside of Monsanto that the product that they were selling was contaminated with dioxin. Never did any research or requested any research while at Monsanto about dioxin. Membersof the marketing department who had monthly meetings about 1963 or 1964 included the general manager, the assistant general manager and directors of marketing, manufacturing, research, administration, development and personnel. He attended those meetings when he became Director of Marketing. Never was apprised of any worker health problem in the 2,4,5-T manufacturing plant and claims to have heard the word chloracne for the first time several years ago. Not aware of does not recall that the 2,4,5-T workers refused to work in that plant and were given bonus pay in order to induce them to work. Spoke to Dr. Emmet Kelly quite often, but Kelly never advised him that 2,4,5-T workers had problems nor did Kelly advise him that the 2,4,5-T ws contaminated with dioxin. The monthly committee meetings above referred were called the number one committee meeting. If before 1965 he knew that T was contaminated with a chloracnegen, had marketing been informed it would have come from research. Claims that research would have stopped it there and if it effected human beings or animals or so forth, that would have been discussed with medical and if proven, they would have stopped it. Assuming that a great deal of the product had already gone out to the 1564? V. B. 41 market with the contaminant, he is prositive that they (marketing) would have been asked to recall the product promptly. He was involved in contract negotiations between Government and Monsanto with regard to Monsanto supplying D and T. He approved the Government purchasing orders when they came in. Doesn't remember if Monsanto had a contract. He did not deal directly with the Government - it was Redd Zorsch. Zorsch and Hoffman knew the specifications of T and D. He was Zorsch's superior and Zorsch kept him apprised of the negotiations between Government and Monsanto regarding purchases of herbicides. Claims that he knew of no other company that was producing 2,4,5-T. Acknowledges that there is a possibility Russell could have suggested to the Government what the specifications should be in producing Orange and says perhaps he did see documents which indicated that. Russell was "possibly" involved in writing the specifications. Acknowledges that Russell "perhaps he could have" indicated to him that Russell was so involved. Does not remember when he approved the specifications whether he compared the Government specifications and the Monsanto specifications. Doesn't recall whether the specifications call for production of dioxin. If he knew that following specifications would have produced an acutely toxic by-product, the production would not have been approved. Transcript of January 20, 1984: p.49 L. 6-25; p.46 L. 1-8; p.52 L. 22-25; p .53 L. 1-16; p.54 L. 7-20; p .57 L. 3-25; p .58 L. 1-15; p.59 L. 12-25; p .60 L. 1-25; p .61 L. 1-2; p .61 L. 21-25; p.62 L. 1-5; p.63 L. 12-25; p .64 L. 1-25; p.65 L. 1-25; p.66 L. 1-23; p.67 L. 6-25; p.68 L. 1-25; p .69 L. 1-25; p.70 L. 1-24; p .72 L. 13-25; p .73 L. 1-25; p.74 L. 1-25; p .75 L. 1-25; p.76 L. 1-25; p .77 L. 21-25; p.78 L. 1-25; p.79 L. 1564 q V. B. 42 Donald K. Ballman* Eugene D. Crittenden, Jr. J. K. Leasure 1-4; p .81 L. 15-25; p . 82 L. 2-25; p .83 L. 1-25; p.84 L 1-24; p .86 L. 1-25; p .87 L. 1-25; p . 88 L. 1-25; p .99 L. 9-18; p.101 L. 2-22; p . 103 L. 19-25; p.104 L. 1-25; p .105 L. 1- 8 . 722 Revelle Drive, La Jolla, California; Former Vice-President, Marketing Division, Dow Chemical during the mid-60's, and claims no relcollection of any relevant matters. In fact, he disclaims any specific knowledge of and/or responsibility for Dow's government sales, despite being copies on numerous relevant exhibits; Deposition taken November 1, 1983; p.6,1118-25;p.7,111-3;p .12,115-25;p . 13,111-20;p . 14-114-8;p.15,116-22;p.1 6,1112-18;p.17,1113-25;p.18,1112-22; p.19,1112--18;p.21,112-4&24-25;p .22,1 11-25. 908 Dupon Road, Wilmington, Delaware, 19807, was deposed February 10, 1984; Vice-President of International Division of Hercules; Substance of testimony; Director of Sales in Synthetics for Hercules, May, 1966 until October, 1967 and then Assistant General Manager, synthetics, until July, 1968. He never heard of the contaminant dioxin until the Seveso accident in 1976. Excerpts include, p .5,LL6-p.8,LL21; p .16,LL16-p.17,LL16 ;p .17,LL25-p.19,L L14;p,19.LL15--p .21,LL14. Rural route No. 2, Box 157, Makanda, Illinois; Former employee of Dow, was a researcher in the application of herbicides and the development thereof from approx. 1955-1966 at Dow; Research group leader involved in screening and early testing of chemical materials to find out if they had any apparent utility as herbicides; in about 1964, became "responsible for government contract 0-v "a." V. B. 43 Albert E. Hayward 22-24;p . 56, LL 1-13 & 15-25; p. 57 LL 1-8, 18-23 & 25; p. 58, L L 1 , & 12- 13 & 17-25; p. 59, LL 1; p. 60, LL 13-25; p. 64, LL18-20 & 24-25; p. 65, LL 1-10; p. 67, LL23-25; p. 66, LL 1-7 ;12-20;p .69, LL 15-25; p. 70, LL1-5 & 12-18; 5716 Jefferson Blvd., Braddock Heights, Maryland 21714; he was Director of the Program coordination office at the U.S. Army Biological Laboratories at Fort Detrick; he will testify that at the first "Defoliation Conference" with the defendants in 1963 at the U.S. Army Biological Laboratories it was understood by all that the defoliation program in Southeast Asia would not be developed in the usual military industrial collaboration but rather reliance on the experience and knowledge of the various commercial producers would be significant; and he will further testify that he first heard that Agent Orange might be contaminated with Dioxin in 1969; p. 8, LL 10-11 & 12-14; p. 9, LL 7-10 & 23-25; p. 10, LL 1-3 & 11-14; p. 11, LL 14-19; p. 12, LL 1-3, 12-16 & 17-23; p. 13, LL 6-11 & 19-25; p. 14, LL 1-4, 9-12, 13-16, 17-19, & 20-22; p. 15, LL 3-6, 14-21; p. 16, LL 2-6, 10-12, 13- 15, 16-22, 23-24 & 25; p. 17, LL I- 2 & 21-25; p. 18, LL 1-2, 10-12 & 19-23; p. 19, LL 3-6, 7-11, 19-21 & 24-25; p. 20, LL 4-8, 9-10 & 16-17; p. 21, LL 1-6; p. 23, LL 12-14; p. 24, LL 7-8, 9-12, 13-15 & 24-25; p. 25, LL 1, 14-17 & 23-25; p. 26, LL 2, 3-5, 6-9 & 10-16; p. 27, LL II- 12, 13-14, 15-19 & 20-25; p. 28, LL 1-5, 9-15 & 18-25; p. 29, LL 1-3, 4-7, 11-17 & 18-25; p. 30, LL 1-3 & 13-20; p. 31, LL 1-5 & 13-15; p. 32, LL 1-5; p. 34, LL 21-25; p. 35, LL 1-2 & 16-23; p. 36, LL 8-13, 14-18 & 19-23; p. 37, LL 5-7, 13-14, 15-18 & 19- 21; p. 38, LL3-4, 15-19 & 20-22; p. 39, LL 4-10; p. 40, LL 10-17 & 18-21; p. 41, LL 4-7, 8-12, 13-15 & 20-25; p. 42, LL 1-3, 9-16, 17-21 & 25; p. 43, LL 1, 2-3, 4-10, 14-17, V. B. 45 1504? 6&P&&2PP&L22P&2222522855912221111111111111111111111111c11-111033925792L-596-2--333-4--041-6228--961-8-71732-24-3---9-----3--------------1-----1-11--122222112222122122121121121212222,,0,,3,,3123211111132893036358677583552575594514,7,5--2558711;22;;;;;;;;;;;;-;;,;36901---2;;;222252L66,&64,,06&&6L6511-1ccccc1545;;1L6&3,6p4p6-3pL66&--ccccc1;6ppPPPPPLPpPPPP22P2.P22P161---21..;9911---81-*1,-pL-.P------.L3004L.42L22072176-p9L,.30L4L24-2----26--7--7114&p85pp624772280522-4121-1---117.c11262522.435-,,46455.96999.5-88788812116811-1-11-cc12221,5;62592;;;69879;;2;,2,12025-202010914,;c15955;,,,;,1,,L,;;4,,,,5,18-31-111-1212;1;,;L,p,p;Lp,&,ppL6pLppL07-771-8-c512822L1L85.Lp.6LpL6pp2....LLL..L--cc54L5,LLLLLLLL2-LLLLLL2221...9,.2P;L;L;LLP6LLLLLLp6264-35L5P62788894016771ccc06115-3-670089LL;;.--L-94--2568-1-71, 1LppL0-Lp2656-62-251181-41111,,;;,,,,,,,482785Lp,,,..2p,,,.6,336062-11--111--2,125;p4,44p3,LL,.LLL.-LL-462L-11--1--12--;172211428025L74,;L-.LL.,LLLLL57LL2L480-1-10--1162,,58951;51,;;;;LL8LL7,9p4497-7021-01;1;;;5;6;p,,554p647,7-7--296136--1114-.c2141172,&1pp,854,p,.,,2.-2----11------3161145,622p49L,173,pp1,pppL.Lp.L.-L8-2---96,L3;0,733,,L,6L,,,.,,.,.LL...3L67LL7L13. ,8,LL,,6,LL,6,,,LL-111-11111c1LL2p7873999668787172-760111017111111, 22----5--26.64503311L6-13856--49-1521-1111126114120211111102112;--,,L;,,,,-,,374-.,,141-----71--1-------11111111622800024111112111-111-9-------1121812145923825264p43LLL42LLLLLLLLp110662;4,;;,6,,L,,6.,LLL,LLL666,,,,6LLLL&666&666,66.6,;,cccccccccccccc 15646 V. B. 46 RAYMOND A. GUIDI Francis Kennedy 14-25; p. 115, LL 1-2 & 3-11; p. 117, LL 11-15 & 16-25; p. 118, LL I- 5, 15-19 & 16-25; p. 119, LL 1-4, II- 16 & 19-25; p. 120, LL 18-21; p. 121, LL 15-17; p. 123, LL 1-10 & 21-24; p. 124, LL 1 & 2-12; p. 125, LL 5-12, 13-19 & 20-25; p. 126, LL 1-7, 11-16 & 23-25; p. 127, LL 1-7, 8-15, 16-20 7 21-23; p. 128, LL 3-6, 8-11 & 12-16; p. 129, LL 8-10, 11-14 & 15-16; p. 130, LL 9-12 & 14-17. 420 Essex Place, Memphis, TN.: Former assistant Diamand Shamrock plant manager who will testify concerning health problems in Diamond Shamrock's plant, and knowledge of toxicity of end product and process details relating to that company. p- 14 LL 20-25; p 15 LL 1-7; P- 15 LL 8- 15; P- 15 LL 22- 25; P- 16 LL 1-:3; p .16 LL 4-25; P- 17 LL 14-:25; p- 18 LL 1-9; P- 19 LL 12- 18; P- 19 LL 22 -25; P. 20 LL 1- 11 ; P- 21 LL 9- 16; p. 22 LL 24 -25; p . 23 LL 1-4; P 49 LL 7- 25; P- 24 LL 10- 25; P- 25 LL 1 ; p. 22 LL 2-1 7; P- 23 LL 14-:20; P- 26 LL 9-24 ; p- 27 LL, 2- 15; P- 28 LL 1-16;, P* 30 LL 14- 20; P- 30 LL 21 -25; P* 31 LL 1 ; P- 32 LL 10- 25; P- 36 LL 1-1 5; P 39 LL 2-7; P- 39 LL 20 -25; p. 40 LL 1- 14; P- 40 LL 16 -21 ; P- 44 LL 3-14 9 P. 44 LL 14 -25; P- 45 LL 1-6; pi. 41 LL 4 -14 P- 45 LL 11 -14; P- 43 LL 19- 23; P- 38 LL 10-14 P- 40 LL 16- 21 ; P- 45 LL 15 -25; P 46 LL 1-14; P- 46 LL 14 -22; P- 46 LL 23 -25; P- 47 LL 1 ; p. 47 LL 2-6. Address not shown on transcript; Mr. Kennedy started with Diamond in 1953 and became plant manager in Newark in 1963. He was first familiar with serious health hazards in Newark Plant in 1954 and until 1968 when transferred to Cleveland. Will testify as to purpose of Midland meeting, Dow's dioxin detection procedures, relation between dioxin content and health hazards, and dioxin levels of Diamond's product. V. B. 47 Eugene A. Outright p. 26 LL 1-2; p. 27 LL 23-25; p. 48 LL 12-19; p. 44 LL 14-25; p. 45 LL 1-10; p. 48 LL 16-24; p. 50 LL 3-8; p. 53 LL 3-25; p. 54 LL 1-1; p. 55 LL 23-25; p . 56 LL 1-3; p . 57 LL 25; p. 58 LL 1-9; p. 61 LL 15-18; p. 53 LL 3-25; p.54 LL 1-19; p. 71 LL 1-20; p. 105 LL 1-4 and LL 18-23; p. 113 LL 3-8; p. 115 LL 3-19; p. 115 LL 3-19; p. 116 LL 23-25; p. 117 LL 1-12; p. 127 LL 14-25; p. 128 LL 7-25; p. 129 LL 1-6; p. 129 LL 7-20; p. 132 LL 7-12; p. 132 LL 6-25; p. 135 LL 14-17; p. 135 LL-14; p. 206 LL 20-25; p. 207 LL 1-22; p. 207 LL 19-22; p. 138 LL 24-25; p. 139 LL I-18, P 139 1 14-25, P140 1 1-2, p. 142 LL 1-25; p. 143 LL 1-3; p. 143 LL 19-25; p. 145 LL 9-21; p. 70 LL 4-11; p. 71 LL 1-11; p. 66 LL 19-25; p. 67 LL 1-6; p. 67 LL 7-14; p. 124 LL 22-25; p. 123 LL 1-9; p. 45 LL II- 18; p. 98 LL 6-20; p. 209 LL 1-5; p. 149 LL 2-20; p. 152 LL 18-25; p. 153 LL 1-3; P . 156 LL 7- 21 ; p- 104 P.LL 11- 16; 103 LL 15- 25; p. 104 P*LL 1-10; p. 104 LL 7-25; 105 LL P-1-23; P* 109 LL 19-25; 110 LL 1-16; p . 77 LL 9-21 ; p. 77 LL 22- 25; P*p . 166 LL 17- 25; p . 167 LL 1-4; P- P-177 LL 24 -25; 178 LL 1- 25; P- P-179 LL 1-12; 179 LL 14- 16; P-183 LL 8-1 6 ; p. 180 LL 14- 20; 182 P-LL 12-16; p . 182 LL 17-22; 181 LL P- P-10-19; 185 LL 3-14; 185 LL P* P*15-17; 184 LL 16-19; 188 LL P P-14-25; . 189 LL 1-5; 129 LL P- P-12-15; 193 LL 4-2; 194 LL P* P.1-25; 193 LL 12-14; 198 LL 3-5, p. 202 LL 7; p. 203 LL 5- 25; p. 206 LL 1; P. 204 LL 2-3; P- 202 LL 12-14; P . 204 LL 4-10 ; p. 19 LL 2-25; p. 220 LL 1-4; p. 218 LL 21-25; P. 211 LL 1- 10; p. 219 LL 1 ; p. 220 LL 22-25 ; p. 211 LL 1-10; P- 221 LL 9-11. 1474 Maplewood Drive, Macon, Georgia. Deposition taken January 18, 1984. He is a past employee of Monsanto, having been employed by them from 1957 to 1969. His involvement with 2,4,5-T occurred from 1966 to 1969 when he was the V. B. 48 John W. Tukey Production Supervisor at Nitro. He is a chemical engineer and testified concerning 2,4,5-T process and analysis. Analytical tests for dioxin was not done on a regular basis but only for "special cases" - research efforts. Attempted to set tentative permissable dioxin levels at 10ppm. Was aware of process and equipment malfunctions. P 6, L 5-9, 19-25; p 7, L 1-8; p 9, L 7-8, 13-20, 25; p 10, L 1-6, 9-11, 22-25; p 11 , L 1,2, 7-25; p 12, L 1, 6-10; p 44, L 14-16; p 46, L 12-25; p 47, L 1-4, 16-25; p 49, all; p 50 L 1-6; p 52, L 3-25; p 53 all; p 54, L 1-7; p 55, L 5-7, 19-25; p 56, L 1-13; p 57 all; p 58, L 1-10, 20-25; p 59 all; p 60, L 1-21; p 61, L 3-25; p62 L 3-8, 13-18, 25; p 63 all; p 64 all; p 65, L 1-5, 11-22; p 66 all; p 67 all; p 69 all; p 70, L 1-5, 21-25; p 71, L 1-14, 20-25; p 72, L 1-9; p 73 L 16-24; pp. 74-75 all; p 76, L 1-8, 20-25; p 77, L 5-25; p 78 all; p 79 L 1-23; p 80, L 6-7; p 81 all; p 82, L 1-9; p 84, L 13-25; p 85, L 1-15; P 88, 6-10; p 89, L 6- 25; pp. 90-94 all; p 95, L 1; p 96, L 21-25; p 97, L 1-17; p 98, L 12-25; p 100, L 8-25; p 101, L 1-2; p 104, L 4-25; p 105, L 10-14; p 106, L 5-25; p 107, L 1-11; p 109 all; p 110, L 1-18; p 111, L 7-24; p 112, L 9-25; p 113-114 all; p 115, L 1-12; p 118, L 3-16; p 119, L 10-21 ; p 120, L 20-25; p 121, L 1-8, 22-25; p 122, L 1-9; p 124, L 1-6, 18-24; p 126, L 15-18; p 127, L 9-13, 22-25; p 128 all; p 129, L 18-22; p 131, L 7- 25; p 132, L 1-23; p 133, L 13-25; p 134, L 1-3; p 135, L 6-25; pp. 136-139 all; 140, L 13-25; 141, L 1-8; p 143, L 8-16; p 144, L 17-25; p 145, L 3-15; p 146, L 11-25; p 147, L 1-5; p 148, L 12-25; p 149, L 1-16; p 150, L 9-11, 14-15, 22-25; p 151, L 2-8, 24-25; p 152, L 1-14; p 157, L 19-25; p 158, L 1-11, 19-25; p 159, L 1-15; p 161, L 9-22; p 162, L 1-5. 115 Arreton R d , Princeton, New 15849 V. B. 49 Herbert York Jersey. Deposition taken October 3, 1983. Member of President's Science Advisory Committee from 1960-1963. First heard term dioxin in 1969. Had no recollection of any specific herbicides being employed in Vietnam. Member Herbicide Panel. P 7, L 21-25; p 8, L 1-25; p 9, L 4-25; p 10, L 1-25; p 11, L 1-5; p 13, L 14-25; p 14, L 14-25; p 15, L 1-15; p 23, L 3-25; p 24, all; p 25, L, all; p 26, L 10-25; p 27, L 1-20; p 28, L 3-25; p 29, L 1-3; p 30, L 8-13, 24-25; p 31, L 1-25; p 32, L 1-3, 1.0-25; p 33, L 3-21 ; p 34, L 3- 25; p 35, L 1-5, 16-24; p 36, L 4- 6, 16; p 48, L 8-25; p 49, 1-2; p 54, 10-25; p 55 all; p 56, L 1-8, 18-25; p 57, L 1-25; p 58, all; p 59, L 1-12, 17-18, 25; p 60, all; p 61, all; p 62, all; p 63, L 1-8; p 64, L 4-25; p 65, L 1-17, 22-25; p 66, L 1-20; p 67, L 13-25; p 68, L 1-20; p 70, L 20-24; p 72, L 7- 25; p 73, all; p 74, L 1-13; p 75, L 10-13; p 78, all; p 79, L 1-9; p 81, L 1-19. 6110 Camino De La Costa, La Jolla, CA. Deposed August 3, 1983. He was a physicist and chief scientist of ARPA and was the first director of defense research and engineering. Was a member of PSAC 1957-58, 1964-65. PSAC Vice Chairman from February 1965-67. Does not recall the PSAC briefing on defoliants discussing potential toxicity to humans. Only remembers defoliation discussed with reference to reducing ambushes. No recollection of mention of contaminant in Agent Orange during PSAC tenure and unaware of any health hazards associated with defoliants. P 6, L 17-25; p pp. 7-10, all; p 16, L 20-25; p 17, all; p 21, L 12-25; p 22, all; pp 23-24, all; p 25, L 3; p 29, L 18-24; p 30, L 20-25; p 31 , L 1-8; p 34, L 8-25; p 36, L 6-25; p 37, L 1-16; p 40, L 9-25; p 41, all; p 42, all; p 43, all; p 45, L 17-25; p 47, L 3-17; p 48, L 9-15; p 49, L 1-18; p 55, L 5 - j | , ^ g 2 5 ; p V. B. 50 Dr. Steinman Dr. Barbara Crockett Dr. Cooke Dr. Horvath Dr. Schafer Dr. Keichel Dr. Sternfeld Dr. Dr. Mewborn Dr. Hawkins Dr. Clark Dr. Schachner Dr. Susan K. Blew Dr. H. R. Melch Dr. Karamat Choudhry Dr. C. S. Patterson Dr. William Bernell Dr. Charles Crane Dr. R. K. Gaines Dr. W. L. Stewart Dr. H. B. Follander Dr. Stephen Youngberg Dr. Geesbrecht Dr. Dwight Pierson Dr. Allan Sonstein Dr. Rambie Briggs Dr. Steven J. Senevy Dr. James Aston If fl Danny Ford II II II II II II II II Jordan Family II IV II II II II II II II II II II II II II V. B. 52 w Dr. L. Lee Lankford Dr. James E. Way Dr. Philip Kingery Dr. Thomas 0. Tiernan Dr. I. L. Van Zandt Dr. V. Rhoades Dr. Funnell Dr. Hall Dr. Edward C. Rainey Dr. Stephen G. Maddox Dr. Hugh Warren Dr. Delvyn C. Case Dr. Keilet Dr. B. Voss Neal Dr. James E. Kopp Dr. Barry Salter Dr. John Q. A. Mattern Dr. Peter Law Dr. John Wirth Dr. George Sigalos Dr. George Brown Dr. Fred Mehlop Dr. Richard Kubick Dr. Robert DiNapoli Dr. Judith Chown Dr. Michael Sampson Dr. Wilten Fritz Treating Physician Lambiotte for David Treating physician Ryan V. B. 53 15652 Dr. Oscar Schwartz Dr. Ronald Carr Dr. Walter Silver Dr. Morton Glaser Dr. Bertram Cohen Dr. David Baker ROBERT S. McNAMARA JOHN ANGEL fl If If If II If * The above treating physicians have not yet been deposed and may be called either live or by way of deposition testimony to be taken in the future. 1800 K Street, Washington, D.C. 20006; Robert McNamara was Secretary of Defense, January 1961, through March, 1968; he will testify that he was unaware of any health hazards posed by 2,4,5-T and further that he neither had nor received any communication from other government agencies as to any health hazards of 2,4,5-T. And had he known of any health hazards, he would have pursued the matter. P.9 L.16 ; P.10 L. 14; P.11 L. 25; P.12 L.1-12; P.13 L.20-25; P.14 L.25 ; P.15 L.23 ; P.16 L.5; P.20 L. 1-8; P.21 L.22 ; P.22 L.9-14; P.22 L. 15; P.23 L. 4-15; P.23 L. 21-25; P.24 L.1-3; P.25 L.22; P.25 L.25; P.26 L. 1-4; P.26, L. 5-12; P.26 L.22-25; P.27 L. 1-1 - ; P.27 L. 16-19; P.28 L.25; P.30 L.1-11; P.30 L . 12-19; P.30 L.20-25; P.31 L. 1-4; P.32 L.18-19; P.32 L.24-25; P.34 L.1-4; P.35 L. 8-19; P.36 L.23-25; P.40 L.15-25; P.40 L.15-25; P.41 L. 1-9; P.42 L.24-25; P.43 L.1-5; P.44 L.13-23; P.45 L. 15-25; P.51 L. 10-25. Box 78, Yellville, Arkansas; Various titles over the years including Research Chemist at Jacksonville, Arkansas Plant of Reasor Hill Corporation, 1950-1959. 15S53 V. B. 54 GENERAL MAXWELL TAYLOR From 1950-1959, Mr. Angel was a research chemist at Reasor Hill Corp.'s Jacksonville Plant, where he analyzed materials and products, including, 2,4,5-T, and did process research work on the process for producing 2,4,5-T with Dr. Sidwell. During the period of 1950 - 1959, a number of herbicide production workers in the Jacksonville Plant had chloracne. During that period, he also learned of Monsanto's industrial accident in their 2,4,5-T process at Nitro, West Virginia, and learned of Thompson Hayward Chemical Co.'s industrial accident in their plant. He was aware that TCP caused chloracne several years before he began working with Thompson Chemical Co. in 1963. Deposition designations: P.10 L.16 - P.10 L.23; P.14 L.16 - P.15 L. 1 ; P.16 L. 1 - P.16 L.4; P.16 L. 17 P.17 L.9; P.17 L.25 - P.18 L.13; P.19 L.7 - P.20 L.3; P.21 L.5 - P.23 L.2; P.23 L.9 - P.24 L.25; P.29 L.3 - P.30 L.8; P.41 L.3 - P.41 L.15; P.56 L.18 - P.57 L.8. General Taylor was Chairman of the Joint Chiefs of Staff from 1962 through 1964 and was the Ambassador to Vietnam. Although General Taylor admits knowing of the defoliation program, he repeatedly asserted his lack of knowledge of the harmful effects of Agent Orange. He also repeatedly asserted that he never had any communications, to and from, concerning possible harmful effects of Agent Orange with either Federal Agencies or Chemical Companies. The Brief Cross-examination by defense attempted to establish that Gen. Taylor was more involved with policy rather than the overall conduct of the military operation. The distinction would tend to diminish the significance of his lack of knowledge and communication concerning Orange's harmful effects. Aside from this, the impact of his testimony was lack of knowledge of 1565* V. B. 55 the military. Disclaimer of knowledge prior to 1969. Gen. Taylor stated to the best of his recollection that he never heard of defoliation program being discussed either by Presidents Johnson or Kennedy. The witness became aware, sometime after 1962 while serving as Chairman of the Joint Chiefs, of the defoliation program and of the use of commercial herbicides. The program's purpose was to clear undergrowth to prevent ambush and to destroy food sources. Gen. Taylor stated that the defoliation program's purpose was not to harm human beings, American Personnel or Enemy. The witness stated that everone assumed that the herbicides deployed were non-toxic. He also did not recall if McNamara informed him of any possible harm posed by the herbicides. After becoming Ambassador to Vietnam in 1965, the witness along with McNamara, visited Vietnam at least 5 times. He reported that during these visits and attendant briefings at Westmoreland's Headquarters, there were no discussions concerning Americans becoming sick as a result of being in areas that were sprayed. Gen. Taylor responds that in his capacity as a military representative of the President and Chairman of the Joint Chiefs, he never received any information from any source of the harmful effects of deployed chemicals. Gen. Taylor further reported of not hearing complaints that herbicides were causing harm while serving as Ambassador to Vietnam from 1964 1965. Gen. Taylor was not aware of AAAS study which indicated that Orange could cause birth defects as of December, 1969. He was never during any of his positions advised by any Department of Agriculture Representative of the harmful effects of Orange. The witness, from 1966-1969, was President of the Institute of Defense Analysis. He had contact with Dr. McDonald and to 15655 V. B. 56 PAUL WARNKE the best of Gen. Taylor's recollection, he had no discussions with MacDonald and to the best of Taylor's recollection, he had no discussions with MacDonald concerning the harmful effects of Agent Orange or Dioxin. Witness reports not having oral or written communication with the following Government Agencies concering Orange's harmful effects: U.S. Public Health Service; Food and Drug Administration; Surgeon General; NCI; HEW; EPA; Edgewood Aresenal; Fort Detrick Crops Division; Advanced Research Project Agency; U.S.Army Chemical Corps., Naval Medical Research Institute; Marine Corps Chemical Branch; Air Force Systems Command. In his capacity as Ambassador to Vietnam, Gen. Taylor reports that he. was not advised concerning a Dow meeting in Midland, Michigan in 1965, to discuss chloracne problem associated with defoliation program. He expressly stated that he was never in contact at any time with any chemical company. P.12 L.21-25; P.13 L. 16-25; P.14 L . 10-18; P.15 L.13-25; P.17 L.22-25; P.18 L.22; P.20 L.24-25; P.21 L.1-6; P.21 L.18-22; P.28 L.11-25; P.24 L. 15-20; P.25 L.14-24; P.26 L.1-25; P.27 L.1-25; P.28 L.1-25; P.22 L.11-23; P.23 L.1-19. Mr. Warnke served as Assistant Secretary of Defense for International Security Affairs from 1967 to 1969. He testified to his lack of knowledge of any health hazards associated with Agent Orange. He further testified that in spite of his awareness of the Herbicide Program, he was unaware of the specific names of the herbicides. His testimony indicates that he was not informed specifically of all aspects of the herbicide program in his capacity as Assistant Secretary of Defense. It can be inferred, therefore, that Government knowledge of Agent Orange 15651> V. B. 57 Toxicity was minimal or fragmented within specific agencies. Mr. Warnke also testified about daily morning meeting with McNamara and there was no discussion of Orange's toxicity. He also testified as to his lack of communication to and from other government agencies concerning this matter. Mr. Warnke did not recall any issue arising regarding the use of herbicides in Vietnam while he was an Assistant Secretary for Defense from 1967 - 1969. He became aware that a herbicide program was being utilized in South East Asia, but was unaware who made the decision to deploy herbicides. He became aware of deployment program while serving as General Counsel in 1966-1967. Mr. Warnke wsa not aware that Agent Orange was a specific herbicide being deployed. In addition, he did not recall ever hearing the term while at the Defense Department. The witness reports of not receiving any notice either oral or written, from any chemical company, relating to defoliation agent's potential health hazards. He also reports not receiving any communication of adverse health effects of Agent Orange from any representative: 1) U.S. Public Health Service 2) FDA 3) Surgeon General 4) NCI 5)HEW 6) EPA 7) Edgewood Arsenal 8) Fort Detreick 9) The Advanced Research Project Agency 10) U.S. Army Chemical Corps. 11) The Naval Medical Research Institute 12) U.S. Marine Corps. Chemical Branch 13) Air Force Systems Command 14) or Interagency task force on the subject of herbicides or pesticides. Mr. Warnke also did not recall seeeing or reading a Rand Corp. report from 1967 that indicated the Herbicides were deadly to humans as well as to plants. He reported lack of personal knowledge of a December 29, 1967, Joint Chiefs of Staff report to McNamara that herbicides were non-toxic to humans. The witness recalls study being .565 V. B. 58 conducted relating to defoliation program's efficiency. However, he did not recall any conversation or investigation with regard to human beings. The witness was never assigned any project concerning the defoliation program in Vietnam and reported that to his knowledge, purpose of defoliation was never to harm humans. Mr. Warnke reported, based upon his experience of the general decision making process, that the decision to deploy herbicides would have emanated from the Joint Chiefs. The Joint Chiefs would have brought it to the Secretary of Defense, who would have brought it to the President. The ultimate decision to employ herbicides would be made by the President. Based upon his experience, decision with regard to any changes in the conduct of warfare during his tenure to the President. However, the witness did not know if ultimate decision was made by the President. He also reported that Secretary of Defense McNamara would hold daily morning staff meetings to discuss the War's progress and says that he discussed the herbicide program with Secretary McNamara. Mr. Warnke reports that the only hazards discussed at these daily meetings were the ecological or agricultural impact of the defoliation program. There were no discussions concerning health hazards to humans. Mr. Warnke recollected that there were never any discussions at these daily meetings concerning who established "Agent Orange" specifications, or whether the Chemical Companies met those specifications. No Governmental Agency or subdivision thereof ever advised Mr. Warnke of a possible health hazard to "Agent Orange". Although Mr. Warnke served under Presidents Johnson and Nixon, he does -not recall having any conversations with either President regarding Ageny Orange's possible toxicity to humans. He believes V. B. 59 15658 that the Secretary of Defense had authority to terminate or initiate defoliation and expressly stated that he didn't believe that anyone in lower levels had such authority. Secretary McNamara never told witness that he had received an ARPA Report indicating that deployed herbicides were toxic to humans. P. 10 L.6-14; P.11 L. 8-16; P.13 L. 11; P.13 L.25; P.19 L.16 - P.24 L.5; P.29 L.23 - P.30 L.14; P.31 L.8-16; P.32 L.11-18; P.39 L.4-7; P.48 L.17-22; P.11 L.19 - P.12 L.1; P.12 L. 8-15; P.15 L.23 - P.16 L.9; P.17 L.5 - 9; P.17 L.10-18; P.24 L.6-11; P.33 L.6-13; P.33 L.18 - P.34 L.9; P.35 L.14 - P.36 L.11; P.48 L.4-16. V. B. 60 VI ISSUES TO BE PROVED Plaintiffs are not required to present a statement of such issues with this submission at this time. A complete statement of issues to be proved will be filed in conformity with the Magistrate's Pre-trial Order No. 17. VI - 1 VII DISPUTED ISSUES OF FACT AND LAW Plaintiffs are not required to present a statement of such issues with this submission at this time. A complete statement of such issues will be filed in conformity with the Magistrate's Pre-trial Order No. 17. Respectfully Submitted, PLAINTIFFS' MANAGEMENT COMMITTEE By VII - 1 Exhibit #P0288 PIN # Date Author Addressee DS00017880 22-Apr-64 J S CORT CECIL & KENNEDY Description Memorandum from J. S. Cort, Jr. dated April 22, 1964 from J. S. Cort, Jr. to L. L. Cecil, Jr. reminding him that any materials returned from Columbia are to be inspected for tampering and samples taken for chemical testing. Exhibit #P0289 PIN # Date Author Addressee Description DS00018061 27-Apr-64 MARCELLUS POWERS QUEMOR LIMITADA & BONFIELD HOPKINS JACKSON JAMERSON Report dated April 27, 1964 from Hazelton Laboratories, Incorporated, Falls Church, V a . , to Quimor Ltda. concerning toxicology of samples furnished by Quemor. The Report, written by Dr. Marcellus Powers, DVM, concludes that the materials were, in fact, toxic. Exhibit #P0290 PIN # Date Author Addressee Description DS00017879 27-Apr-64 WARREN M ALGEO CECIL & SAVAGE HONOUR Memo dated April 27, 1964 from Warren M. Algeo, Columbia, to L. L. Cecil stating that the problem in Valle del Cruce is not as serious as in Modellin 1, and suggesting that if the latter problem could be resolved the problem would be in hand. Exhibit #P0297 PIN # Date DS00018059 01-Jun-64 IV. A. 21 1 15680 Author Addressee C W GILES HONOUR & PURDY Description Letter dated June 1, 1964 from Alexander & Alexander (C.W. Giles, AVP) to S. B. Honour at Diamond returning copy of Gecil letter and stating that the government report had been received and would be transmitted, but that it indicated that there was a product fault. Exhibit #P0299 PIN # Date Author Addressee Description DS00018081 02-Jun-64 D M PURDY CRICHLAY A & CORT HONOUR & KENNEDY MASAK Memorandum dated June 2, 1964 from D. M. Purdy to A. Critchlay concerning Product Liability claims in South America. The writer suggests that the problems in South America could be traced to a single batch. Otherwise, it is estimated that claims will be from $5,000 to $10,000. The writer suggests that distributors be advised that all claims should be reported to in surance carriers. Exhibit #P0301 PIN # Date Author Addressee DS00018057 04-Jun-64 CECIL CORT & HONOUR PURDY & SAVAGE Description Memo dated June 4, 1964 from Cecil to the File stating that Quimor's letter of May 15, 1964 was only a statement of what might happen after the government investigation was finished. The letter suggests that Quimor could sue, but really doesn't prefer that course of action. Exhibit #P0303 IV. A. 212 PIN # Date Author Addressee Description DS 17384 1O-Jun-64 JOHN WHITTLEMAN WILLIAM CARGO INTER OFFICE MEMO CHLORACNE COSTS Exhibit #P0304 PIN # Date Author Addressee Description DS 17383 12-Jun-64 W A CARGO C. R. BROWN MEMO REGARDING ANNUAL COSTS OF CHLORACNE Exhibit #P0309 PIN # Date Author Addressee DS00011398 15-Jul-64 J J PIRRONE CORT & BRUMBAUGH EVERSON & SCHULDT HONOUR & SAVAGE Description Memorandum dated July 15, 1964 from Pirrone to Cort reporting on negotiations with Cela to obtain know-how on reducing acnegin in TCP. Exhibit #P0317 PIN # Date Author Addressee Description DS00008800 21-Aug-64 VAN C CAYTON KENNEDY & CORT WILKERSON Memorandum from Van C. Cayton to F. R. Kennedy dated August 21, 1964 asking what data is available to substantiate claim on patent application that new TCP process reduces Chloracne causing com pounds . Exhibit #P0318 PIN # Date DS00017367 01-Sep-64 15662 IV. A. 213 Author Addressee Description C R BROWN TILLMAN & CORT KENNEDY & MASEK THOMPSON Memorandum dated September 1,1964 from C.R. Brown to A. B. Tillman and a large distribution list, advising that Dr. McBurney has sent along three articles on porphyria, which is old hat to Bleiberg and McBurney and some others, but which was new to himself and, he thought, to the addressees. States that this will be expensive in terms of insurance premiums. Reports hopefully on the efforts of John Cort to obtain know-how from a German company on the matter and of a forthcoming trip by Dr. McBurney to Germany at which a visit is to be arranged. Exhibit #P0321 PIN # Date Author Addressee Description DS 17367 1O-Sep-64 C R BROWN A. B. TILLMAN & J. S. CORT F. R. KENNEDY & E. J. MASON D. L. THOMPSON UNSIGNED MEMO DATED 091064 FROM BROWN TO TILLMAN, ET. AL. Exhibit #P0322 PIN # Date Author Addressee ILLEGIBLE 11-Sep-64 F R KENNEDY CAYTON & CLEVELAND CORT & WILKERSON Description Memorandum from Kennedy to Cayton in response to his inquiry of August 31 seeking backup data on statement in patent application and stating that pre-1960 data was too poorly kept to be able to produce charts showing changes in health experience after using the new process. Exhibit #P0328 IV. A. 214 .566 3 PIN # Date Author Addressee Description DS00018205 21-Oct-64 B KRIENKE CHEMICAL BANK St LEON CHANG MORRIS ABE Letter from B. Krienke, Agricultural Chemicals, Diamond Shamrock to Chemical Bank, dated October 21, 1964, instructing the bank to accept $6,045.60 4,570.50 against a $10,616.10 draft due to a credit for returned materials. A postscript to the letter, signed by Morris Abe, states that Quimor Ltda. is entitled to a credit for 1,000 gallons of of 2,4-D and 2,4,5,-T herbicides. Exhibit #P0330 PIN # Date Author Addressee Description DS00022683 06-Nov-64 D J PORTER EVERSON & GALLOWAY LIMPEL & MCCALLAN SCHULDT Memorandum dated November 6, 1964 from D. J. Porter to a distribution list forwarding a letter of the same date from Porter to Contracting Officer, U.S. Army, Biological Laboratories, Fort Detrick, sending proposal to participated in a one year study of the effects on biological activity of combining a number of chemical herbicidal compounds and adjuvants, as per an invitation letter dated October 9, 1964. Letter brags about facilities available for the project. Exhibit #P0337 PIN # Date Author Addressee DS00017997 04-Dec-64 S B HONOUR GILES Sc CORT PURDY Sc SAVAGE Description Memorandum dated December 4, 1964 from S. B. Honour to C. W. Giles, Assistant Vice President of Alexander Sc Alexander, Inc. Acknowledges receipt of November 24, report letter, and states that it would be a ,, _ . lbbo4 IV. A. 215 m i s t a k e f o r t h e AFIA r e p r e s e n t a t i v e t o s e t t l e i n d i v i d u a l w o rk ers' claim s and t h a t Quimor had a p o i n t in s u g g e s t i n g settlem ents' with the employers. Exhibit #P0347 PIN # Date Author Addressee DS 17978 28-Dec-64 C W GILES R F INGEGNERI Sc LEGAL DEPT AMER. FOREIGN INS. & ASSN. Description LTR FROM GILES TO INGEGNERI RE BOGOTA CLAIMS D.A. Exhibit #P0348 PIN # Date Author Addressee Description DS 17980 29-Dec-64 C W GILES S. B. HONOUR & DIV. SALES MANAGER DIAMOND ALKALI LETTER REGARDING PRODUCTS LIAB. BOGOTA, COLOMBIA Exhibit #P0354 PIN # Date Author Addressee Description DS 22677 13-Jan-65 P H SCHULDT FILE Sc L E LIMPEL D J PORTER SIGNED COPY INTER OFFICE CORRES. 1/13/65 Exhibit #P0384 PIN # Date Author Addressee DS00018145 08-Mar-65 S B HONOUR QUIMOR LTDA St GUILLERMO LEON GILES & PURDY Description Letter dated March 8, 1965 from Honour to Quimor forwarding check for claims and requesting a quitclaim. 15665 TT7 A 71 fi Exhibit #P0407 PIN # Date Author Addressee DS 379 VME1M9RK-M.MEaRRTOrAW-YK6MEE5LOLNYD MVDERH5OcEZDER. J5c. MWR.ILKFRENAFNECLIDS KENNEDY DR. ED CHANDLER & DR. JOHN P. FRAWLEY Description LTR OF ROWE TO KELLY ET. AL. RE 2,4,5-T MEETING. Exhibit #P0411 PIN # Date Author Addressee DS 12615 JJ2EO.5H-LNM0aC. rHC-AOK6RNIN5TDGLJERR5.c M5.c FF..PW. ILKKENERNSEODNY Description 1-0 MEMO RE 3/24/65 MEETING ON 2,4,5-T TOXIC IMPURITIES. Exhibit #P0421 PIN # Date Author Addressee Description 12609 30-Mar-65 F R KENNEDY J R CORT, JR. 1-0 MEMO RE CHLOROACNE DOW MEETING. Exhibit #P0429 PIN # Date Author Addressee Description DS00018120 27-Apr-65 C W GILES HONOUR & PURDY DIAMOND ALKALI Letter dated April 27, 1965 from C. W. Giles. AVP Alexander & Alexander to S. B. Honour of Diamond Alkali paying $1,611.90 in reimbursement for Quimor claims. IV. A. 217 *J O U ! Exhibit #P0430 PIN # Date Author Addressee Description DS 17355 27-Apr-65 T S JR CORT F R KENNEDY MEMO OF 4/27/65 FROM CORT TO KENNEDY RE CHLORACNE. Exhibit #P0440 PIN # Date Author Addressee Description DS 24633 11-Jun-65 W A GOODLOE MR. E. BAK MONTHLY REPORT FOR MAY 1965 Exhibit #P0446 PIN # Date Author Addressee Description DS00024548 09-Jul-65 W A GOODLOE BAK Memorandum dated July 9, 1985 from W. A. Goodloe to E Bak reporting chroraotographic assays of residuals after filtering TCP. Report shows that 10% solfiltration is required to keep residual below 1ppm. Exhibit #P0447 PIN t Date Author Addressee Description 0000 09-Jul-65 W A GOODLOE E. BAK MONTHLY REPORT JUNE 1965 RE P-DIOXIN PROJECT. Exhibit #P0449 PIN # Date Author Addressee DS 18090 15-Jul-65 GEORGE RATHGABER S.B. HONOUR & SALES MANAGER DIAMON ALKALI & D.M. PURDY IV. A. 218 fcTn dt) ] Description LETTER RE PRODUCTS LIABILITY, BOGOTA COLOMBIA Exhibit #P0460 PIN # Date Author Addressee Description DS 2454 20-Sep-65 W A GOODLOE LABORATORY ANALYSIS REPORT RE T-ACID LEVELS. Exhibit #P0466 PIN # Date Author Addressee DS00018235 19-Nov-65 LEON R GUILLERMO COPETE ALBERTO & AFIA COLIMBIANO LTD DIAMOND INTERAM & RESTREPO HUMBERTO Description Letter from Quimor, Ltd. to AFIA Colombian, Limited, dated November 19, 1965 outlining complaints in relation to the toxicity of the product, which it had independently tested Hazeltine, and outlining the dollar value of its complaint. Exhibit #P0477 PIN # Date Author Addressee DS00018227 0B1B-FHebO-N6O6UR QUIMOR LIMITADA & GUILLERMO Description Letter dated February 1, 1966 from S. B. Honour to Guillermo Leon R. of Quimor Limitada, stating that his January 28 letter was received and that it has been brought to the attention of Mr. Savage, General Manager-International Division and Mr. J.S. Cort, Jr., General Manager Agricultural chemicals Division, and stating that they have to wait for Mr. Savage to come back from a trip before they can give him an answer. IV. A. 219 Exhibit #P0481 PIN # Date Author Addressee DS00024628 23-Mar-66 W A GOODLOE STEWARD & KENNEDY Description Memorandum dated March 23, 1966 from W. A. Goodloe at Newark to F. G. Steward reporting on analysis of TCP using different filtration methods. Shows production TCP evidenced levels of 56 to 10 ppm, from December of 1965 through March of 1966. The Memorandum also shows that dilution results in minimal dioxin content. The Memo is denominated an "Interim Report." Exhibit #P0482 PIN # Date Author Addressee Description DS 24628 23-Mar-66 W A GOODLOE F. G. STEWARD INTERIM REPORT DIOXIN STUDY. Exhibit #P0483 PIN # Date Author Addressee Description DS00012690 06-Apr-66 J C KELLY KING & KENNEDY GUIDI Memorandum dated April 6, 1966 by J. C. Kelly to J. 0. King reporting that after submitting a sample of technical 2,4,5-T , Dow said they would not buy it because they felt that using Diamond's material would resurrect their chloracne problem. Exhibit #P0496 PIN # Date Author Addressee Description DS 21663 30-Jun-66 UNKNOWN ASSIGNMENT OF PATENT PERKINS ET AL TO DIAMOND ALKALI IV. A. 220 15659 Exhibit #P0501 PIN # Date Author Addressee Description DS 951 13-Jul-66 F GORDON STEWARD OPERATING COMMENTS JUNE, 1966. Exhibit #P0512 PIN # Date Author Addressee Description DS 967 07-Sep-66 E BAK OPERATING COMMENTS 1966. PRODUCTION - AUGUST, Exhibit #P0522 PIN # Date Author Addressee Description DS00021969 12-Oct-66 BOEHRINGER WARBURGTON & DIAMOND CLEVELAND Letter from C. H. Boehringer Sohn dated October 12, 1966 to Diamond threatening to challenge a proposed patent unless Diamond signs a stipulation (not annexed to the exhibit). Exhibit #P0542 PIN # Date Author Addressee Description DS1005 23-Nov-66 R A GUIDI F . R. KENNEDY & R. L. URBANOWSKI GORDON STEWARD MONTHLY TECHNICAL REPORT. Exhibit #P0558 PIN # Date ILLEGIBLE 09-Jan-67 IV A. 221 1 'C/-> r* i Author Addressee JJ LUSARDI STEWARD h KENNEDY BAK & GOODLOE Description Memorandum dated January 9, 1967 from J. J. Lusardi to F. G. Steward, reporting on experiments with different types of filters in an attempt to remove the 2,3,7,8-TCDD impurity from the production line. Exhibit #P0559 PIN # Date Author Addressee DS23332 09-Jan-67 J J LUSARDI F G STEWARD & F R KENNEDY E BAK & W A GOODLOE Description INTERIM REPORT OF EXPERIMENTAL WORK FOR TCP PURIFICATION. Exhibit #P0585 PIN # Date Author Addressee DS 3367 20-Feb-67 J S JR CORT FILE & R A GUIDI Description RESUME OF "ORANGE" NIAGARA FALLS MEETING 2/17/67. Exhibit #P0608 PIN # Date Author Addressee Description DS00001046 12-Apr-67 F GORDON STEWARD Staff document originated by F. Gordon Steward and dated April 12, 1967 which outlines operations at the 2,4-D and 2,4,5-T lines. States that the TCDD removal filtration system is successful and that the carbon filter is being tested for further evaluation. 1 'O i i, IV. A. 222 Exhibit #P0628 PIN # Date Author Addressee Description DS00001074 07-Jun-67 F GORDON STEWARD Staff Memorandum by F. Gordon Steward reporting on technical operations for the month of May, 1967. Reporting on a continuing effort to evaluate the effectiveness of different filtration systems, the report states that the use of small disposable filters as the primary means of TCP purification does not appear possible and that the filters still plug up rapidly. The use of a carbon filter, although it too plugs, is being considered and shows some promise. Heating in the vicinity of the plub did not see seem to work. Exhibit #P0642 PIN # Date Author Addressee DS00016917 12-Jul-67 F R KENNEDY CORT & GUIDI Description Technical Memo examines recently issued specification for Agent Orange. Dated July 12, 1967. Principal complaint is that by requiring mixing to be done by volume instead of weight, Diamond will have to come up with more "T" in the mixture than it had planned. Refers to a previous document issued by Newark, possibly a draft specification. Exhibit #P0643 PIN # Date Author Addressee Description DS00001084 12-Jul-67 F GORDON STEWARD Staff Memorandum prepared by F. Gordon Steward on July 12, 1967. With regard to filtration of TCP, states that experimental tower has been set up and seems to be working and that tests were being conducted to see what the saturation point of the carbon filters were so that cycles could be "*'n, w i t IV. A. 223 i designed. Exhibit #P0645 PIN # Date Author Addressee Description DS 23266 20-Jul-67 D R GEAMAN F.G. STEWARD & F.R. KENNEDY E. BAK & W. A. G00DL0E L.M. SZENDREY 1-0 CORRES. RE FILTRATION OF CHLORACNEGENS FROM 10% TCP. Exhibit #P0648 PIN # Date Author Addressee Description DS 1095 09-Aug-67 F GORDON STEWARD OPERATING COMMENTS PLANT TECHNICAL JULY 1967. Exhibit #P0668 PIN # Date Author Addressee Description DS00001107 13-Sep-67 F GORDON STEWARD Staff memorandum prepared by F. Gordon Steward on or about September 13, 1967. Reports that an analysis of the last runs made at the lab column showed that it was removing the dioxin from the TCP and that, under laboratory conditions, the effluent from the tower benzine in the wash could remove 75% of the dioxin from 10 times its volume of effluent. In a plant setting, they would expect 5 times the ration, and it was concluded that this was not acceptable, so the program was being scrapped. Exhibit #P0680 PIN # Date DS00001119 11-Oct-67 IV. A. 224 Author Addressee Description F GORDON STEWARD Staff Memorandum concerning plant technical operations prepared by F. Gordon Steward on October 11, 1967. Report indicates that plant purification unit is operating successfully, producing TCP with dioxin contents of less than 1ppm. States that a real control on this factor was delayed because instrumentation was not completed in the new facility. Exhibit #P0688 PIN # Date Author Addressee DS00018206 31-Oct-67 S S SAVAGE HONOUR & SARREY Description Memorandum from S. S. Savage dated October 31, 1967 in Bogota to S. B. Honour stating that ROBLEDO HERMANOE is the last claim from the debacle and that, although AFIA is handling their claim, there is the matter of two 55-gallon drums that they were holding for evidence and that they want to return. Savage reports that he assured Quimor that they would "work something out" if they had to credit the customer. Exhibit #P0692 PIN # Date Author Addressee Description DS00001129 08-Nov-67 F GORDON STEWARD Staff Report prepared on November 8, 1967 by F. Gordon Steward concerning technical operations at the Newark Plant. Under "TCP" it is reported that the carbon tower was converted from a batch operation to a flow operation, but through use of a specific gravity controller. TCP flow was controlled manually and tended to plug up. Checks of dioxin levels made during the month were reported to be "satisfactory." IV. A. 225 rpi'pn's>-*c>' 4 Exhibit #P0696 PIN # Date Author Addressee DS 2917 1O-Nov-67 R A GUIDI F. R. KENNEDY & J.C. KELLY Description 1-0 MEMO FROM GUIDI TO KENNEDY - SEND "ORANGE" SAIGON. Exhibit #P0719 PIN # Date Author Addressee Description DS 1156 1O-Jan-68 F GORDON STEWARD OPERATING COMMENTS PLANT TECHNICAL DEC.. 1967. Exhibit #P0736 PIN # Date Author Addressee Description DS00001169 07-Feb-68 F GORDON STEWARD Staff Memorandum prepared on February 7, 1968 by F. Gordon Steward concerning technical operations at the Newark plant. The Memorandum reports that, although the TCP purification unit continued to operate in a satisfactory manner mechanically, they were continuing to get higher-than-desiredp-dioxin levels, averaging 3.0 in ppm in January and 2.8 ppm in December. Exhibit #P0745 PIN # Date Author Addressee Description DS00003446 26-Feb-68 F R KENNEDY GUIDI Memorandum dated February 26, 1968 from F. R. Kennedy to R. A Guidi concerning residues collecting in the dump pit north of the Process Building. States an analysis showing dioxin levels of 75 ppm, and another dioxin of 16.6 ppm. Notes precautions being taken with workers at site. Also says that the assay is about IV. A. 226 1 u'r the same as the TCDD content of Diamond's production TCP before the "clean up." States that this will go down as the clean up progresses. Exhibit #P0764 PIN # Date Author Addressee Description DS00001206 08-May-68 F GORDON STEWARD Staff Memorandum dated May 8, 1968 and prepared by Gordon Steward. Gordon Steward summarizing plant operations from a technical point of view during the month of May, 1968. The Memorandum reports that the operation of the TCP purification unit "satisfactory", with dioxin levels running at about 1.8 ppm average for the month. The principal contaminants are reported to be, still, "unknowns." Exhibit #P0777 PIN # Date Author Addressee Description DS 1219 11-Jun-68 F GORDON STEWARD OPERATING COMMENTS, PLANT TECHNICAL, MAY, 1968. Exhibit #P0796 PIN # Date Author Addressee Description DS 1253 11-Sep-68 F GORDON STEWARD OPERATING COMMENTS, PLANTS TECHNICAL, AUGUST, 1968. Exhibit #P0806 PIN # Date Author Addressee DS 17181 04-Oct-68 M F WILKERSON H. HOCHBERG & J.A. WILSON IV. A. 227 Description R. A. GUIDI & C. L. TROPH J. 0. KING 1-0 CORRESPONDENCE TASK FORCE MEETING WELDON SPRINGS. Exhibit #P0819 PIN # Date Author Addressee Description 19437 03-Dec-68 R W MD MC BURNEY WILLIAM F. BARTHAL & DEPT HELTH, EDUC. WELFARE HOW TO ASSIST RE PORPHYRIA CUTANEA TARDA & CHLORACNE. Exhibit #P0820 PIN # Date Author Addressee Description DS00001285 11-Dec-68 F GORDON STEWARD Staff Memorandum on Newark technical operations for the month of November, 1968 prepared by F. Gordon Steward on or about December 11, 1968. The cleaning tower for TCP did not work well and was producing 9.3 ppm after cleaning. The carbon bed was to be replaced when materials were received. The memorandum reports on efforts to analyze dirt around the plant for dioxin and also to divert contamination from vents at the TCP unit area. Exhibit #P0832 PIN # Date Author Addressee Description 1297 07-Jan-69 F GORDON STEWARD OPERATING COMMENTS, PLANT TECHNICAL, DECEMBER, 1968. Exhibit #P0841 PIN # Date DS000247 24 12-Feb-69 IV. A. 228 iti'D i ( Author Addressee Description F GORDON STEWARD Staff Report on Plant Technical Operations for the Month of January, 1969 , prepared by F. Gordon Steward on or about February 12, 1969. Under the heading "TCP" it is reported that the dioxin content at the tower was greater than 10 ppm, which was reduced to less than 1 ppm after changing the carbon bed. Exhibit #P0842 PIN # Date Author Addressee Description 24724 12-Feb-69 F GORDON STEWARD OPERATING COMMENTS, PLANT TECHNICAL, JANUARY, 1969. Exhibit #P0857 PIN # Date Author Addressee Description 10302 13-Aug-69 F GORDON STEWARD OPERATING COMMENTS PLANT TECHNICAL JULY 1969. Exhibit #P0866 PIN # Date Author Addressee DS 24611 24-Nov-69 R A GUIDI F G STEWARD & F. R. KENNEDY Description 1-0 CORRES. NEWARK PLANT HEALTH SURVEY MAN. FOR PUBL. Exhibit #P0882 PIN # Date Author Addressee Description DS00024544 23-Dec-69 F GORDON STEWARD KENNEDY Memo dated December 23, 1969 from F. Gordon 15678 IV. A. 229 Steward at Newark to F. R. Kennedy at Cleveland reciting history of efforts to identify and eliminate the chloracnegen, now known to be TCDD , from their TCP. Shows dioxin content by quarters from 1968 through 1969, disclosing that in December of 1968 the product had a 9 ppm which the report argues was due to a labor-management dispute that caused the carbon tower not be to be cleaned. Exhibit #P0969 PIN # Date Author Addressee Description DS 12557 22-Jul-70 F R KENNEDY DR. JACOB BLEIBERG LTR FROM KENNEDY TO BLEIBERG NOTING FREQUENCY OF SYMPTOMS Exhibit #P0971 PIN # Date Author Addressee Description 12558 04-Aug-70 JACOB BLEIBERG, MD DIAMOND SHAMROCK LTR FROM BLEIBERG TO KENNEDY RE "PERMANENT DISEASE" Exhibit #P1008 PIN # Date Author Addressee Description DS 17442 25-Jun-71 DL THOMPSON C. T. BALDEMA & C . R. BROWN F. G. STEWARD & C . H. GILBERT F. I. SCHICK 1-0 MEMO RE NEWARK WORKMEN'S COMPENSATION Exhibit #P1045 PIN # Date Author 10526 25-Jun-73 E A LAVERGNE IV. A. 230 Addressee DR. HANS KOCH Description LTR STATED USE OF DR KOCH" S PATENTED PROCESS. Exhibit #P1053 PIN # Date Author Addressee Description DS24599 22-Nov-75 F GORDON STEWARD D.M. PURDY & F. R. KENNEDY R. W. MC BURNEY 1-0 MEMO N.J. STATE DEPT. OF HEALTH SURVEY FORMER PERSONNEL Exhibit #P1088 PIN # Date Author Addressee Description 00000 18-Apr-80 UNKNOWN DEPOSITION OF A.E. SIDWELL TAKEN 4/18/80 IV. A. 231 15680 Exhibit #P0030 PIN # Date Author Addressee Description C 61055 G J MACLEAN DAVIDSON J H Article by G. J. MacLean and J. H. Davidson, Research and Development, Chemical Company, re: Diagnosis of Disorders in Pastured Livestock. Dow Exhibit #P0031 PIN # Date Author Addressee Description C052415 VI AINSLEE CANADA CUSTOMS Form prepared by Uniroyal (1966) Ltd., Chemical Division, Elmira, Ont. for Canada Customs for shipment of 126 drums (6868.26 gals) via C.N.R. to Gulf Outport, Mobile , Alabama. Exhibit #P0032 PIN # Date Author Addressee Description J 668 GEORGE F COLLINS UNITED STS RUBBER CO & DCASR Contract for herbicides (Incomplete). Exhibit #P0033 PIN # Date Author Addressee Description J 936 UNKNOWN UNKNOWN Incomplete contract for purchase of herbicides with Uniroyal Chemical Div. of Uniroyal , Inc., undated. Exhibit #P0034 PIN # Date Author ooo UNKNOWN 15681 Addressee Description Contract between Thompson Chemical & US & all extensions or renewals concerning the furnishing of AO or any herbicide containing 2,4,5-T to US government. (THESE DOCUMENTS ARE NOT YET AVAILABLE, BEING OBTAINED THROUGH CUSTODIAN OF RECORDS OF US GOVERNMENT. CONTRACTS ARE DATED 4/19/67 & 5/2/68.) Exhibit #P0035 PIN # Date Author Addressee Description THOMPSON-15 UNKNOWN Organizational chart of Thompson-Stearns-Rogers project (Weldon Springs Chemical Plant). Exhibit #P0036 PIN # Date Author Addressee Description THOMPSON-16 UNKNOWN Curriculum vitae of various players involved in Thompson-Stearns-Rogers project (Weldon Springs). Exhibit #P0037 PIN # Date Author Addressee Description 0002 R L DRUVA Sundry notes of Stern-Rogers showing the total knowledge on part of Thompson-Stearns-Rogers people concerning dioxin and its potential adverse health effects. Exhibit #P0038 PIN # Date 0003 IV. ,A. 233 15682 Author Addressee Description UNKNOWN Notes on conversations and interviews by Environmental Protection Agency, document 192059, subject; Thompson Chemical Company", revealing interviews by agents of the EPA of the United States govt, concerning waste disposal and going into knowledge of Thompson Chemical concerning 2,4,5-T. Exhibit #P0039 PIN # Date Author Addressee Description JUS0071 UNKNOWN Unidentified handwritten colums of figures. document with Exhibit #P0132 PIN # Date Author Addressee Description THOMPSON-11 17-Jan-60 F VARGAS Notes of meetings dated January 17, 1960 concerning concerning 2,4,5-T and the fact that dioxin is produced as a bi-product of 2,4,5-T, causing "chloracne and liver damage." Exhibit #P0144 PIN # Date Author Addressee Description C 61054 22-Jul-60 UNKNOWN ELMIRA, ONT. & 5 Page 7 of memorandum re:hygene. Exhibit #P0241 PIN # Date Author Addressee J 4279 19-Jul-63 UNKNOWN 15683" IV. A. 234 Description Military Specification for Herbicide: n-butyl 2,4-Dichlorophenoxyacetate, dated July 19, 1963. Exhibit #P0242 PIN # Date Author Addressee Description JUS0056 19-Jul-63 UNKNOWN UNKNOWN Military specificatin for normal butyl ester of 2,4-D dated July 19, 1963. Exhibit #P0271 PIN # Date Author Addressee Description 021565 15-Feb-64 W BRAUN BUCKELY Cover slip for translation of W. Braun article done on May 27, 1966 of article written in 1959 by Trans. Chem Inc. Exhibit #P0451 PIN # Date Author Addressee Description C056196 10-Aug-65 T H EVANS GRD & HAT WYH & TDM CRH & OTHERS Memo dated August 10, 1965 reporting on visit to Dow facility in Midland by T. H. Evans. Bears "Received" stamp of A.L.Gorman. Exhibit #P0514 PIN * Date Author Addressee Description J 469 23-Sep-66 JOHN EVANS UNITED STATES Herbicide contract DSA-400-67-C-1635 between USA and United States Rubber Company Chemical Div. for 150,000 gallons to be delivered on or before June 1, 1967, IV. A. 235 with all attachments Exhibit #P0518 PIN # Date Author Addressee Description J 253 H0D6CJ-AOScRFtIC-H6St6TDISBURSING OFFICE Acceptance form for 5451 gallons herbicide. Exhibit #P0519 PIN # Date Author Addressee Description J 265 06-Oct-66 H J FICHT DCASR St DISBURSING Acceptance form for dated Oct. 6, 1966. OFFICER 5451 gals, herbicide Exhibit #P0520 PIN # Date Author Addressee Description J 241 06-Oct-66 H J FICHT DCASR & DISBURSING OFFICE Acceptance Form dated Oct. 6, 1966 for 5451 gals, of herbicide. Exhibit #P0521 PIN # Date Author Addressee Description J 228 07-Oct-66 H J FICHT DCASR & DISBURSING OFFICER Acceptance dated October 7, 1966 for 5451 gallons of herbicide. Exhibit #P0523 PIN # Date Author Addressee Description J 220 17-Oct-66 H J FICHT DCASR St DISBURSING OFFICER Acceptance form dated October 17, 1966 for o cr \j :: IV. A. 236 5451 gallons of designated herbicide. Exhibit #P0524 PIN # Date Author Addressee Description J 21 1 17-Oct-66 H J FICHT DCASR & DISBURSING OFFICER Acceptance form dated October 17, 1966 for 5451 gallons of designated herbicid. Exhibit #P0528 PIN # Date Author Addressee Description J 202 25-Oct-66 R J JEFFERY DCASR & DISBURSING OFFICER Acceptance form for 5451 gallons of designated herbicide dated October 25, 1966. Exhibit #P0529 PIN # Date Author Addressee Description J 196 01-Nov-66 H J FICHT DCASR & DISBURSING OFFICER Acceptance of 5451 gallons of designated herbicide dated November 1, 1966. Exhibit #P0530 PIN # Date Author Addressee Description J 190 01-Nov-66 H J FICHT DCASR & DISBURSING OFFICER Acceptance Form for 5451 gallons of herbicide dated November 1, 1966. Exhibit #P0531 PIN # Date Author J 184 01-Nov-66 H J FICHT IV. A. 237 561 QO Qo Addressee DCASR & DISBURSING OFFICER Description Acceptance Form for 5451 gallons of herbicide dated November 1, 1966. Exhibit #P0536 PIN # Date Author Addressee Description J 177 H0DB9OCJ-SATNSOoRFNvIC-H6&6TDISBURSING OFFICER Acceptance form for 5451 gallons of herbicide dated November 9, 1966. Exhibit #P0537 PIN # Date Author Addressee Description J 171 09-Nov-66 H J FICHT DCASR & DISBURSING OFFICE BOSTON Acceptance of 5451 gal of herbicide dated November 9, 1966. Exhibit #P0538 PIN # Date Author Addressee Description J 165 09-Nov-66 H J FICHT DCASR & DISBURSING OFFICER BOSTON Accpeptance of 5451 gals of herbicide dated November 9, 1967. Exhibit #P0539 PIN # Date Author Addressee Description J 159 2H1J-NoFvIC-H66T DCASR & DISBURSING OFFICER BOSTON Acceptance for 5451 Gallons of herbicide dated November 21, 1966. IV. A. 238 Exhibit #P0540 PIN # Date Author Addressee Description J 153 H2DB1OCJ-ASTNSORoFNvIC-H6St6TDISBURSING OFFICER Acceptance for 5451 gals of herbicide dated November 21, 1966. Exhibit #P0541 PIN # Date Author Addressee Description J 147 21-Nov-66 H J FICHT DCASR St DISBURSING OFFICER BOSTON Acceptance for 5451 gals of herbicide dated November 21, 1966. Exhibit #P0543 PIN # Date Author Addressee Description J 141 28-Nov-66 H J FICHT DCASR St DISBURSING OFFICER BOSTON Acceptance form for 5451 gallons of herbicide dated November 28, 1966. Exhibit #P0544 PIN # Date Author Addressee Description J 135 HDB2O8CJ-SATNSOoRFNvIC-H6St6TCONTRACTING OFFICER Acceptance form for 5451 gallons of herbicide dated November 28, 1966. Exhibit #P0545 PIN # Date Author Addressee J 129 28-Nov-66 H J FICHT DCASR St DISBURSING OFFICE IV. A. 239 1Q BOSTON Description Acceptance for 5451 gals of herbicide dated November 28, 1966. Exhibit #P0546 PIN # Date Author Addressee Description J 123 H2DBO8CJ-SATNSORoFNvIC-H6&T6 DISBURSING OFFICER Acceptance form dated November 28, 1966 for 5451 gallons of herbicide. Exhibit #P0550 PIN # Date Author Addressee Description J 117 0HDB5OC-JSATDSOeRFNcIC-H65c6T DISBURSING OFFICE Acceptance form for 5451 gals of herbicide dated December 3, 1966. Exhibit #P0551 PIN # Date Author Addressee Description J 111 0HDB5OC-JSATDSOeRFNcIC-H65c6T DISBURSING OFFICE Acceptance form dated December 5, 1966 for 5451 gallons of herbicide. Exhibit #P0552 PIN # Date Author Addressee Description J 104 06-Dec-66 HBDOCJSATSORFNICH5cT DISBURSING OFFICE Acceptance for 7523 gallons of herbicide dated December 6, 1966. Exhibit #P0561 PIN # Date Author Addressee Description DOW751871 15-Jan-67 V K ROWE BUCKLEY & MC COY DIXON & HOLDER SILVERSTEIN Letter dated February 15, 1967 from V. K. Rowe to M.S. Buckley forwarding translations of "Clinical Observations About The Origin of Chloracne" and "Industrial Poisoning in the Manufacture of Chlorophenol Compounds". Mr. Rowe states he believes the reference to 2,4-D is incorrect and that the problem is confined to 2,4,5-T. Exhibit #P0568 PIN # Date Author Addressee Description J 657 27-Jan-67 GEORGE F COLLINS FAIRCLOUGH, W A & US RUBBER CO Negotiated Contract for 40,000 gallons of herbicide dated January 27, 1967 to be delivered on or before March 31, 1967. Exhibit #P0574 PIN # Date Author Addressee Description DOW 751874 03-Feb-67 WJ MCCOY ROWE, V.K. & CORBIN, W.L. PLETCHER, D.E. & GOWELL, J.H. Dow document 751874 memo dated 02-03-67 from McCoy to Roe, subject "Thompson Chemical Company", which included notation that Buckley of Thompson had phoned asking for recommendations for medical treatment for employees believed suffering from chloracne contracted during manufacture of 2,4,5-T. Exhibit #P0575 PIN # Date DOW751874 03-Feb-67 IV. A. 241 Author Addressee Description W J MC COY ROWE & CORBIN FLETCHER & GOWELL Memo dated February 3, 1967 from W. J. Me Coy to V. K. Rowe reporting that M. S. Buckley of Thompson Chemical had phoned asking for reporting a severe chlorancne problem and saying they were using Hooker's TCP. Asked for Dow's recommendations re: medical treatment. Notes they are a competitor but maybe advice would be be in order. Exhibit #P0581 PIN # Date Author Addressee Description 751872,3 15-Feb-67 VK ROWE DIXON, WILLIAM E' & CORBIN, W . L . ` PLETCHER, D.C. & COWELL, J.H. MCCOY, W.J. & HOLDER,B. B. Dow Doc. No. 751872 memo dated 02-05-67 from Rowe to Dixon of Dow re: internal memo relating Marion Buckley's phone call asking for info & guidance in cleanup after trichloraphenol accident. Exhibit #P0582 PIN # 751871 Date 15-Feb-67 Author VK ROWE Addressee BUCKLEY, M.S & MCCOY, W.J. DIXON, W.R. & HOLDER, B.B. M.D. SILVERSTEIN, L. Description Exhibit #P0583 PIN # Date Author Addressee Description DOW751872 15-Feb-67 V K ROWE DIXON & CORBIN FLETCHER & GOWELL MC COY & HOLDER Memorandum dated February 15, 1967 from V. K. Rowe to William E. Dixon, Bioproducts Division, reporting on calls from Buckley for help. Asked for advice and help on IV. A. 242 what to do in cleaning up instruments, and was given limited information. Also received articles in the public literature. Did not ask for information on how assay of residuals made, so did not volunteer. Similarly, had little understanding of total toxicological activity, and so it was not volunteered. Exhibit #P0599 PIN # Date Author Addressee Description J 761 21-Mar-67 GEORGE F COLLINS US RUBBER CO & DCASR Change to Contract DSA-400-67-C-5959 dated March 21, 1967 making Chief, DCASD, Hartford, Conn.., the contracting officer. Exhibit #P0611 PIN # Date Author Addressee Description UNKNOWN 19-Apr-67 GEORGE F COLLINS MITCHELL & THOMPSON CHEMICALS Herbicide contract dated April 19, 1967. Exhibit #P0615 PIN # Date Author Addressee Description J 899 02-May-67 GEORGE F COLLINS UNIROYAL CHEMICAL Modification of contract dated May 2, 1967 changing specifications for drum markings. Exhibit #P0616 PIN # Date Author Addressee Description J 95 1O-May-67 H J FICHT DCASR & DISBURSING OFFICE BOSTON Acceptance for 5451 gallons of herbicide dated May 1U, 1967. IV. A. 243 Exhibit #P0865 PIN # Date Author Addressee Description 0003 22-Nov-69 T A TREGLIA THOMPSON-STEARNS & ROGER, INC. JOHN GERETY, US ARMY Letter from T. A. Treglia to Thompson-Stearns-Roger, Inc. dated Nov. 22, 1968 concerning the Weldon Springs Project. Exhibit #P0958 PIN # Date Author Addressee Description C 61149 09-Jun-70 T D MURPHY WATT BERRY J & GREEN CROSS PRODUCTS SHERWIN-WILLIAMS CA & MONTREAL,QUE Letter dated June 9, 1970 from T. D. Murphy to Berry J. Watt of Green Cross Products of Sherwin- Williams of Canada, Ltd. discussing that the 1 ppm standards originated with equipment limitations and that it is not a government standard. Exhibit #P0963 PIN # Date Author Addressee Description C 61052 15-Jun-70 E WANLESS THOMSON H A & UNIROYAL LTD. CHEMICAL DIVISION & ELMIRA, ONTARIO Methodology for detecting residues. Exhibit #P0965 PIN # Date Author Addressee Description C 61051 23-Jun-70 WP COCHRANE THOMSON HUGH & CONTROL CHEMIST UNIROYAL LTD. & ELMIRA ONT. Reply to inquiry re: residues. Exhibit #P0973 IV. A. 249 Exhibit #P0617 PIN # Date Author Addressee Description J 83 1O-May-67 H J FICHT DCASR & DISBURSING OFFICE BOSTON Acceptance for 5451 gallons of herbicide dated May 10, 1967. Exhibit #P0618 PIN # Date Author Addressee Description J 74 1O-May-67 H J FICHT DCASR & DISBURSING OFFICE BOSTON Acceptance for 5451 gallons of herbicide, dated May 10, 1967. Exhibit #P0621 PIN # Date Author Addressee Description J 929 17-May-67 GEORGE F COLLINS FAIRCLOUGH & UNIROYAL CHEM DIV UNIROYAL INC Contract for 50,000 gallons herbicide to be shipped by June 30, 1967. Contract is dated May 17, 1967 and is a negotiated contract. Exhibit #P0624 PIN # Date Author Addressee Description J 82 23-May-67 M JEFFERY DCASR Sc DISBURSING OFFICE BOSTON Acceptance of 5451 gallons of herbicide, dated May 23, 1967. Exhibit #P0625 IV. A. 244 15694 PIN # Date Author Addressee Description C056178 11-Aug-70 H A THOMSON GORMAN, A & MURPHY, TOM CHUNG, Y Memorandum dated August 11, 1970 from H. A. Thomson to Gorman, Murphy, and Chung relating to the problems of identifying dioxin in chlorophenols through gas chromotography. Attempts to identify peaks. Notes results of cooperative tests and concludes that "our" material has about 10 ppm. Exhibit #P0997 PIN # Date Author Addressee Description 061319 18-Mar-71 A H GORMAN GRD & WJH PCT & FMH HAT & OTHERS Confidential internal memorandum dated March 18, 1971 from A. H. Gorman to a large circulation list entitled "2,4,5-T Uniroyal Position." The memorandum outlines Uniroyal's history with 2,4,5-T and the "Agent Orange" Program, highlight-- lighting defensive factors, the 1 ppm standard, assurances from suppliers, and inability to control field applications. Exhibit #P0998 PIN # Date Author Addressee Description C 60801 19-Mar-71 A H GORMAN PCT & GRD WEH & FMH HAT & OTHERS Internal Memorandum dated March 19, 1971 from A.H. Gorman to a wide variety of persons forwarding material on phenoxy herbicides and suggesting how calls about health problems should be handled. IV. A. 250 1 PIN # Date Author Addressee Description J 4715 23-May-67 R JEFFERY DCASR & DISBURSING OFFICE BOSTON Acceptance of 7413 gallons of herbicide, dated May 23, 1967. Exhibit #P0673 PIN # Date Author Addressee Description 605 29-Sep-67 SIEGAL IND TSTG LABS THOMPSON CHEM Eighty-three separate and dated reports showing the moisture content of samples of Thompson Chemical batches. Exhibit #P0693 PIN # Date Author Addressee Description THOMPSON-7 08-Nov-67 INTER OFFICE MEMOTHOMPSON CHEM InterofficeMemo110867 involving discussions w/ Kolker of Montrochem & again demonstrating the involvement of the Thompson Chemical people in the Thompson-Sterns-Rogers project & the knowledge concerning how the 2,4,5-T is manufactured, the problems, etc. Exhibit #P0722 PIN # Date Author Addressee Description THOMPSON-9 15-Jan-68 D W NORBERG 1 page report dated January 15, 1968 by D. W. Norberg of Stearns-Rogers entitled "Engineering Status Report". Exhibit #P0723 PIN # Date THOMPSON- 16-Jan-68 IV. A. 245 Author Addressee Description UNKNOWN Minutes of meeting concerning Thompson-Stearn-Rogers project, including Thompson & Buckley of Thompson Chemical dated 01-16,17,18 &19 showing total involvement of Thompson Chemical people, particularly Bill Thompson & M.S. Buckley, with respect to knowledge of 2,4,5-T, its manufacturing process, hazards, etc. Exhibit #P0725 PIN # Date Author Addressee Description 0000 22-Jan-68 MONTROCHEM PROCESS MEETING 01-22-68 Memo "Process Meeting w / Montrochem Consultants showing Thompson & Buckley of Thompson Chemical & Norberg & Angell of Stearns-Rogers & Bill Boyer present. Shows total involvement & knowledge of Buckley & Thompson in direct contravention to Thompson's sworn testimony. Plaintiff's position that this demonstrates Thompson's testimony has no credibility, in addition to establishing knowledge of Thompson Chem. concerning product, its contaminant, dioxin & potential health hazards & risks. Exhibit #P0735 PIN # Date Author Addressee Description THOMPSON-6 05-Feb-68 DEV CORP MONTROCHEM STEARNS-ROGERS CORP. 02-05-68 Expense Statement of Montrochem submitted by Montrochem to Stearns Rogers, showing Messrs. Colker & Burton of Montrochem or Stearns met with Messrs. Angell & Buckley on 12-27-67 concerning "review design plans for Weldon Springs proj ect. Exhibit #P0743 PIN # JUS0011 -a ^ (P*O ^ loboM IV. A. 246 Date Author Addressee Description 23-Feb-68 UNKNOWN UNKNOWN Purchase description for Herbicide Orange (Not a Mil-Spec) dated 2February 23, 1968. Exhibit #P0746 PIN # Date Author Addressee Description THOMPSON-10 26-Feb-68 JOHN BURTON DONALD NORBERG & M. BUCKLEY C.KOLKER Letter from John Burton, consulting chemical engineer to Donald Norberg of Stearns-Rogers corporation, attaching a memorandum concerning 2,4,5-T process description; this letter shows carbon copy to Mr. Buckley of Thompson Chemical. Exhibit #P0760 PIN # Date Author Addressee Description JUS0012 11-Apr-68 UNKNOWN UNKNOWN Purchase description for Orange II. Exhibit #P0772 PIN # Date Author Addressee Description UNKNOWN 24-May-68 W A FENNER THOMPSON Contract dated May 24, 1968 signed by W. A. Feener for the government and Thompson Chemical Company for herbicide. Exhibit #P0781 PIN # Date Author Addressee C 77065 22-Jun-68 F M HAGER RMN & GPD JCRW & KGP WME & CDMCC < r; ;Q 1^ IV. A. 247 I Description Minutes of Development Committee Meeting of June 22, 1968 1968 of Uniroyal (1966) Ltd., Chemical Division Elmira, Ontario Development Department, prepared by F. M. Hager. Reports that vapor-phase oxidation of 2,4-D has not been successful to date and promises continuing work. Identifies direct production of 2,4-D and 2,4,5-T as a "Top Priority" project. Exhibit #P0817 PIN # Date Author Addressee Description THOMPSON-13 26-Nov-68 HOWARD J BUCHHOLTZ Memo of conference concerning Weldon Springs chemical plant dated 11-26-68, showing Thompson & Buckley. Exhibit #P0823 PIN # Date Author Addressee Description THOMPSON-14 19-Dec-68 M S BUCKLEY DEPT. OF ARMY & J.N. MC LAGAN LARRY BECON Letter on Stearns-Rogers stationery dated December 19, 1968, signed by M. S. Buckley of Thompson-Stearns-Rogers concerning manufacture of 2,4,5-T and again showing total involvement of Thompson Chemical. Exhibit #P0840 PIN # Date Author Addressee Description THOMPSON-14 07-Feb-69 R L JR ANDERSON Memorandum dated Feb. 7, 1969 entitled "Minutes of Meeting concerning termination of DA CONTRACT... WELDON SPRINGS CHEMICAL PLANT..." This memorandum discusses termination of Weldon Springs project and again shows Thompson Chemical's involvement. IV. A. 248 Exhibit #P1012 PIN # Date Author Addressee Description JUS0007 16-Aug-71 R STAHL TATEM & KELLY AFB Analysis by Dow of Gulfport batches for dioxin. Handwritten onto the analysis, which is dated August 16, 1971, is an identification of the origin of the batches tested. Exhibit #P1106 PIN # Date Author Addressee Description THOMPSON-5 16-Sep-83 CORP STEARNS ROGER MONTROCHEM & DEVELOPMENT CORP. Purchase order dated 09-16-83 under heading Stearns Rogers Corp. to Montrochem Dev. Corp. concerning "Thompson-Stearns-Rogers Project" & generally showing total involvement of Thompson Chemical in the Stearns-Rogers project. IV. A. 251 Exhibit #P1134 PIN # Date Author Addressee 5870-4 01-Jan-01 UNKNOWN SUSKIND, M.D., WHEELER, E.P. R . R . & OETTEL, & WEGER,L.C. M.D . , H. Description Document describes meeting held at the Kettering Laboratory and Dr. Oettel sharing with representatives of Monsanto knowledge he possessed regarding Badische incident. Photographs of individuals with chloracne were exchanged by the parties. Exhibit #P1135 PIN # Date Author Addressee Description 256691-700 01-Jan-01 VERALD ROWE UNKNOWN HAZARDS IN HANDLING HERBICIDES Exhibit #P1136 PIN # Date Author Addressee Description 2183-95 01-Jan-01 UNKNOWN NONE GD BACKROUND INFORMATION RE: PROBLEMS AT MONSANTO Exhibit #P1137 PIN # Date Author Addressee Description 002183-23095 01-Jan-01 ROWE UNKNOWN Article written by Dr. Rowe entitled "Health Hazards Associated with Handling and Use of Herbicides." Exhibit #P1138 PIN # Date 006005 0 7 -0ct-01 IV. A. 252 , 15701 Author Addressee Description R EMMET KELLY ILLEGIBLE Letter from Kelly, M.D. of 2,4,5-T Manufacture; Nitro. re: Medical History contamination at Exhibit #P1139 PIN # Date Author Addressee Description 00000 10-0ct-10 KRISIK, H; JONES, L A Technique for Testing Acnegenic Potency in Rabbits, applied acnegen 2,3,7,8-TCP; written by Linn Jones and Helen Krizek. Exhibit #P1140 PIN # Date Author Addressee Description 00000 10-Oct-10 K H SCHULZ Occupational Chloracne Caused by Aromatic Cyclic Esthers written by K.H. Schulz. Exhibit #P1141 PIN # Date Author Addressee Description D0W21310-481 01-Aug-50 V K ROWE UNKNOWN TOXICITY OF 2,4-D AND 2,4,5-T Exhibit #P1142 PIN # Date Author Addressee Description DOW256691-00 01-Feb-52 V K ROWE MD NONE HLTH HAZDS ASS. W / HANDLNG AND USE OF HERB. Exhibit #P1143 IV. A. 253 PIN # Date Author Addressee Description D0W536347-54 01-Jan-54 V K ROWE ET AL NONE TOXLOG INF REGARDING D & T EFFTS ON LIVESTOCK Exhibit #P1144 PIN # Date Author Addressee Description DOW750691-93 09-Dec-55 VERALD ROWE J. W.BRITTON & L. SOUTHWICK K. C. BARRONS & J.E. JOHNSON W.W. ALLEN Letter discusses problems with reddon, with request for applications testing to agricultural and biochemical research attached dated 11/22/55. Routine toxicological study revealed that reddon produced a skin response in rabbits typical of those materials which produced acne -form dermatitis in man. It is stated that Reddon is not a satisfactory product for Dow to distribute to the General public. The responsible ingredient and the substitted indegredient have been deleted from the memo. Ten ingredients have been deleted from the memo. Exhibit #P1145 PIN # Date Author Addressee Description 278600-01 26-Oct-56 VERALD ROWE H.H. GAY Memo is claimed to be a summary of toxicological information that Dow has on Esteron 245. One of the active ingredients is stated to be 2,4,5-T. Claims that out side lab test on 200 humans revealed "... no primary irritation or any hypersensitivity." Letter states that "... we can only guess at what might appear in humans.", and refers to two other reports on toxicity of 2,4,5-T type herbicides and a study on "... Acute and Chronic Toxicity in Dogs." with respect to 2,4-D and 2,4,5-T. Page two, paragraph two lines 3,4,5 & 6 appear to have been deleted by IV. A. 254 someone. Exhibit #P1146 PIN # Date Author Addressee Description DOW568816-18 11-Feb-57 DR WEYLAND DOW Weyland's experience is that the chloracne exciting effect on impurities is formed if trichlorophenol sodium or other alkali salts is prepared from trichorophenol, purified and worked up further. Exhibit #P1147 PIN # Date Author Addressee 278591 21-Jun-57 VERALD ROWE R.O. FLETCHER H. H. GAY, MD && RD.. HL.. ACSOHNWNEORRTH Description Memo contains Rowe's comments regarding a claim that a pilot in Seattle had been exposed to esteron 44 that caused illness. Memo denies that a pilot spraying the product could be exposed to enough of the product to cause any illness and that no systemic toxicology from such activity could be obtained according to Dow's knowledge. Also, that it is difficult to believe that normal aerial application with due regard to safety could cause any illness. Exhibit #P1148 PIN # Date Author Addressee Description D0W278588 01-Oct-57 HAROLD M GAY MD UNINTELLIGIBLE & ROWE, V K BRYANT, C A LTR FRM GAY ESTRON 99 NOT THE CAUSE OF USERS RASH IV. A. 255 -<rr yb* ^ 1 siy' Exhibit #P1149 PIN # Date Author Addressee Description 00000 03-Feb-59 ALKALI DIAMOND BAK, EUGENE Signed employee patent agreement of Eugene Bak; Bak agreed to treat as confidential all information he acquired in the course of his employment with Diamond; included in this restriction was knowledge of all procedures, specifications and secret processes. Exhibit #P1150 PIN # Date Author Addressee Description 286577 22-Sep-59 E WIFFEN DR. MILLER & DR. MOONEY MACDONALD & ROWE WILSON Letter to Miller states that Dow of Canada does not presently have sufficient information regarding the possibility of detrimental effects on the human pancreas following exposure to Esteron brush killers. States letter will be forwarded to Biochemical group for discussion and that Rowe will contact Miller. Exhibit #P1151 PIN # Date Author Addressee 278576 18-Oct-59 HAROLD GORDON MILLER & MOONEY ROWE & WIFFEN Description Letter from Gordon to Miller states that Dow's biochemical research laboratories conducted a study regarding the effect of esteron on the human pancreas which revealed no relationship between exposure to the chemical and damage to the pancreas. Also according to their knowledge no evidence of intoxication would lead them to believe that the pancreas is subject to injury by Esteron exposure.. IV. A. 256 Exhibit #P1152 PIN # Date Author Addressee 278574 11-May-60 VERALD ROWE H.H. GAY & D.L. CONNER Description Letter refers to a request from Mr. Bain about information which could be used in defense of a claim that Esteron 44 had caused a cancerous growth on the neck. Rowe claims that Dow has no information from results of t evaluations or field studies which would indicate that Esteron 44 could produce cancerous growths and states that Esteron is not responsible. Exhibit #P1153 PIN # Date Author Addressee Description DS00008587 18-Oct-60 J A BORROR GUIDI, R.A. & SIEMONEIT, J.R. WEINER, H . S . Confidential Memo from Borror to Guidi. Borror mentioned Diamond's exchange of correspondence with Boehringer relative to the production of TCP. He also commented on severe liver damage that resulted from a plant explosion in Germany that had been producing TCP. Exhibit #P1154 PIN * Date Author Addressee Description DOW750814-27 01-Jun-61 KEN OLSEN DOW & MCINTYRE, H H PERKINS, R P & GAY.MD H H OTHERS Dow biochemical research laboratory's document entitled, "Results of Range Finding Toxicological Tests on Esteron 2,4,5-0.S." (Replacement for Present Formulations M-1257) IV. A. 257 iJ.rr C Exhibit #P1155 PIN # Date Author Addressee Description DOW382172 22-Jun-61 JOSEPH V KLAUDER ROWE, V.K. Letter from Klauder, M.D. to Rowe re: final result of rapcated insult patch test with 1 per cent aqueous solution of Kurosal SL; performed on 50 subjects; 3 times weekly 12 consecutive times; no cutaneous reaction; no evidence of primary irritant, fatiguing, or allergic reaction. Exhibit #P1156 PIN # Date Author Addressee Description DOW382169-71 20-Jul-62 V K ROWE Letter of report summarizing Toxicological Information Concerning KUROSAL SL and KUROSAL G by V.K. Rowe, letter attached from Rowe to Wiffen re: above. Exhibit #P1157 PIN # Date Author Addressee Description DS00008832-3 0 7 -Jan-63 R F LINDEMAN HILL, W.E. & GUIDI, R.A. ROSENFELD, M. & G00DL0E, W. KENNEDY, F.R. Memo from Lindemann to Hill re: TCP and T-Acid Impurities; Lindemann recites the findings relative to impurities found in Diamond's TCP and T-acid. Exhibit #P1158 PIN # Date Author Addressee DOW008172-4 05-Mar-63 C P O'HARE GORDON, DR.H.L. & ROWE, V.K. KRAMER, C.G. & SILVERSTEIN, L . G . HOLDER, B.B. & 5 OTHERS Description Letter from O'Hare to Gordon, M.D. re : C.j IV. A. 258 washing as a prophylactic measure to control folliculities produced in the rabbit ear by repeated applications of various concentrations of symmetical TCDD; Results: washing quite ineffective; delays the formation of folliculitis. Exhibit #P1159 PIN # Date Author Addressee Description DS00024442-9 28-Mar-63 KEY, M M; BIRMINGHAM, D J Dermatoses Investigation conducted by Donald J. Birmingham and Marcus M. Key; occupational health research; chloracne in production of 2,4,5-T in workers. Exhibit #P1160 PIN # Date Author Addressee Description DS03247 61-3 29-Mar-63 C E MINARIK FILES Memorandum for Record from Minarik re: Criteria for Selection of Defoliation and/or Vegetation Control Agents. Exhibit #P1161 PIN # Date Author Addressee Description DS1266-94 26-Apr-63 FRANK L BAUER Minutes of meeting on April 26, 1963 at Edgewood Arsenal to discuss and evaluate the toxicity of 2,4-D and 2,4,5-T compounds with particular emphasis on use of these materials in military operations as herbicides. Exhibit #P1162 PIN # Date Author DS00019520 1O-Jun-63 R A GUIDI 157 GS IV. A. 259 Addressee MCDURNEY, R. & BROWN, C.R. CORT, J.S. & KENNEDY, F.R. Description Interoffice correspondence from Guidi to McDurney re: Chloracne; Guidi advised that Kennedy would keep Dr. McBurney informed relative to his discussions with Mr. Bleiberg about the worker's medical reports. Exhibit #P1163 PIN * Date Author Addressee DS00018043-4 18-Jun-64 S B HONOUR GILES, C.W. Description Letter from Honour to Giles at Alexander & Alexander; Honour requested Giles to initiate settlement of the workers' claims without waiting for the outcome of the government's investigations which he felt would favor the workers. He also mentioned the increasing pressure of unsatisfied claimants on Quimor. Exhibit #P1164 PIN # Date Author Addressee Description DOW724316-23 01-Oct-64 HYMAS, T A; ROWE, V K "Summary of Toxicological Information on 2,4-D and 2,4,5-T Type Herbicides and an Evaluation of the Hazards to Livestock Associated with Their Use" by V.K. Rowe and T.A. Hymas; toxicological information on the use of 2,4-D and 2,4,5-T for use as control of undesirable vegetation. Exhibit #P1165 PIN # Date Author Addressee Description D0W129844-46 22-Feb-65 D E PLETCHER ' DOEDENS, J. D. Summary of meeting (VK Rowe present) to discuss knowledge of exciter components in f'" O i 1 0 ! w " IV. A. 260 Dow 2,4,5-trichlorophenol, potential hazards, possible effect on Dow image, legal implications, and possible quarantine (not considering economic impact). Exhibit #P1166 PIN # Date Author Addressee Description D0W170736 26-Feb-65 DAVID M GROTH UPTON, EDWIN T. Letter from Groth to Upton re: samples requested; results on own techniques used for separation. Exhibit #P1167 PIN # Date Author Addressee Description DS00012602-3 FC26OR-RMTaK, yE-NJ6N. 5EDY Interoffice memorandum from Kennedy to Cort re: Chromotograph Progress Report; Kennedy was keeping Cort, Manager of the Division, advised of the latest developments in Newark's dioxin detection and removal program. Exhibit #P1168 PIN # Date Author Addressee Description 21745-48 22-Jun-65 DNOOWNE Dow document describing the analytical method to determine 2,3,7,8 Tetrachlorodibenzo-p-Dioxin in 2,4,5-Trichloropheloxyacetic acid by gas-liquid chromatography bearing Monsanto Bate's number. Exhibit #P1169 PIN # Date Author J4061-4068 10-Aug-65 T EVANS IV. A. 261 ry, J Addressee Description UNKNOWN Paper explains the dioxin and Dow midland meeting. Document suggest that the problem should not be discussed outside the division at present and that Dow suggested that no 2,4,5-T products containing dioxin should be sold. Describes the effects of dioxin and different tests performed and the results. It is stated that Dow has developed a process to remove the dioxin by a treatment of the 2,4,5-T acid with benzene but would not disclose what the process was. Exhibit #P1170 PIN # Date Author Addressee Description 00000 0 1 -Jan-66 CARSTENS L A; ALLEN J R "Electron Microscopic Alterations in the Liver of Chickens Fed Toxic Fat" written by James R. Allen and Laurine A. Carstens. Exhibit #P1171 PIN # Date Author Addressee 74270-83 15-Aug-66 G M DOWNARD MONSANTO CO. & SIDO, ROBERT Description This document indicates that the USDA refused to register Monsanto's 2 ,4-D/2,4,5-T Butyl Ester Brush Killer. The document also contains numerous enclosures regarding the aforementioned matter. Exhibit #P1172 PIN # Date Author Addressee Description 74365-91 03-Nov-66 G ROBERT SIDO USDA Packet of documents regarding Monsanto's modified renewal application for the product known as 2,4,5-T Ester Brush Killer, filed with the USDA for the purpose of registering this product. IV. A. 262 Exhibit #P1173 PIN # Date Author Addressee Description JUS947-8 01-Jan-67 DALE UNINTELLIGBLE NONE Document entitled "Memorandum For Deputy Chief of Staff , systems & Logistics, USAF, Subject: Herbicide Orange". Exhibit #P1174 PIN # Date Author Addressee Description 21390-91 28-Mar-67 C H RUSSELL DOLIN, 0. E. & BALDERSON, PHIL CUTRIGHT, E. A. & DUNLAP, W. P. STEPHENS, J. A. Semichronic oral toxicity of 2,4-Dichlorophenoxyacetic Acid to rats prepared for Dow Biochemical Research Dept. Indicates while data on results of toxicologuical tests on 2,4,5-T acid is omitted from the document. Exhibit #P1175 PIN # Date Author Addressee Description DS00016934-5 05-Jul-67 C W CARTY CORT, J.S. Letter from Carty at Dept, of Array to Cort; Carty requested Diamond to review and comment on the enclosed copy of the proposed military specification, Agent Orange II and Orange III. He was looking for constructive suggestions that could be incorporated into the specifications. Exhibit #P1176 PIN # Date Author Addressee 00000 01-Sep-67 CARSTENS L A ALLEN J R IV. A. 263 Description "Light and Electron Microscopic Observations in Macaca Mulatta Monkeys Fed Toxic Fat" written by J.R. Allen and L.A. Carstens. Exhibit #P1177 PIN # Date Author Addressee DOW 278589 05-Oct-67 C BRYANT V.K. ROWE & DR. GAY Description Memo from Bryant to Rowe suggesting that Rowe answer inquiry from Mrs. Ernest Stahmer of Oklahoma. Rowe suggests in memo to Dr. H.H. Gay that Gay answer the letter of Mrs. Stahmer. Exhibit #P1178 PIN # Date Author Addressee Description 93-4 n-Oct-67 C H RUSSELL ZORCH, C P & CAYARD, D E DAVIS, A F & FISCHER, D R STEPHENS, J A Document in which Russell openly admits that he wrote the specifications for Agent Orange. Exhibit #P1179 PIN # Date Author Addressee 21492 03-Nov-67 R ATKINSON SPRINGGATE & KELLOGG DOLIN & CUTRIGHT RHODES & HOWELL Description Memo states natcp production step is limiting production of 2,4,5-T acid and suggests that purchasing outside natcp would allow for greater production of 2,4,5-T acid at the Nitro plant. A savings of $98,000.00 per year is predicted. D r-i 1 s 3 IV. A. 264 Exhibit #P1180 PIN # Date Author Addressee 21389 11-Oct-68 F HELMER R.A. ATKINSON & W.R. UDELL E.A. OUTRIGHT & O.E. DOLIN V.L. RHODES & J.C. STRUM Description Report on Na 2,4,5-T cake washing to improve color and residual TCP. Exhibit #P1181 PIN # Date Author Addressee Description 00000 16-NOV-68 G R HIGGINBOTHAM HUANG, ANITA & FIRESTONE, DAVID VERRETT, JACQUELINE & RESS, JOHN CAMPBELL, A.D. Story in "Nature" called Chemical and Toxicological Evaluations of Isolated and Synthetic Chloro Derivatives of Dibenzo-p-dioxin; written by Higginbotham Huang, Firestone, Verrett, Ress, Campbell. Exhibit #P1182 PIN # Date Author Addressee DS00012604-5 19-Dec-69 F R KENNEDY BALDESCHWEILER, J. & EISLER, MILTON Description Letter from Kennedy 2,4,5-T submitted to to Baldeschweiler re: Bionetics Corp. Exhibit #P1183 PIN # Date Author 148293-5 11-Mar-70 LAWRENCE FISHBEIN PHD Addressee Description FALK, DR HANS L Document indicates that members of the 2,4,5-T industry met with various governmental agencies and discussed "Chlorophenols and Chlorodibenzodioxins" Dr. Linn (Dow) indicated that no 14 IV. A. 265 teratological changes or lesions were observed when using T with a level of .5ppm. Dr Kolbye stated that even clean 2,4,5-T is a teratological hazard. Tests have shown that purified T as well as T with 4ppm caused a high rate of mortality . Exhibit #P1184 PIN # Date Author Addressee Description 74316-64 29-Jun-70 G ROBERT SIDO US DA Packet of documents regarding Monsanto's request for an amendment of a registration regarding the product known as 2 ,4-D/2,4,5-T Amine Brush Kill. Exhibit #P1185 PIN # Date Author Addressee 74480-29 10-Jul-70 G ROBERT SIDO ALFORD, HAROLD G & USDA Description This is a packet of documents regarding the USDA's suspension of the registration of the product known as 2,4,5-T Low Volitile Ester Brush Killer. Exhibit #P1186 PIN # Date Author Addressee 76737-843 23-Jul-70 PSAC BALDERSWIELER, J D & MACLEOD, COLIN M BRADY, NYLE & FARBER, EMMANUEL WILSON, JAMES G & OTHERS Description This document is the PSAC's draft report on 2,4,5-T. Exhibit #P1187 PIN # 7039-7040 IV. A. 266 5 Date Author Addressee 13-Nov-70 ROBERT MUELLER CHARLES ZORSCH & MONSANTO Description Document entitled, "Summary of Toxicological Information on 2,4-D and 2,4,5-T Type Herbicides and an Evaluation of the Hazards to Livestock Associated with Their Use." Exhibit #P1188 PIN # Date Author Addressee Description 74416-79 21-Dec-70 A E CONROY II MONSANTO CO. Packet of documents mailed by the EPA regarding Monsanto's labeling numerous products containing 2,4-D or 2,4,5-T. Exhibit #P1189 PIN # Date Author Addressee Description 00000 15-Jan-71 CHARLES ZORSCH GEORGIA PACIFIC & REX BLACK WERNER HARRIS Letter from the Medical Director at Dow which advises a user of Esteron 99 that the skin irritation is not related to the use of that product. Exhibit #P1190 PIN # Date Author Addressee Description 00000 01-Mar-71 SMITH POLAND A Health Survey of Workers in a 2,4-D and 2,4,5-T Plant with special attention to chloracne, porphyria cutanea tarda, and psychologic parameters; written by Poland, Smith, Metter, Possick. Exhibit #P1191 IV. A. 267 * JLO PIN # Date Author Addressee Description 74284-98 24-Feb-72 G ROBERT SIDO MON CO US DA Packet contains various documents regarding Monsanto's request of th USDA for a registration renewal of their product known as 2,4,5-T Isooctly Ester Tech Grde. Exhibit #P1192 PIN # Date Author Addressee Description 74392-03 01-Mar-72 ROBERT SIDO MON USDA Packet of documents regarding Monsanto's renewal registration of the product known as 2,4,5-T Butyl Ester Technical Grade. Exhibit #P1193 PIN # Date Author Addressee Description DS22629-32 20-Nov-72 J J LUKES LAVERGNE, E.A. & FISH, G.L. O 'LEARY, K.J. & IRANI, R.R. FILES Interoffice memorandum from Lukes to Lavergne re: Recovery of D&T from Agent Orange; cited the proposed progress for the recovery of saluble 2,4-D butyl esther and 2,4,5-T acid from Agent Orange. The potential advantages as well as the disadvantages of such a program were reviewed. Exhibit #P1194 PIN # Date Author Addressee DS00021570-1 23-Jan-73 A WHYTE GALLUP, W.A. & CRYBERG, R.L. JANZ, W.A. & LASCO, R.H. LAVERGNE, E.A. & FILES Description Memo from Whyte to Gallup re: Progress Report, January, 1973; Progress report on the dioxin removal from Agent Orange. 15s-?-<: CX IV. A. 268 Exhibit #P1195 PIN # Date Author Addressee Description 00000 01-Sep-73 DAVID FIRESTONE "Etiology of Chicken Edema Disease" written by David Firestone. Exhibit #P1196 PIN # Date Author Addressee Description 00000 01-Sep-73 STEHL R H CRUMMETT W B "Determination of Chlorinated Dibenzo-p-dioxins and Dibenzo-p-furans in Various Materials" written by W.B. Crummett and R.H. Stehl. Exhibit #P1197 PIN # Date Author Addressee Description 00000 01 -Sep-73 BRADY T P LANGER H G BRIGGS, P.R. "Formation of Dibenzodioxins and Other Condensation Products from Chlorinated Phenols and Derivatives" written by H.G. Langer, T.P. Brady, and P.R. Briggs. Exhibit #P1198 PIN # Date Author Addressee DOW5593-95 08-Jul-74 DD MCCOLLISTER M. LENG & W. CRUMMETT J. DAVIDSON & P. GEHRING GETZENDANER & JENSEN, ET AL Description FIRST MEMO IS FROM MCCOLLISTER TO LENG DIRECTING THAT LENG LETTER OF 7/3/74 IS NOT TO BE SENT OUT UNTIL IT IS KNOWN WHAT EPA'S POLICY IS GOING TO BE WITH RESPECT TO IV. A. 269 HANDLING THE RESIDUE TOLERANCE PETITION. SECOND MEMO FROM LENG TO MCCOLLISTER AGREES TO HOLD THE LETTER BUT QUESTIONS WHETHER DOW IS OBLIGATED TO SUBMIT PERTINENT INFORMATION TO RESIDUES AND TOXICOLOGY. SAYS NOT INFORMING GOVERNMENT ABOUT TCDD IN 2,4,5-T IS WHAT GOT THEM IN TROUBLE IN THE FIRST PLACE & THAT WITHHOLDING INFORMATION ONLY MAKES THE GOVERNMENT THINK DOW IS TRYING TO HIDE SOMETHING FROM THEM. LETTER STATES THAT DISMISS OF PUBLIC HEARING BY EPA DOES NOT MEAN THERE ARE NO PROBLEMS AND REQUESTS ADDITIONAL DATA TO PREPARE AMENDMENT OF 2,4,5-T REPORT AND NOTES THEY HAVE NO TOLERANCES FOR 2,4,5-T . Exhibit #P1199 PIN # Date Author Addressee Description 294508 11-Sep-74 RENATE D KIMBROUGH DIRECTOR & CLINICAL CHEMISTRY DIVISION Memorandum from Kimbrough to Director of Clinical Chemistry Division re: Microscopic Examination of Livers and Ear Lobes of Rabbits; cc: Dr. Meath, Dr. Carter, Dr. Falk, Mr. Barthel, Dr. Liddle, Dr. Clinn. Exhibit #P1200 PIN # Date Author Addressee Description 294510 06-Nov-74 JOHN H RICHARDSON CARTER, COLEMAN D. & HEATH BARTHEL Letter from Richardson to Carter re: Animal Studies with 2,3,7,8-TCDD. Exhibit #P1201 PIN # Date Author Addressee Description 000000 01-Apr-79 EPA DRAFT EPA This document is the preliminary draft of an EPA study entitled, "Dioxins: Sources, Transport, Exposure, and Control." 15 1X 9^ IV. A. 270 Exhibit #P1202 PIN # Date Author Addressee Description JUS 312 94-6 28-Aug-80 FRANK S. SERDY EPA - R.J. TAYLOR Letter to EPA from Monsanto requesting EPA cancellation of all 2,4-D registrations held by Monsanto, removal of Monsanto from list of data submitters and producer of this chemical. Exhibit #P1203 PIN # Date Author Addressee Description JUS 312 88 03-Dec-80 FERIAL S BISHOP MONSANTO COMPANY Letter from U.S. Environmental Protection Agency regarding notice sent on September 23, 1980, notifying of intent to cancel registrations of certain EPA products including certain Monsanto 2,4-D, 2,4,5-T products. Exhibit #P1204 PIN # Date Author Addressee Description DS1266-94 26-Apr-83 FRANK L BAUER Minutes of meeting on April 26, 1963 at Edgewood Arsenal to discuss and evaluate the toxicity of 2,4-D and 2,4,5-T compounds with particular emphasis on use of these materials in military operations as herbicides. Exhibit #P1205 PIN # Date Author Addressee DS00003810-1 27-Jun-83 E L CHANDLER PIERSON, P.G. & LINDEMANN, R.F. 15720 IV. A. 271 Description KENNEDY, F.R. Letter from Chandler to Pierson. Chandler submitted a recommendation for the government specifications for Agent Orange relative to the free acid. Exhibit #P1206 PIN # Date Author Addressee Description 001564 14-Sep-65 Agricultural Research - St. Louis Take, E F (Nitro) & Dunlap,W P Stephens,J A & Sharp,D B Analysis of four autoclave batches indicates that, although it was previously known (April, 1965) that the concentration of TDD in the TCP is approximately equal to the concentration of TDD in T-acid produced from the TCP, during April 1965 it was observed that production of TDD rose to an all-time high, and it has remained much higher than the previous norm. IV. A. 272 15121 IV. B. Plaintiffs respectfully submit the following initial list of documents in response to paragraph IV. (E) (2) of Magistrate's Pretrial Order No. 17. Plaintiffs reserve the right to amend this list in conformity with the schedule for filing the amendment to this Pretrial Order and the final form. Plaintiffs refer all counsel in connection with this list to all Rule 26 (B)(4)(a)(1) statements and summaries together with attachments thereto which have been filed previously some of which will be filed in amended form in conformity with the Magistrate's ruling in those regards. The documents are, as follows: Exhibit #P0002 PIN # Date Author Addressee Description 19 B P MCNAMARA McNamara, B.P., Summary of toxicity Data of Phenoxyacitates. Exhibit #P0003 PIN # Date Author Addressee Description 48 G LAWTON Lawton, G. "E.300 Chloracne Study." IV. B. 1 15*? 2 2 Exhibit #P0004 PIN # Date Author Addressee Description 69-80 VARIOUS VARIOUS Sixth, Fourteenth, Second, Seventh, Ninth, Tenth Eleventh, Twelfth, Thirteenth, Fifteenth, Sixteenth, Seventeenth, Quarterly Progress Reports to National Cancer Institute, Program of Carcinogenesis Studies, from Bionetics Research Laboratories, Inc. Exhibit #P0005 PIN # Date Author Addressee Description 56 D W GOLDSTEIN Goldstein, D.W. ''Chloracne from Marketing Herbicide." Exhibit #P0006 PIN # Date Author Addressee Description 56 LOUIS SCHWARTZ G.O. NELSON Letter from Louis Schwartz to G.O. Nelson dated May 11, 1949. .... **:=4 'D i IV. B. 2 Exhibit #P0007 PIN # Date Author Addressee Description 88 UNKNOWN Unlisted Drugs list. Exhibit #P0008 PIN # Date Author Addressee Description 89 BENJAMIN WITTEN Title page, pages 202-205 and page 308 of Edgewood Arsenal Technical Report 4210 "The Search for Toxic Chemical Agents: by Benjamin Witten. Exhibit #P0040 PIN # Date Author Addressee Description 00 01-Jan-01 REVIEW V A PUBLISHED & BIBLIOGRAPHY DIOXIN Article entitled "Veteran's Administration review of literature on herbicides, including phenoxy herbicides and associated dioxins," two volumes which comprise a fairly comprehensive search of the i *79 s IV. B. 3 literature regarding herbicides which may. be offered in whole or in part, at least be certain articles cited therein may be used at time of trial. Exhibit #P0043 PIN # Date Author Addressee Description 47 01-Jan-43 L SCHWARTZ Schwartz, L . , "An Outbreak of Halowax Acne ('Cable Rash') Among Electricians," 122 JAMA 158-61 (1943). Exhibit #P0049 PIN # Date Author Addressee Description 58 16-Aug-49 LOUIS SCHWARTZ G.O. NELSON Letter from Louis Schwartz to G.O. Nelson dated August 16, 1949. Exhibit #P0050 PIN # Date Author 00 05-Dec-49 WILLIAM ASHE IV. B. 4 15725 Addressee SUSKIND, RAYMOND & REPORT ON MONSANTO Description This report is dated December 5, 1949 from Dr. Wm. Ashe and Dr. Raymond Suskind (Dermatologist) to Monsanto Management, and the Kettering Laboratory in Cincinnati, Ohio and demonstrates acute neurotoxic, systemic, and dermatological disorders to workers exposed to TCDD also shows immune disregulations following exposure. Exhibit #P0051 PIN # Date Author Addressee Description 00 19-Dec-49 G D NELSON ASHE, WM MD Letter criticizes Ashe's initial reporting of the serious injuries of Monsanto workers at 2,4,5-T Plant following incident in autoclave. Exhibit #P0052 PIN # Date Author Addressee Description 00 27-Dec-49 WILLIAM ASHE NELSON, G D Letter regarding Ashe's response to the company's (Monsanto) criticism of his findings RE Workers seriously injured at IV. B. 5 *2 K 0 X \J a & ^ the 2,4,5 -T Plant in Nitro, West Virginia in 1949. Exhibit #P0064 PIN # Date Author Addressee Description 00 01-Jan-53 WILLIAM ASHE SUSKIND This report dated 1953 summarizes the findings of Dr. William Ashe and Dr. Raymond Suskind on the 1949 incident at Nitro Plant in West Virginia; both Doctors are listed at the Kettering Laboratory in the Department of Preventive Medicine and Industrial Health, College of Medicine, University of Cincinnati, Cincinnati, Ohio. Exhibit *P0073 PIN # Date Author Addressee Description 00 06-Jun-55 WILLIAM ASHE SUSKIN, RAYMOND This document clearly reflects in 1955 Monsanto's characterization of 2,4,5-T and its dioxins as chemically intoxicating, characterized by acneform skin lesions, hepatitis, disturbed lipid metabolish , peripheral neuropathy, and probably mild central nervous system involvement. 1 IV. B. 6 Exhibit #P0085 PIN # Date Author 63 01-Jan-56 P DUGOIS Addressee COLOMB, H. from LA Description Dugois, P. and Colomb, H . , "Chloracne 2,4,5-Trichlorophenol,"63 BULLETIN DE SOCIETE FRANAISE 262-63 (1956) (translation). Exhibit P0095 PIN # Date Author 00 01-Jan-57 J KIMMIG Addressee SCHULTZ, K H 115:540-546 Description PUBLISHED IN DERMATOLOGICA VOL. (1 957) Exhibit #P0104 PIN # Date 01 01-Oct-57 IV. B. 7 \ Akne English Caused Author VON J KIMMIG Addressee SCHULZ, K.H. Description Kimmig, J . , Schulz, K.H., "Berufiche (sog. Chlorakne) durch chlorierte aromatische zyklische ther", and Translation, "Occupational Chloracne by Aromatic Cyclic Ethers," 115 DERMATOLOGICA 540-46 (1957). Exhibit #P0117 PIN # Date Author Addressee 11 01-Jan-59 M TOMITA UEDA, S. & NARISADA, M. XXVII. Description Tomita, M . , Ueda, S., Narisada, M . , "Studies on the Dibenzo-ppdioxin (Diphenylene Dioxide) Derivatives Synthesis of Polyhalodiobenzo-p-dioxin" (1 959) . Exhibit #P0129 PIN # Date 21 05-Oct-59 IV. B. 8 15 7 2 ^ Author F HOFFMANN Addressee Description Extract of Report on Trip to Europe, Hoffmann, F., October 5, 1959. Exhibit #P0130 PIN # Date Author 21 05-Oct-59 F HOFFMANN Addressee Description Report on Trip to Europe, Hoffmann, F. October 5, 1959. Exhibit #P0151 PIN # Date Author 00 0 1 -Jan-61 ET AL BAUER Addressee Description Article by BAUER published in "FUER GEWERBEPATHOLOGY UN GEWERBEHYGIN" VOL. 18:538-555. Exhibit #P0152 PIN # 36 IV. B. 9 15730 Chick Date Author 01 -Jan-61 A YARTZOFF Addressee Description Yartzoff, A., et al., "Studies of the Edema Factor, II. Isolation of a Toxic Substance" (1961). Exhibit #P0162 PIN # Date Author 25 08-Mar-62 J W BROWN Addressee 1962). Description Brown, J. W . , "Preliminary Report of Vegetational Spray Tests" (March 8, Exhibit #P0175 PIN # Date Author 02 2 6 -Jun-62 E L JONES MD Addressee HELEN KRIZEK, PH.D. Description Jones, E.L., Krizek, H . , "A Technic for Testing Acnegenic Potency in Rabbits, Applied to the Potent Acnegen 2,3,7,8-Tetrachlorodiobenzo-p-Dioxin," 39 15731 IV. B. 10 (1 962). J. INVESTIGATIVE DERMATOLOGY 511-17 Exhibit #P0180 PIN # Date Author 31 04-Aug-62 HAROLD BROWN Addressee SECY OF DEFENSE 1962. Description Memorandum from Harold Brown to the Secretary of Defense dated August 4, Army Exhibit #P0181 PIN # Date Author 90 07-Sep-62 ROBERT J GOODLOW Addressee ARMY CH.RES.DEV.LAB Description September 7, 1962 memo from Robert J. Goodlow to Commanding Officer, U.S. Chemical Research and Development Laboratories. Exhibit #P0182 IV. B. 11 15732 PIN # Date Author 91 28-Sep-62 B WITTEN Addressee ARMY CH.RES.DEV.LAB Description September 28, 1962 memo from B. Witten to Commanding Officer, U.S. Army Chemical Research and Development laboratories. Exhibit P0183 PIN # Date Author 92 04-Oct-62 D W FALCONER Addressee Description October 4, 1962 memo from D.W. Falconer to Commanding Officer, U.S. Army Chemical Research and Development Laboratories. Army Exhibit #P0184 PIN # Date Author 93 15-Oct-62 ROBERT J GOODLOW Addressee ARMY CH.RES.DEV.LAB Description October 15, 1962 memo from Robert J. Goodlow to Commanding Officer, U.S. IV. B. 12 Chemical Research and Development laboratories. Exhibit #P0187 PIN # Date Author 49 28-Nov-62 DAVIS W GOLDSTEIN Addressee KEY, MARCUS M Marcus December Description Letters from Davis W. Goldstein to M. Key dated November 28, 1962, 17, 1962, and April 5, 1963. Army Exhibit #P0188 PIN # Date Author 94 29-Nov-62 ROBERT J GOODLOW Addressee ARMY CH.RES.DEV.LAB Description November 29, 1962 memo from Robert J. Goodlow to Commanding Officer, U.S. Chemical Research and Development Laboratories. IV. b . 13 15734 Exhibit #P0189 PIN # Date Author Addressee 27 01-Dec-62 JA COATES POLLACK, H & SHARPE, L ROBERT PHELPS "The Needs" Description Coates, J., Sharpe, L . , Pollack, H . , Present Status of Chemical Control of Vegetation in Relation to Military (December, 1962) including distribution letter by Robert Phelps. Exhibit #P0190 PIN # Date Author 95 1O-Dec-62 B WITTEN Addressee ARMY CH.RES.DEV.LAB Description December 10, 1962 memo from B. Witten to Commanding Officer, U.S. Army Chemical Research and Development laboratories. Exhibit #P0191 PIN # Date Author 28 11-Dec-62 NONE HEASTON IV. B. 14 15735 Vegetation" Addressee Description Heaston, "Chemical Control of (December 11, 1962). Exhibit #P0209 PIN # Date Author 50 27-Mar-63 MARCUS M KEY Addressee GOLDSTEIN, DAVIS W. Key 1963. Description Letter with attachments from Marcus M. to Davis W. Goldstein dated March 27, Exhibit #P0210 PIN # Date Author 44 28-Mar-63 D J BIRMINGHAM Addressee KEY, M.M. "Dermatoses Description Birmingham, D.J., Key, M . M . , Investigation" (March 28, 1963). IV. B. 15 K .O *1 s I Q Exhibit #P0214 PIN .# Date Author 51 19-Apr-63 MARCUS M KEY Addressee GOLDSTEIN, DAVIS W. Description Letter from Marcus M. Key to Davis W. Goldstein dated April 19, 1963. Exhibit #P0217 PIN # Date Author 65 22-Apr-63 MARCUS M KEY Addressee MCCRANEY, H.C. McCraney Description Letter from Marcus M. Key to H.C. dated August 22, 1963. Exhibit #P0218 PIN # Date Author 52 25-Apr-63 NONE NONE Addressee U.S. DEPT OF LABOR dated Description Letter to U.S. Department of Labor April 25, 1963. IV. B. 16 15737 Exhibit #P0219 PIN # Date Author 10 26-Apr-63 COL FRANK L BAUER Addressee and 2,4,5-T 26, Description Minutes of a Meeting held to Discuss Evaluate the Toxicity of 2,4-D and compounds, with appendices, dated April 1963. Exhibit #P0224 PIN # Date Author Addressee 15 09-May-63 NONE AGENDA PSAC & THE PENTAGON PSAC, 1963 ADVISORY Description Tentative Agenda for Meeting of the The Pentagon, Washington, D.C., May 9, with attachments. Attachments include BRIEFING TO PRESIDENT'S SCIENTIFIC COMMITTEE 9 MAY 1963 BY CBR AGENCY PERSONNEL ON POSSIBLE HEALTH HAZARD OF IV. B. 17 DEFOLIATION PHENOXYACETATES AS RELATED TO OPERATIONS IN VIETNAM "Use Exhibit #P0225 PIN # Date Author 04 15-May-63 SCI ADVIS COMM PRESIDENTS Addressee Description President's Science Advisory Committee of Pesticides" (May 15, 1963). Exhibit #P0228 PIN # Date Author 53 27-May-63 NONE NONE Addressee KEY, MARCUS M. 1963. Description Letter to Marcus M. Key dated May 27, Exhibit #P0243 PIN # Date 23 29-JuI-63 IV. B. 18 iL- ivO July Author J C WARD Addressee Description Meeting of Subcommittee on Herbicides, 29, 1963 by Ward, J.C. Exhibit #P0244 PIN # Date Author 24 30-Jul-63 R G MCCALL Addressee ALVELLINO, J.D. McCall, Description Memo for Record, July 30, 1963 from R.G. and Avellino, J.D. Exhibit #P0246 PIN # Date Author 64 09-Aug-63 H C MCCRANEY Addressee MARCUS M. KEY Description Letter from H.C. McCraney to Marcus M. Key dated August 9, 1963. IV. B. 19 .57 Exhibit #P0251 PIN # Date Author 26 1O-Oct-63 P OLENCHUCK Addressee Description Olenchuck, P. "Evaluation of Herbicide Operation in the Republic of Vietnam" (October 10, 1963). 1980 Exhibit #P0261 PIN # Date Author 00 01-Jan-64 ARTHUR W GALSTON Addressee Description Book published by Dr. Galston on plant physiology, Prentice-Hall, 1st edition, 1961; 2d edition 1964, 3rd edition, (with P.J. Davies and R.L. Satter). Exhibit #P0262 PIN # Date Author 61 01-Jan-64 NONE NONE Addressee LETTER TO EDITOR Description Letter to the editor "New Weed Killers Produce Chloracne," 189 JAMA 66-67 15741 IV. B. 20 (1964). Exhibit #P0296 PIN # Date Author 85 28-May-64 KENNETH KOPPLE Addressee GRANITO, CHARLES Description May 28, 1964 letter from Kenneth Kopple to Charles Granito. Exhibit #P0298 PIN # Date Author Addressee 03 0 1 -Jun-64 JACOB BLEIBERG MD MARVEN WALLEN, MD & ROGER BRODKIN, MD I.R. APPLEBAUM, MD Description Bleiberg, J . , Wallen, M., Brodkin, R . , Applebaum, I.L., "Industrially Acquired Porphyria," 89 ARCHIVES OF DERMATOLOGY 793-97 (1964). Exhibit #P0310 PIN # Date 86 18-Jul-64 IV. B. 21 Author GERHARD CLOSS Addressee GRANITO, CHARLES Description July 18, 1964 letter from Gerhard Closs to Charles Granito. Exhibit #P0311 PIN # Date Author 87 21-Jul-64 CHARLES GRANITO Addressee CLOSS, GERHARD Granito Description July 21, 1964 letter form Charles to Gerhard Closs. Exhibit #P0312 PIN # Date Author 45 24-Jul-64 D H GROTH Addressee Various 1964). Description Groth, D.H., "Microscopic Changes in Rabbits Secondary to Application of Pesticides to their Ears" (July 24, IV. B. 22 15743 Exhibit #P0335 PIN # Date Author 54 03-Dec-64 DAVID H GROTH Addressee UPTON, E.T. Upton 26, Description Letters from David H. Groth to E.T. dated December 3, 1964, and February 1965. Exhibit #P0340 PIN # Date Author 55 11-Dec-64 EDWIN T UPTON Addressee GROTH, DAVID H. 14, 1965. Description Letters from Edwin T. Upton to David H. Groth dated December 11, 1964, January 1965, February 17, 1965 and June 2, Exhibit #P0353 PIN # Date Author 46 12-Jan-65 D H GROTH IV. B. 23 15744 Acid Addressee Description Groth, D.H.f Project Development and Approval "Identification of the Toxic Factor in 2,4,5-trichlorophenoxyacetic (2,4,5-T)" (January 12, 1965). Exhibit #P0397 PIN # Date Author 73255 17-Mar-65 EMMET KELLY Addressee STEPHENS, JOHN to initialed Description toxic experienced." caution dioxin This letter was passed around monsanto, Dr. Paul Hoffman, and others as on letter, and shows knowledge of TCDD being by Dow and Monsanto the "most compound they (Dow) has ever Instructions to lab to use extreme in handling, since even trace amounts 200ppb have caused cholacne in rabbits. This further shows they could detect in the parts per billion range in 1965. IV. B. 24 1 et Exhibit #P0474 PIN # Date Author 59 0 1 -Jan-66 M M KEY Addressee BIRMINGHAM, D.J. "Occupational Description Key, M.M . , Birmingham, D.J., Chloracne", INTERNATIONAL CONGRESS ON OCCUPATIONAL HEALTH 752-55 (1966). Exhibit #P0475 PIN t Date Author 62 0 1 -Jan-66 D J BIRMINGHAM Addressee Occupational 639-43 Description Birmingham, D.J., "Preventable Dermatoses, "12 ARCH ENVIRON HEALTH (1 966) . Exhibit #P0556 PIN # Date Author 00 0 1 -Jan-67 J R ALLEN Addressee IV. B. 25 CARSTENS, L A 15746 Microscope Monkeys Vet. Description Paper entitled "Light Electron Investigations in Macaca Mulatta Fed Toxic Fat." American Journal of Res. 28: 1513-1526. Exhibit #P0557 PIN # Date Author 33 01-Jan-67 NONE NONE Addressee Description Portion of 1967 CHECO Report. Exhibit #P0590 PIN # Date Author 22 24-Feb-67 A P BEUTEL Addressee HEBBELER, JAMES W Description Letter to James W. Hebbeler from A.P. Beutel dated February 24, 1967. IV. B. 26 K yj A 1 Exhibit #P0627 PIN # Date Author 82 0 1 -Jun-67 NONE NONE Addressee SOP Appendices Description Edgewood Arsenal Research Laboratories NO 70-3 dated June 1, 1967, and A-H. hand Exhibit #P0632 PIN # Date Author 32 25-Jun-67 NONE NONE Addressee Description Portion of the DI7AF Report on Ranch Operations, June 25, 1967. Exhibit #P0672 PIN # Date Author Addressee 20 26-Sep-67 A P BEUTEL FREDERICKS & ANDERSON, ANDREW W SHEAD, C.G. & KRATZ, W. J. IV. B. 27 -jj ^n Q" J. September Description Letters to Fredericks with attachement, Andres W. Anderson, C. G. Shead and W. Kratz from A. P. Beutel, dated 26, 1967. Exhibit #P0674 PIN # Date Author 09 0 1 -Oct-67 W L ZIELINSKI Addressee FISHBEIN, L. 2,4,5-T AGR. Description Zielinski, W.L., Fishbein, L. "Gas Chromatographic Measurement of Disappearance Rates of 2,4-D and Acids and 2,4-D Esters in Mice, "15 J. FOOD CHEM. 841-44 (1967). Exhibit #P0675 PIN # Date Author 17 01-Oct-67 R BRETTS Addressee DENTON, F. Description Bretts R. and Denton F . , "An Evaluation of Chemical Crop Destruction in Vietnam," IV. B. 28 JL<u> a October, 1967 Exhibit #P0687 PIN # Date Author 18 30-Oct-67 JAMES A HEBBLER Addressee G.L. QUINN G.L. Reports" Description Memorandum from James A. Hebbeler to Quinn "Comments on Rand Herbicide October 30, 1967). Exhibit #P0705 PIN # Date Author 34 15-Dec-67 LT COL SHADE Addressee Description Handwritten note of telephone call from Lt. Col. Shade dated December 15, 1967. Exhibit #P0714 PIN # Date 37 01-Jan-68 IV. B. 29 15750 Author ET AL G R Addressee Description Preliminary draft and final version of Higginbotham, G.R., et al., "Chemical and Toxicological Evaluations of Isolated and Synthetic Chloro Derivatives of Dibenzo-p-dioxin, "222 NATURE 702-03 (1968) . Exhibit #P0789 PIN # Date Author Addressee PB-223159 0 1 - A u g -68 RESEARCH LABS BIONETICS US DEPT OF COMMERCE & FOR NCI Mutagenic Research Information Description Volume I entitled "Evaluation of Carcinogenic, Tera-Togenic, and Activities of Selected Pesticides and Industrial Chemicals, Bionetics Labs, Inc. Prepared for National Cancer Institute, And Under The Department of Commerce, National Technical Service; Volume I evaluates the carcinogenic risks to animals and man. IV. B. 30 1 Exhibit #P0790 PIN # Date Author Addressee PB-223160 01-Aug-68 RESEARCH LABS BIONETICS VOLUME II & FOR NCI in Labs, Vietnam. Description Volume II entitled "Teratogenic Study Mice and Rats" prepared by Bionetics Inc. for the National Cancer Institute, shows clear teratogenic effects in two species of rodents which led to the military suspension of spraying in Exhibit #P0791 PIN # Date Author Addressee PB-223161 0 1 -Aug-68 RESEARCH BIONETICS FOR NCI & VOLUME III MUTAGENIC EFFECTS Description Volume III of Bionetics Report Prepared for National Cncer Institute entitled "Mutagenic Study". 15752 IV. B. 31 Exhibit #P0828 PIN # Date Author 00 01-Jan-69 E MRAK Addressee Secretary's and Description Paper entitled "Report of the Commission on Pesticides and their Relationship to Environmental Health." U.S. Department of Health, Education, Welfare, Washington,D.C. Exhibit #P0829 PIN # Date Author 30 01-Jan-69 J R M INNES Addressee Description Inns, J.R.M, et al., "Bioassay of Pesticides and Industrial Chemicals for Note, (1 969) . Tumorigenicity in Mice: A Preliminary "42 J. N A T 1L CANCER INST. 1101-14 IV. B. 32 15753 Exhibit #P0830 PIN # Date Author 35 0 1 -Jan-69 NONE NONE Addressee Status (1 969) . Description Contaminants Branch DFCT, "Current of the Chick Edema Factor Problem" Exhibit #P0863 PIN # Date Author 08 29-Oct-69 DR LEE A DUBRIDGE Addressee Description Press Release dated October 29, 1969 by Office of Science and Technology re: Restrictions on the use of 2,4,5-T Exhibit #P0873 PIN # Date Author 39 09-Dec-69 J W COOKE Addressee 1 969 Description Memorandum of Conference, December 9, IV. B. 33 15754 by Cooke, J.W. Exhibit #P0895 PIN # Date Author 43 28-Jan-70 NONE NONE Addressee Description Summary of Meeting January 28, 1970 re: Chick Edema Factor. Exhibit #PQ899 PIN # Date Author 40 06-Feb-70 A D CAMPBELL Addressee 1970, Description Memorandum of Conference, February 6, "Analysis of Chick Edema Factor in Pesticides," by Campbell, A.D. Exhibit #P0901 PIN #. Date Author 12 07-Feb-70 T WHITESIDE IV. B. 34 Addressee * D ''-` Description Whiteside, T . , "A Reporter at Large: Defoliation," THE NEW YORKER (February 1970). Exhibit #P0906 PIN # Date Author 41 11-Feb-70 NONE NONE Addressee Description Summary of February 11, 1970 meeting on Chick Edema as an Industrial Checmical Contaminant. Exhibit #P0913 PIN # Date Author 13 05-Mar-70 T WHITESIDE Addressee EDITOR OF NEW YORKER Description Whiteside, T . , "Letter to the Editor, NEW YORKER (March 5, 1970). Exhibit #P0916 PIN # Date Author 38 11-Mar-70 LAWRENCE FISHBEIN Addressee DR. HANS L. FALK Description Memorandum from Dr. Lawrence Fishbein to Dr. Hans L. Falk, "Meeting on Chlorophenols" (March 11, 1970). Exhibit #P0920 PIN # Date Author 16 17-Mar-70 DR J BURGER Addressee DR LEE A DUBRRIDGE Description MISSING DOCUMENT Exhibit #P0943 PIN # Date Author 14 15-Apr-70 DR JESSE STEINFELD Addressee SENATE SUBCOMMITTEE man subcommittee Description Hearing on the effects of 2,4,5-T on and the environment before the on Energy Natural Resources, and the Environment of the Senate Committee on IV. B. 36 1X u * Commerce, 91st Cong., 2d Sess. 167-89 (April 1970) (Statement of Dr. Jesse Steinfeld). Exhibit #P0957 PIN # Date Author Addressee 81 05-Jun-70 DR BERNARD JANDORF DIR RESEARCH LABS & OTHERS Bernard dated B. Description June 5, 1970 memorandum from Dr. Jandorf to Director of Research Laboratories, and memo routing slip June 10, 1970 from Dr. Jandorf to Dr. McNamara. Exhibit #P0964 PIN # Date Author 14.1 17-Jun-70 DR NED D BAYLEY Addressee BYERLY, DR T.C. Description Hearing on the Effects of 2,4,5-T and Related Herbicides on Man and the Environment Before the Subcommittee on Energy, Natural Resources, and the 15758 IV. B. 37 (June Environment of the Senate Committee on Commerce, 91st Cong., 2d Sess. 1-89 17, 18, 1970) (Statements of Dr. Ned D. Bayley and Dr. T.C. Byerly). Exhibit #P0987 PIN # Date Author 00 0 1 -Jan-71 A R ISENSEE Addressee JONES, G E applied 2,3,7,8Food Description Paper entitled "Absorption and translocation of root and foliage 2,4-dichlorophenol, 2,7-dichlorodibenzo-p-dioxin, and tetrachlorodibenzo-p-dioxin. J. Agric. Chem. 19(6): 1210-1214. Exhibit #P0988 PIN # Date Author 00 0 1 -Jan-71 K D COURTNEY Addressee MOORE, J A Description Published in the Toxicology and Applied Pharmacology, 20:396-403. IV. . 38 15759 Exhibit #P0989 PIN # Date Author 00 0 1 -Jan-71 G L SPARSCHU Addressee ET AL Teratogenicity Description Paper entitled "Study of the of 2,3,7,8-TCDD in the Rat." Food and Cosmetic Toxicology, 9:405-412, by Dow scientists. Exhibit #P0990 PIN # Date Author 00 01-Jan-71 R ROLL Addressee Mice" Description Paper entitled "Investigation of the Teratogenic Mechanism of 2,4,5-T With Food and Cosmetic Toxicology.9 :671 -676. Exhibit #P0996 PIN # 06 IV. B. 39 *''C O u i. t-- Date Author Addressee 11-Mar-71 DR COLIN M MACLEOD BALDESCHWEILER,JD & BRADY, NYLE C FARBER, EMMANUEL & KOTIN, PAUL MACMAHON, BRIAN & OTHERS Description Panel on Herbicides of the President's Science Advisory Committee, "Report on 2,4,5-T" (March 11, 1971) Exhibit #P1024 PIN # Date Author Addressee 00 0 1 -Jan-72 P C KEARNEY WOOLSON, A & ELLINGTON, C P JR chlorodioxins Description Persistence and metabolism of in soils, Environ. Sci. Technol. 6(12): 1017-1019. meat Exhibit #P1025 PIN # Date Author 00 01-Jan-72 M L LENG Addressee Description Paper entitled "Residues in milk and 1?. B. 40 15761 and safety to livestock from the use of phenoxy herbicides in pasture and rangeland." Down Earth 28(1):12-20. Exhibit #P1026 PIN # Date Author Addressee 00 01-Jan-72 MATTHEW MESELSON WESTING, ARTHUR H. & CONSTABLE, J D "Background the Description Paper of presentation entitled material relevant to presentations at 1970 meeting of AAAS. United States Congressional Record. 118:6807-6813. Mice Exhibit #P1027 PIN # Date Author 00 0 1 -Jan-72 D NEUBERT Addressee DILLMAN, I Description Paper entitled "Embrytoxic Effects in Treated With 2,4,5-T and 2,3,7,8-TCDD." Arch. Pharmacol. 272:243-264. IV. B. 41 15762 Exhibit #P 1035 PIN # Date Author 00 01-Jan-73 R BAUGHMAN Addressee MESELSON, M in Health Description Paper entitled:"Analytical Method for Detecting TCDD(dioxin): levels of TCDD samples from Vietnam." Environmental Perspectives. 5:27-83. Exhibit #P1036 PIN # Date Author Addressee 00 01-Jan-73 P C KEARNEY WOOLSON, E A & ISENSEE, A R HELLING, C S Description Paper entitled Tetrachlorodibenzo-p-dioxin in the environment: sources, fate, and decontamination." Environ. Health Perspect. 5:273-277. Exhibit #P1037 IV. B. 42 15763 Foie PIN # Date Author 00 0 1 -Jan-73 TON THAT TUNG Addressee Description Paper entitled "Le Cancer Primaire du Au Viet-Nam." Chirurgie. 99:427-436. Exhibit #P1038 PIN # Date Author 00 0 1 -Jan-73 ARTHUR H WESTING Addressee Assessment Description Report entitled "AAAS Herbicide Commission." Science 179:1278-1279. Exhibit #P 1039 PIN # Date Author 00 01-Jan-73 B A SCHWETZ Addressee ET AL Description Chapter concerning the extreme toxicity of the TCDD molecule. IV. B. 43 15764 Exhibit #P1040 Pin # date Author Addressee Description 00 01-j an-73 J B Greig ET AL Article published in Food and Cosmetics Toxicology Vol. 11, 585-595. Exhibit #P1041 PIN # Date Author Addressee 00 01-Jan-73 D NEUBERT ZENS, P & ROTHENWALLNER, A MERKER, HJ embrytoxic Description Paper Entitled: "A survey of the effects of TCDD in mammalian species." Environ. Health Perspect. 5:67-79. Exhibit #P1042 PIN t Date Author 00 01-Jan-73 J A MOORE Addressee ET AL Description Paper entitled "Postnatal Effects of Maternal Exposure to 2,3,7,8-TCDD. 15765 IV. B. 44 5:81-95. Environmental Health Perspectives. Exhibit #P1043 PIN # Date Author 60 0 1 -Jan-73 J B GREIG Addressee Description Greig, J.B., et al., "Toxic Effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin,ED. COSMET. TOXICOL. 585-95 (1973). Exhibit #P1044 PIN # Date Author 00 0 1 -Jan-73 F A SMITH Addressee ET AL Description Published in Environmental Health Perspectives 5:81-85. Exhibit #P1046 PIN # Date Author 42 12-Sep-73 D FIRESTONE IV. B. 45 15766 "Dioxins" Addressee Description Memorandum from Firestone, D . , (September 12, 1973). Exhibit #P1047 PIN # Date Author Addressee 00 01-Jan-74 A LANG EDITOR & NAT'L ACA. SCI. WASH., D.C. Description Paper as titled Exhibit #P1048 PIN # Date Author 00 01-Jan-74 J G VOS Addressee MOORE, J A Cellular Immunology. Description Article entitled "Suppression of Immunity in Rats and Mice by Maternal Treatment of 2,3,7,8-TCDD." Internal Archives Of Allergy and Applied 47:777-794 (1974) t y p tmf O V IV. B. 46 Exhibit #P 1051 PIN # Date Author 00 01-Dec-74 ROBERT BAUGHMAN Addressee THESIS University Description Paper entitled "Tetrachlorodibenzo-Para-Dioxins in the Environment. Highresolution Mass Spectrometry at the picogram Level." Published and filed at Harvard Library; Matthew Meselson Chairman Exhibit #P1052 PIN # Date Author 00 01-Jan-75 A R ISENSEE Addressee JONES, G E Description Paper entitled "Distribution of 2,3,7,8-TCDD in aquatic ecosystem." Environ. Sci. Technol. 9(7):668-672. Exhibit #P1054 PIN # Date Author 00 0 1 -Jan-76 ARTHUR H WESTING IV. B. 47 15788 of Sweden. Addressee Description Paper entitled "Ecological Consequences the Second Indochina War." Stockholm International Peace Research Institute. Almquist and Wiksell. Stockholm, Exhibit #P1055 PIN # Date Author 00 01-Jan-76 DIANE COURTNEY Addressee Description TOXICOLOGY,16:674-681. Published in BULLETIN OF ENVIRONMENTAL CONTAMINATION AND Exhibit #P1056 PIN # Date Author Addressee 00 0 1 -Jan-77 J R ALLEN BARSOTTI, DEBORAH A. & VAN MILLER, J P ABRAHAMSON, L J & LALICH, J J Description Paper en titled " Morphological changes in monkeys consuming a diet containing low levels of 2,3,7,8- XV. B. 48 15769 Cosraet. tetrachlorodibenzo-p-dioxin." Food Toxicol. 5:401-410. Exhibit #P 1057 PIN # Date Author Addressee 00 0 1 - Jan-77 J P VAN MILLER LALICH, J J & ALLEN, J R Chemosphere. Description Paper entitled "Increased incidence of neoplasms in rats exposed to low concentrations of 2,3,7,8 tetrachlorodibenzo-p-dioxin." 10: 625-632. Exhibit #P1058 PIN # Date Author 00 0 1 -Jan-77 THOMAS WHITESIDE Addressee at c l o u d ." Description Newspaper article entitled "A Reporter Large; the pendulum and the toxic New Yorker. July 25, 1977, pp 30-55. IV. B. 49 1X . <tJ " <v-< Exhibit #P 1059 PIN # Date Author Addressee 04 01-Mar-77 ALAN P POLAND MD DONALD SMITH MD & GERALD METIER PAUL POSSICK MD Workers in Description Poland, A . P . , Smith, D. , Metter, G., Possick, P . , "A Health Survey of a 2,4-D and 2,4,5-T Plant," 22 ARCH. ENVIRON. HEALTH 316-27 (1971). Exhibit #P1062 PIN # Date Author 00 01-Jan-78 ARTHUR H WESTING Addressee Cons iderations 27:285-294. Description Paper entitled "Ecological regarding 2,3,7,8-tetracholordibenzo-p-dioxin." Ecological Bulletin (Stockholm) IV. B. 50 15771 Exhibit #P 1063 PIN # Date Author 00 01-Jan-78 E E MCCONNELL Addressee ET AL toxicity Description Published article of the extreme of TCDD Exhibit #P1064 PIN # Date Author Addressee 00 19-Jan-78 MATTHEW MESELSON O'KEEFE, P & BAUGHMAN, ROBERT Possible Description Paper entitled "The Evaluation of Health Hazards from TCDD in the Environment." Symposium on the use of Herbicides in Forestry. Arlington, Virginia. 21-22 February, 1978. Exhibit #P1065 PIN # Date Author Addressee 00 01-Jun-78 WHO IARC MONOGRAPH & WORLD HEALTH ORG. 15772 IV. B. 51 INT'L AGENCY CANCER Description International Agency for Research on Cancer, Sponsored by the World Health Organization Study on Polychlorinated Dibenzo-P-Dioxins and Polychlorinated Dibenzofurans. Exhibit #P1067 Pin # date Author 00 04-sep-78 Thomas Whiteside Addressee Description Article in magazine on the effects of defoliation in Vietnam and the massive spraying of herbicidal poisons. Exhibit #P1068 PIN # Date Author Addressee 00 01-Jan-79 L A SHADOFF HUMMEL, R A & LAMPARSKI, L DAVIDSON, J H 2,3,7,8-TCDD Description Paper entitled "A search for in an environment exposed annually to 2,4,5-trichloro-phenoxyacetic acids ester(2,4,5-T) herbicides." Bulletin IV. B. 52 15773 Environ. Contain. Toxicology, in press. Exhibit #P1069 PIN # Date Author 00 01-Jan-79 ARTHUR W GALSTON Addressee of does and ecosystem Description A r t i c l e which d e s c rib e d the p e r s i s t e n c e TCDD in th e s o i l , t h e f a c t t h a t TCDD b i o a c c u m u l a t e in th e human f a t t i s s u e m ilk , and th e harm to our e n t i r e from th is extremely t o x i c substance. Exhibit #P1070 PIN # Date Author 00 01-Jan-79 R E FAITH Addressee LUSTER, M I Description TCDD is immunosuppressive Exhibit #P 1071 IV. B. 53 i JL lj v ^& Science PIN # Date Author 00 0 1 -Jan-79 ARTHUR GALSTON Addressee Description Plants, People and Politics. Bio. 20-7:405-410. Exhibit #P1078 PIN # Date Author DOW33791-836 0 1 -Nov-79 ALVIN ET AL YOUNG Addressee PUBLISHED Description Monitoring": Paper entitled "Herbicide Orange Site Treatment and Environmental Summary Report and Recommendations for Naval Construction Batallion Center, Gulfport, Mississippi, dated November, 1979. Exhibit #P1079 PIN # Date Author 00 0 1 -Jan-80 ARTHUR W GALSTON Addressee description Book describing the life, death and IV. B. 54 their diseases of the green plant including sex lives and reproduction cycles, and their cancers. Exhibit #P1080 PIN # Date Author 00 01-Jan-80 ARTHUR W GALSTON Addressee Academic Description Article entitled "Herbicides" in American Encyclopedia. Arete Publishing Co., Inc., Princeton Forrestal Center, Princeton, New Jersey. Exhibit #P1081 PIN # Date Author 00 01 -Jan-80 ARTHUR W GALSTON Addressee KAUR-SAWHNEY, R Plant Description Article published in What's New in Physiology. 11:5-8. IV. B. 55 15776 Exhibit #P1082 PIN # Date Author Addressee 00 0 1 -Jan-80 ARTHUR GALSTON KAUR-SAWHNEY, R & FLORES, H E Description Paper entitled "Polyamine-induced DNA synthesis and mitosis in oat leaf protoplasts." published in Plant Physiology. 65:368-371. Exhibit #P1083 PIN # Date Author 00 01-Jan-80 CINCINNATI EPA Addressee R AND D Description Document published by the Research and Development Office of EPA Concerning the "Most Toxic Chemical Ever Synthesized by Man" Dioxin (2,3,7,8-TCDD). Exhibit #P1 084PIN # Date Author 00 0 1 -Jan-80 PHILLIP E ENTERLINE IV. B. 56 Addressee r-y (*< Description Published in Chest 78:2, AUGUST, 1980. Exhibit #P1090 PIN # Date Author 29 06-May-80 PHILIP HANDLER Addressee GEN MURPHY A CHESNEY Following with General Description Review of U.S. Air Force protocol: Epidemiological Investigation of Health Effects in Air Force Personnel Exposure to Herbicide Orange (1980) cover letter from Philip Handler to Murphy A. Chesney dated May 6, 1980. Exhibit #P1093 PIN # Date Author Addressee 90035 27-Apr-81 WILLIAM GAFFEY ROUSH, G JR MD & ET AL Description Report on Dr. Moses report on Selikoff Study, while the reporter notes the abmornal clinical findings is careful to 15778 IV. B. 57 describe them as "Anti-Climatic. Exhibit #P1 094- Pin # 00 Date 24-Jun-81 Author Raymond Singer Addressee ET AL 7 PUBLISHED Description Paper entitled "Nerve Conduction Velocity Studies of Workers Employed in the Manufacture of Phenoxy Herbicides." Academic Press, Inc., Environmental Research 29:297-311(1982). Exhibit #P1095 PIN # Date Author 00 29-JU 1 -8 1 FIFRA EPA Addressee DOCKET SHEET during FIFRA plaintiffs. Description All testimony and exhibits produced the EPA'S cancellation hearing under may be used at time of trial by 1?. B. 58 15779  Exhibit #P1097 PIN # Date Author 00 0 1 -Jan-82 ALASTAIR HAY Addressee manufacture the processes spraying quantities documented Agent Description A comprehensive history of the of chlorinated phenoxy herbicides in United States and abroad;the chemistry, biochemistry, and manufacturing of these chemical compounds; the of these herbicides in massive during the war in Vietnam; other human exposures; the harmful and toxic effects resulting from exposure to Orange, 2,4,5-T and dioxin. Exhibit #P 1100 PIN # Date Author 00 01-Jan-83 BIBLIOGRAPHY DIOXIN Addressee CHRONOLOGICAL ORDER plaintiffs' Description These articles may be used in IV. B. 59 15780 prima facie case Exhibit #P1101 PIN # Date Author 00 0 1 -Jan-83 MAUREEN HATCH Addressee DOCTORAL THESIS deposition a of Description Dr. Hatch has submitted at her copy of her doctoral thesis at Columbia University on the Reproductive Toxicity TCDD. Exhibit #P1102 PIN # Date Author 00 06-Jan-83 SOLID WASTE EPA Addressee PUBLISHED DRAFT Office by Assessment Description Draft document prepared for the EPA of Solid Waste and Emergency Response, the Environnmental Criteria and Office, Cincinnati, Ohio 45248 entitled "Health and Environmental Effects for: Tetra, Penta and IV. B. 60 Hexachlorodibenzo-p-dioxin. Exhibit #P1103 PIN # Date Author 00 07-Jan-83 AIR QUALITY EPA Addressee DRAFT PUBLISHED Description of known entitled Environmental Cincinnati, An overview on the health problems associated with dioxin, including the routes of possible human exposure, laboratory animal data, and conclusions the extreme toxicity of the substance as 2,3,7,8-TCDD or dioxin. Paper "Research and Development, Health Assessment Document on Dioxin for the Office of Air Quality, Planning, and Standards, prepared by the Criteria and Assessment Office, Ohio 45248. Exhibit #P1104 PIN # Date Author 00 0 7 -Jan-83 WATER OFFICE EPA IV. B. 61 Standards 45248 Addressee DRAFT PUBLISHED Description 1983 Draft of EPA Document prepared for Office of Water Regulations and by the Environmental Criteria and Assessment Office, Cincinnati, Ohio after Peer Review in July 1983. Exhibit #P1108 PIN # Date Author 00 01-Jan-84 ARTHUR GALSTON Addressee UNPUBLISHED effects the spraying of War; 2,4,5-T Description Chapter submitted on the auxin-like of TCDD on plants; the devastation of Vietnamese countryside from the herbicide Orange during the Vietnam extrapolation from plants to humans in assessing the horrible risks of the spraying of massive quantities of contaminated products. IV. B. 62 Exhibit #P1109 PIN # Date Author Addressee 00 01-Jan-84 ALASTAIR HAY MURPHY, SEAN & ROSE, STEVEN Description Book describing the devastation of the use of manufactured poisons which are indiscriminately sprayed on the third world. Exhibit #P1110 PIN # 00 Date 01-Jan-84 Author BIBLIOGRAPHY HAY Addressee LIST OF CITATIONS & LIST OF BOOKS LIST OF ARTICLES & BY HAY BY OTHERS Description The attached references are cited in Dr Hay's summaries and curriculum vitae and will form the basis of Dr. Hay's testimony. Exhibit #P1111 IV. B. 63 upon in PIN # Date Author Addressee 00 0 1 -Jan-84 MARVIN SCHNEIDERMAN LIST OF CITATIONS & LIST OF ARTICLES BY AUTHOR & BY OTHERS Description Dr. Schneiderman has cited references which he may rely in whole or in part forming his opinions. will her Exhibit #P1112 PIN # Date Author Addressee 00 0 1 -Jan-84 ELLEN SILBERGELD LIST OF CITATIONS & LIST OF ARTICLES BY AUTHOR & BY OTHERS Description Silbergeld has submitted numerous references, including her own original works and the works of others which form in whole or in part the basis of opinions at trial. Exhibit #P1113 PIN # Date 00 01 -Jan-84 IV. B. 64 15785 Author Addressee RONALD KERMAN LIST OF CITATIONS & LIST OF ARTICLES BY AUTHOR & BY OTHERS Description Dr. Kerman has submitted comprehensive lists of references including his own articles and those of others which will form in whole or in part the basis of his opinions. Exhibit #P1114 PIN # Date Author Addressee 00 01-Jan-84 ALAN LEVIN LIST OF CITATIONS & LIST OF ARTICLES BY AUTHOR 4 BY OTHERS works testimony. Description Dr. Levin has submitted a comprehensive list of references including his own and those of others which will form the basis in whole or in part of his Exhibit #P1115 PIN # Date Author 00 01-Jan-84 ALAN LEVIN IV. . 65 ^5786 Levin Addressee SPOHN, RICHARD & CHAPTER OF BOOK SUBMITTED & FOR PUBLICATION Description Chapter of book submitted by Dr. Alan for approval to the board of Medical Quality Assurance by the Society for Clinical Ecology (Northern California Chapter). Exhibit #P1116 PIN # Date Author Addressee 00 01-Jan-84 ALAN LEVIN MEDICAL RECORDS & OTHER PATIENTS Description Self Explanatory list and Exhibit #P1117 PIN # Date Author Addressee 00 01-Jan-84 MARVIN LEGATOR LIST OF CITATIONS & LIST OF ARTICLES BY AUTHOR & BY OTHERS Description Dr. Legator has submitted an extensive of references including his own work IV. B. 66 151? will those works of others upon which he base his opinions and his testimony in whole or in part. Exhibit #P1118 PIN # Date Author Addressee 00 01-Jan-84 MARVIN LEGATOR NOTEBOOK & DIOXIN CITATIONS EXHIBIT DEPOSITION abs tracts and Description Dr. Legator has submitted his personal notebook of dioxin citations and which was an exhibit to his deposition in possession of all parties. list will Exhibit #P1119 PIN # Date Author Addressee 00 01-Jan-84 LENNART HARDELL LIST OF CITATIONS & BY AUTHOR PUBLISHED Description Dr. Hardell has submitted an extensive of his own scientific articles which IV. B. 67 15738 form the basis of his opinions, as well as his underlying 25,000 pages of questionnaires to the defendants. Exhibit #P1120 PIN # Date Author Addressee the basis of in Description 00 01-Jan-84 RAYMOND SINGER LIST OF CITATIONS & LIST OF ARTICLES BY AUTHOR & BY OTHERS PUBLISHED Dr. Singer has submitted a list of references including his own work and work of others which will form the testimony and the basis of his opinions IV. B. 68 1 5 h/ 8 9 A i DO MIDLAND, MICHIGAN July 25, 1967 W. J . McCoy ' Bioproducts Sales - BPC -v' c c : W. L . Corbin, BPC iv-j-' >-v-. K tU z 05 O 0 O' o vO -\J nO .V 2 ,4 ,5 - T FORMULATIONS I appreciate v e ry much your note of 7 /1 7 /6 7 in which you informed me that some Diamond m aterial has apparently caused seriou s skin prob lem s among people applying the m ate ria l. This goes along with a report that recen tly appeared in the South A m erican lite ra tu re which states that m aterials of this nature have also bean noted to have caused sim ilar difficulties.-;.I am enclosing a copy of this publication .fo r your inform ation. ' '-'.=1- 7 ,*7 :7J It to would come appear that our predictions of a few years ago to pass, unfortunately. Frankly, I am mighty a re beginning glad that we took the position we did. . -:.y '`i P le ase continue to keep me informed as best you can. <$ <*1- fr'ifvr ` ' i.-. . > - *-V V. K. Rowe Biochem ical R< 1803 Building pgw rch Lab oratory b c c :- ^ . K. Rowe (2) - ^ Correspondence w**. V ' . r m 1 ^ efr-1-- v* -. l-- "*r.' -V 4 15798 Biochemical Research Laboratory The Dow Chemical Company OFFICE COPV HLORACNE PROBLEM AT ORT SASKATCHEWAN PLANT, O W CHEMICAL OP CANADA Pile: T2.1-18-2 Date: 3/21/69 By: L. G. Sllverstein OW746398 Date Date ? - 7 - f <? ? *7 cr* o "Vi O S . PROBLEM Workmen in Fort Saskatchewan have experienced chloracne. 'here may be another skin rash problem related to the weed killer peration but this has not been diagnosed definitely by a physician. , FINDINGS 1. An acnegen was found to be present in some process samples, \ specifically the Dowlcide G product in the reactor and the Dowlcide G product at the packaging location. In addition, a sample of crude dlchlorophenol showed slight to moderate activity, and the caustic insolubles in the G Liquor settling tank showed severe acnegenic activity in the rabbit test. ?. No acnegenic activity was found on a series of wipe tests taken In the G and weed killer building. laboratory studies on the decomposition cf chlorinated phenols have indicated the definite possibility of an acne hazard from overneated cr decomoosen materials. RESTRICTED: for use within The Dow Chemical Company only. 15797 G6C9PI 2 CONCLUSIONS There is not enough exposure during normal operations to active materials to explain the degree of chloracne seen in workmen at Port Saskatchewan. The housekeeping observed and in the wipe samples I collected during my visit in October of 19^5_indicated satisfactory housekeeping in the penta and weed killer plant. Unusual exposure from maintenance or clean-out of equipment such as the cryer, or from accidents such as overheating of the dryer may have caused the severity of skin reaction noted in the workmen. Fersonal cleanliness is of primary importance in avoiding skin problems and minimizing their severity once encountered. The instructions on the second page of tfce operator's manual for rr. Saskatchewan should be followed conscientiously: "Dow wili provide a complete change of clothing for each operator, each day- This clothing including shoes, hats and gloves must re left in the lockers provided. To assure adequate cleanliness ^nd hygiene, a shower must be taken by each operator prior tc :;s leaving the Company premises at the end of each shift." *scussions during my .,.:>l.t in October, 1965, indicated that i" ' pr. secure had been r^iaxeo or at least net enforced by 15798 1 supervision. It is my firm opinion that this is the most important step that management can take toward improving the situation. . Any unusual exposure should require immediate and thorough shower and change of clothes from the'skin out to minimize the probability of injury. If exposure to airborne fume or dust, for example from the dryer during clean-out, is to be encountered, an air supplied hood shouic be a required item of clothing. . Men should net be allowed to work in the e vicinity of such an unusual exposure unless they too are protected from inhalation of the airborne material. f>. A clinical definition of the skin rash described by Kasanovich would be very helpful in determining if there is a second problem on the weed killer side." 7. Skin condition of the workmen afflicted should be followed clinically in order'" to determine 3f progress is being made in eliminating the skin condition. 02 O o 'S9 3 1 I W - O vj r TL'`*.. v\ "Dowicide bumps," . " chlnrarie, is a skin condition Pj characterized by blackheads and bumps apnearing on the face c*f the individual afflicted, sometimes spread i-pg to other parts of BB the body. The condition has been recognizee for many years as ^ j a n occupational hazard in the production f Towle ides, especially Dowicide G fs^c.ium renzachloi-ophenate). jjj Fort .-.aSantcr.ewan Dowicice ore-.-, ction plant has exDeriencec an outbreak of ch3oracne in its v.wrv.men. Te3ts on *cess samples fr'm Fort Saskatchewan are summarized in Table 1. i A series of wipe tests in the ; 't .Saskatchewan plant are summarized in Table 2. All wipes were free of activity jjindicating that at the time of the sur'-ey housekeeping was good. The mile activity of orccess and proruct samoies, and Pjthe lack of the activity ir, wipe samples, ulus the physical nature cf the most likely exposure: that is, the solid Dowicide G; make jilt difficult to rationalize the severity of the chloracne in gworkmen at Fort Saskatchewan if their exposure was "routine," chat is, to the normal orocess materials during normal operation P|;f the plant. On the other han :, o.... . msc to theivcaustit oiubles in the G liquor Tar-, an-u Be ; decomposition products ^f ;w 1c Tie <; in i of animal response v laboratory study n cn o i 15800 n*f.v*TajrM s'jniT.2 r1zeb in Table 3 indicate the possibility that nonroutine ^exposures to overheated Fowicide G or its furies either during malfunction cf the dryer or the residue in cleaning out the jjdryer, or oerhaps cleaning out the G Liquo~ settling tank may have brought on tne pronounced chloracns?- in the persons affected. | From the description of his rash by Peter Kasanovich there may be a seconc skin problem, related to the weed killer Jjjoperation. This needs clarifying by a clinical examination of tjy^ men. According to Peter Kasanovicn the rash appears and :|1 saopears rather promptly and is related tc: working and being off -work on week-ends. This is not characteristic of chloracne. TM I t does sound like a rash which occurred in Midland many years ago a n d was associated with 2, '--1? oroduction. V.'hen a bleaching step was added to the 2,^-D process to remove odor and color the rash ^disappeared along with improvement of the product. Careful attention to nousekeeoing and personal cleanliness B m a v eliminate this Droblem. --w 9 3 g ittiOl 15802 y *' i0 mbe r Sample P e s e r l p t I o n s 1 Crune DCP from r e a c t o r 1 Same, 5 0 * in CHCl^ S t i l l bottoms from SBS 2 Same, 5 0 * in CHCl^ *3 1 ' e c t o r e f f l u e n t from bottom out . .::;e, 5 0 * in CHCl^ `i ' l l led s t i l l bottoms from V-2u . B'Hf in CHCl^ \i>] ni c h i .? " lran;' a a fines BO* Jn CMC1-j ? ` a bea Ms Bao.o, f>0* In OHCl^ Pelila 'S-1 OS from r e a c t o r Same, 5 0 * j n c u c i Dow y to G b a t c h 104 Same, 50; in CHCl^ Unoiled penta from fla k e r (65405) Same, 5 0 * In 0H01-. f} Animal Permonses F o l l i c u l i t i s Burn None SI-Mod None None None None None None None No ne None If rie S I -M ori Slight None Slight Slight Slight SIirht S 1 ight None SIIght Yes Yes Yes Yes No No Yes Yes Yes Yes Ye s Yes Yes Yes Yes Yes Yes Yes Yes Yes No Yes Mo . Cf Appl. Day s Vx o o s u r e 3 24 4 11 3 35 4 24 15 24 17 3 3 4 39 2 38 1 39 1 24 "3 -, 3 11 4 11 4 1 24 4 14 2 3 o 1: 2 1: 10 2' 3 1.. Ug TCBD/gm VPC A n a l y s i s <y 1^ <1 <1 <1 *-- 0 0 Hr; tested : 1 0 0 * .da ' 'A5 1 0 0 * dai i/o ' 1 0 0 * dal /I OO * 1 i 1DOT. da 1 . 1 J 100* da' i/r. 1 * 100* dm 5 '/e> 1 ) 1 0 0 % d a ' (./:/'' 6 1 00* dal ------ ' 13 1 0 0 * dal , / ./ A... . Table 2 . FOR? SASKATCHEWAN VI?? SAMPLE' L. G. SIU/EHSTFIN D ' /f'-i -- penta S i i l e and Cent rei low i o l e ? 7 tagiir.r; ---- handing Dcv.'ic i c e ,c b--c" lr j -- h a n d l e s . Door to :arehouse -- h a n d les . Ha nd r a i 1 to sec-'-nd f l o o r , r . - r t h r::; f .'7;.l F o l i c in." F l o o r -- doorway o- tw^en washreo 'i : " ar." lock*? Fleer -- ctjc pv;ay A;t.v.^ G classifier olat form. .0 12 4. 15. J.O . ( ~r 8. m. Valves near cher:v e tan--: .ra . Pine rear lanvinc, :v..rt.h *sairway Latch (.f penta reactor samri.^ box. ~-.il E Handles of flaker oorts. Operatc-r's desk -- penta reactor rox., jcond floor. Drier -- handles. Doer tc c intro I room from oenta r-?'t'.:~ -bcr., Benchtops in control roorr.. One rater's desx and clln boards. co-'T:'.' -v.om. Tools ir. drawer -- control "vom. Valve handles in G reactor c5Ice are. - hwest corn" of G reactor -- handles, second fl..r vote de. r'eed Killer Side II. Stair treads -- first floor rein^ 'raxed with tar). 22. >3. Handrail, first to-..second Valves and handles on leves le .c o n d fl-. or. Sample hood, second floor -- front lio and valve handle" . 25- Valve handles on LUV.'A evanorator, third level. o" y V2 -CP JO *u 15803 \ able 3. IABORATORY 5"UT CHLORCPEKNOuS C.Y TARMAI, DROOMFOSITION OF amnie umber t Semole Description 11 Sodium 2,9-d Ichlorophena te re s1du 2 Sodium 2,-dlchlorophenate fume condensate *3 Sodium o-chlorcphenate , fume condensate u Powicide F fume condensate --> Dowicide G fume condensate 0 Sodium 2,ii-dichloronhenate contro 7 Sodium 2,U-dichloroDhenate he Id 7 hours at 150C 8 Sodium 2/i-dichloroohenate hs I 7 hours at 170C 0 Dowicide G control lo Dowicide G held '( hours at 170 c 11 Dowicide G residue from overheate sample from 265 Fullding, belov; grate in fluid bed dryer No. AD p i . / No. Days 10/19 Rabbit Response Moderate 13/22 S 1 -Moc -?i 7/11 iU '21 S 1-Mod Severe Seve re ' 6/22 None ] c /22 None V1 1 16/22 10/1 Slight None Slight L2/l3 Moderate <*n +U CD O -cn 15Q04 l) 0 0 3 1 C4 y ~ *-(/ o o J TOXICOLOGY RESEARCH LABORATORY HEALTH AND ENVIROIJMEIJTAL RESEARCH //DOVJ CHEMICAL C.S.A. . MIDLAND, Mi'CIITGnE> 4 8 6 4 0 V Ni VM ro CD o TESTIMONY FOR THE 2,4,5-T HEARING I . by . V . K . Rowe f &*.*.* 30J iNTRODUCTio:: DOW 7G05G0 i i r i i i fl I The purpose of this testimony is to provi-dc background informa tion that will be useful i n "considering the testimony from Dow and other scientists'. 1) ' It- will state briefly seme of the basic concepts in toxicology. 2) It will outline the history of toxicological and environmental health research in The Dow Chemical Company. 3) It will discuss the development and use of toxicological and related data. 4) It will describe the development of Dow toxicological information on 2 , 4 , 5 - trichlorophenoxy acetic acid (2,4,5-T) and 2,3,7,8-tctrnchlcrodibonzo-p-dioxin (TCDD) up to 1970. It will not include a discussion of the studies that have been conducted since 1969 as they will be presented by others. I 2- I 760561 I I ) Basic Concepts of Toxicology Webster defines toxicology as "a science that deals with I poisons and their effect on living organises, with organisms, I with substances'otherwise harmless that arovc toxic under particular conditions, and.^with .the .clinical, industrial, l o g a O I or other problems involved." I Webster defines Toxicity as "the quality, state, or relative i degree of being toxic or poisonous." It is worthy of note that Webster recognizes a relative degree of toxicity, because I this concept is too often overlooked in evaluating "toxic hazard", or the probability of an untoward effect occurring. I This latter concept is recognized in the definition of 1 toxicology. I Further, there is no such thing as a nontoxic material. All I materials are toxic--it is only a matter of how much and under what conditions they are encountered that determine I whether a real-life hazard exists. In industrial toxicology, we are continuously determining both the qualitative and the quantitative aspects of materials to cause adverse effects. i Based on such basic information and with knowledge of condi tions of use, it is possible, within reason, to predict trie a consequences of given situations. Thus a material may be crmuitc aijovmnri.ato (s.jfe) for a particular epplicutio:. but a <-'-.*< -'V *.'*'*'------------ - . V ''VriT.-. - - i 2 W Wi j " K $ T ] r 7 ' rTQCno tA ^ ^ 0 - :i- quitc inappropriate (hazardousi for another application. in other words, the risk is judged to he acceptable or unaccept.;;,!o depending upon circumstances. The toxicity of the material has not changed-- it is the same in both situations bat the likelihood of excessive exposure is different in the two situations, being too great in the second situation. Tox-icoloyists are well aware that toxicity information,developed in animal studies : V'; fi-' ' cannot always be used to assess directly what may occur in man. Nevertheless, based upon my experience in the field of toxi cology, I can only conclude that predictions based on appropriate animal studies have been remarkably accurate and have served mankind well. 11) History of Dow Toxicological a nd P.clatc-d Research It was only a relatively short time ago, say 45 to 50 years ago, that what wo think of as "industrial toxicology" or perhaps more appropriately termed "preventive toxicology" was nonexistent for all practical purposes. "Forensic or diagnostic toxicology" was, of course, well known but its capabilities* were severely limited as measured-.by standards of today. Organised laboratories for determining the toxicity of substances before the fact were not known. Medical people tool: care of persons after the fact. There was little preventive industrial medicine, b'-^ausc there was little toxicological data upon which, to bare a preventive medical program. That was tin.- state of the art in 1933 when bow hired its first, b io c h e m i s t , F-r. Don 1).. Irish, because the *. .. -4- late Dr. Willard H. Dow, son of the founder of our company, in his far-sighted way, thought that someone trained in the biological-chemical area ought to be useful to a chemical company. Less than a year later, a fatal accident occurred as a result of an acute skin exposure to a chemical. a 0 Dr. Irish identified t h e :culprit ;Vs'' phenol , studied its effect on animals both qualitatively and quantitatively, and set-up operating procedures and an educational program designed to CD o 'CM a: CO prevent-any reoccurrences. Dr. Dow charged Dr. Irish with the respcnsiblity of examining new and old materials so that the unexpected would not occur. Thus, the Toxicology Laboratory of The Dow Chemical Company was born and it has flourished ever since under essentially the same but broadened charter and with the full support of Dov.' Management. By 1936, Dr. Irish had outgrown his garage and construction shanty laboratory and was given a wing in a new laboratory building. These facilities served us well for almost 20 years. In 1955, we moved into a completely new .building of about 40,000 square feet dedicated wholly to biochemical research, including 14,000 square loot for toxicological research. In 19G0, another new building, approximately 5200 square feet, a dog kennel capable of handling 200 dogs was added. The % . h'-tf-i- h;.-. !>9S09i ^ O Q I i need for toxicological data continued to grow and in 1966- 1 1967 Dow built a new 30,000 square foot 1.1 million dollar I building committed wholly;to toxicology. In January 1974, ground was broken for an additional 47,000 square feet of I laboratory space. This new space, costing approximately 4 million dollars was.idedicited In May 1975 giving Dow, at I Midland, Michigan one of the finest and most modern i toxicology research facilities anywhere in the world. As of January 1976, our present staff in toxicology consists of I 109 persons. . The present staff includes 20 persons with the I doctorate degree including 7 who also have the DVM degree, 28 with baccalaureate or masters degree, 5 non-degree I specialists, 22 working toward their baccalaureate, 23 i animal caretakers, a secretarial staff or 8 and 3 hign school student co-ops. In addition, we have a staff of 20 i industrial hygienists associated with our laboratory, 6 of i whom are fully certified by the American Board of Industrial Hygiene, and 8 industrial physicians located in Midland. Also, we have a sizable Pathology and Toxicology Research I Laboratory associated with our pharmaceutical business located in the Indianapolis,Indiana area and a new Biomedical- Toxicology Laboratory at our Texas Division in Freeport, Texas. :<* " ' - '/ ~ , 7*- . - - - ~ - -VV ; -T:--'l - -i?V.' --ri v t-'jsw s'r * vtrV: i.-.-r -G- .About 1937, it became* obvious that if v;e were to effectively apply our toxicological information, we needed to know more about the actual environmental conditions. This meant care ful analysis of the workroom environment for the presence of excessive amounts of chemical substances,' heat, ionizing and nonionizing radiation, noise cr any other condition with which we might be c o n c e r n e d , S u c h 'environmental studies have oo <? . developed into what is now called industrial hygiene. The Dow Industrial Hygiene Laboratory developed as a part of the Toxicology Research Laboratory. C3 O CJ1 CcTni As toxicology and industrial hygiene evolved in the direction of control of the environmental health problem of Dow's working people, we developed close cooperation with the Medical Department and Safety Department. It is obvious that the studies of environmental circumstances by industrial hygienists needed to be coordinated with medical surveillance of the people in that environment. While the safety engineers emphasized mechanical hazards, the industrial hygienists emphasized chemical hazards and ether physical stresses. It is obvious that the interests of the four groups, Toxicology, Industrial Hygiene-, Medicai and Safety are quite inter-related and complement one another toward a vrtj.::* goal, a safe place to work. 99coq t MOn -7- As soon as we wore developing "effective toxicological /information and knowledge of the environmental circumstances ; v/ithin our production plants, it became obvious that this type of information would be useful to our customers as well. As the years passed, such information on our products became more and more important. -It/is interesting to note that in the mid-thirties.we almost never received an inquiry on the handling problems of a particular chemicaj. but by the forties, ;such requests were common, and by the fifties, .it was usually ' one of the first pieces of information requested on a material,particularly, if it was new to the inquirer. Today, such information is not merely requested, it is demanded, not only by the customer as a condition of doing business, but by governmental regulatory agencies prior, in many instances, to doing business in certain areas. Earlier I spoke about toxicology and industrial hygiene evolving as needed to meet problems in occupational or environmental health. The very same thing has happened in all of the areas of science with which I am familiar. What this really means is that our tools of the trade have become sharper and sharper and I have no doubt that this will continue. I have no question that the techniques we view as being sopkisticated today, will be commonplace in 2 or 3 years and many of them will be obsolete in 5-lO^ycars. " ' -- - -- v . - *.' - c .......1 i .v. I f VlUrfetJ >-S-i -a- W 760567 This is the pattern of scientific-progress. For example, the need to develop a laboratory test to identify materials with a capacity to cause chloracne in man was recognized early in our laboratory's history because some of the work men were experiencing mild cases of the disease. The disease was not a new ohe, having..'been'identified in Germany in 1899 although.it was referred to as folliculosis caused by chlorinated hydrocarbons. In the following years, there were occasional reports of chloracne but in 1937, several articles were published relating to the development of chloracne and liver injury caused by exposure to higher chlorinated naphthalenes and biphenyls. No method was then known by which materials having this property could be identifier. Consequently, we began searching for such a method that we could use to test new chemicals for their chloracriegenic potential. This research resulted in the development of the "rabbit ear test", a description of which we published in the January, 1^41 issue of Industrial Medicine. It was entitled 'THE RESPONSE OF RABBIT SKI!.' TO COMPOUNDS REPORTED TO HAVE CAUSED ACNEFORM DERMATITIS and was authored by E. M. Adams, D. D. Irish, II. C. Spencer and V. K. Rowe. t* - The response of the rabbit car tc ehlcracnegens is characterized by a thickening of the'ear, excessive exfoliation having a granular consistency and most characteristically enlarged ' V ;. *. .-T a ***it-.*v * * ~ \ - ul -`*I*v *` r " '-iil*-*' V * j r '- r.r af . * .'V a V. ": * 5 ^ - hair follicles from which horn tin and sebaceous matter r.a*/ bo expressed leaving pits up to~l-2 mm in diameter. Thin '"rabbit car test" is still used in our laboratory and in D O W 7G0568 many others as well. It is a very'reliable test which has . stood the test of Lime- It served us well in dealing with the problem we nad in 196*1 in t^e ^production of 2,4,5-tri- ' . chlorophenol. : 'i! f*. .'. : ' > .. 'Another excel]ont example of science's response to need is V in the field of analytical chemistry. I remember well, my ...trying, about 30 years ago, to get the analytical specialists to give me results- with'a sensitivity of 1 ppm of an organic compound. They threw'.up their hands .in despair and usually said that they probably could get to 100 ppm, they might be able to go to 10 ppm but 1 ppm was out of the question. Nevertheless when there was a recognized need for greater sensitivity, it was accomplished. Just a very few years ago we considered analytical methodology with a sensitivity of one part per billion as extreme, and it was. Now, in son0 areas, we are tal':ing about parts per trillion.. The same situation prevails in toxicology. Our methodology has improved along a road parallel to that of the analytical chemists. Some of the methodology used a few years ago is inadequate by today'.; standards, some that is adequate today wj 11 be inadequate ?, few years hence, and .so it will be as time'goes .on-.-as the needs develop, science w i l l find a way to meet -10- aa o n ln all cases, methodology is only-a tool employed to generate; data. The application of such data in the solution of real life problems requires a knowledge of the limitations of the data, a knowledge.of the real-life situations to which the data is to be applied, and the exercise of good judgment based on v* 1* . .. r\. ./ . the rule of reason. ; ... . ' - -' I have spoken about Dow's commitment to toxicology, cr> O CJl 03 CO industrial hygiene and medical surveillance programs. I.want also to describe a related effort which has as its objective the conservation of the quality of our environment. Late in 1969, the Dow Board of Direcrors decided that not enough was being dene t.o avoid introducing undesirable'materials into the environment. Tt decided to accelerate Dow's efforts in this area by appointing a company wide Ecology Council. Many of. Dow's top executives were members, of this council. In rapid succession, ecology councils were created in manufacturing areas and in product departments.. Those councils were charged with the responsiblity of examining everything within their domain to determine whether it con stituted a problem if released to the environment and if so, to correct the situation in the best way possible. This charge encompassed products, with consideration being given tc the various uses of a product, by-products and wastes. . . . . . . . J 5815, . -11- Thus Pol 1ut ion Aha terror,i became the watchwords of tue produc tion managers and Product Stcw.irdship-bocar.o the watchwords for research, development and sales personnel. 0i-S9?lbAoa Many prohlens and questions were generated. _Where solutions were readily apparent, corrective ac tf i.o\n *was instituted. As expected there were many'Situations identified where * i there was no data available and hence an unknown existed and questions could not be answered. In an effort to bring the technology and expertise available within Dew to bear on this problem, Dr. J. E. Johnson, than Vice President and Director of Research and Development, speaking for both Dow Corporate Management and Dow Chemical U.S.A. announced on April 21, 1971,the creation cf an Environmental Testing Advisory Board, dubbed ETAB for short. The announce ment stated the objectives as follows: The board will servo as Dow's technical authority advising all functions and mnnngorr.ont levels on the possible environmental effects of products and new or changed processes. It will also advise on registration requirements and on customer and public environmental safety needs. The board will function under the broad direction of the company Ecology Council. . Specifically, the board will: --establish siandarcinod test procedure;;. These procedures will be useful no determine and predict possible environmental affects cf onecrimen tel and existing products and new or changed processes. ;/v i 5 8 i 6 :: 1r--' -..J1 f' .- 1 ,1 .... v ;i VI * ) -l- > j " -12- D O W 760571 -- assess capabilities of. both Dow and nen-Dow laboratories and identify these host able to conduct specific environmentally related experiments. -- serve as a repository for data acquired from studios conducted outside of Dov;. -- help interpret experimental results. -- provide advice and recommendations concerning environmental testing matters. ' The ETAB board was interdisciplinary-, in character and- consisted V`V . " ' of persons who had the.best knowledge available about the problems the board was asked to solve. Many subcommittees were formed under the leadership of board members and work commenced. In January of 1972, a compilation of the best methodology available entitled "ETAB - Environmental Testing Manual" was issued. This manual describes procedures to be followed in assessing environmental effects and describes about 150 tests that can be used to help evaluate such factors as toxicity, bioaccumulation, movement, and stability of materials. During the next several-months, a team(s) experienced in the use of the manual to solve environmental related problems conducted training courses for many Dow groups in many Dow locations in the United States and Canada. Concurrently ,with the development of the manual, the board or members of the board met one or two days a week with various groups needing help to deal with their problems. The philosophy of the board was that it. should be an advisory body and not a policing body; the responsiblity and account ability for the various materials, whether "they be wastes -13- or products was placed squarely on the shoulders of line supervision'. This advisory effort pioneered by company officials and expedited through ETAB has succeeded in instill- ing a high degree of awareness and concern by Dev; managers at all levels. It has resulted in a tremendous reduction in * the amount of undesirable materin-1s getting into the environment. : C ( I am relating all of this history and philosophy for one purpose-- to show that The Dow Chemical Company has been and is committed to the development of toxicological, industrial hygiene, environmental, and medical data that will permit it to successfully and profitably produce products that can be handled and used safely, be environmentally acceptable, and at the same time provide a safe place for its employees to work. Ill) Development and Use of Toxicological and Related. Data With more and more demands for information, the complexity of the problems of environmental hoalt.ii control increases. There are no simple, pat answers to the following questions: What is healthful? What is unhealthful? What is desirable? What is undesirable? We have much more knowledge today on which to base a reasonable judgment but we must be flexible to adjust to constantly changing' circumstances and constant!v advancing 1 now ledge. .. ... '15818 : that have been prescribed by various regulatory agencies to meet regulations under the Federal Hazardous Substances Act, *cthe Federal Insecticide, Fungicide and Hodenticide Act and others C Such studies are usually relatively simple and thoi'r purpose i" ' is to identify acute or short-term hazards associated with handling or use. When considering materials for uses such CD O cn as direct additives for food, .residues in food from agricultural practice, residues in food from processing procedures and drugs for long-term use, comprehensive toxico logical studies are required by the regulatory agencies. (EPA and FDA) I will not discuss the intricacies of a complex toxicological study but I can sketch a few principles to give you some notion of what is done today. The design of the study will be determined by the depth of the question (s) to be answered and may involve anywhere from one to several species of animals, from a few to hundreds of each species, a few weeks to years of treatment and observations and from a few hundred to several hundred thousands of dollars. First, wo must expose our animals in ways which arc pertinent to the manufacture, handling and use of the material in question. In an accidental spill, it may be splashed on the skin or in tiie eyes, or it may be breathed as an air dispersion. Also, 15819 -15- it may be inycstcd, ur.ually accidentally as in a case of mistaken identity. To evaluate the hazards of such situa tions, animals are given the material.orally in single or a few repeated graded doses, their eves and skin are exposed . . *.. t r . - .to various concentrations for'various periods of time. The results are useful in predicting the likely effect on humans from similar exposure. In the work area, the material may be encountered as an isolated event or a single exposure, or i't may be contacted repeatedly or continuously in fluctuating amounts during the 8-hour workday and a 5-day workweek for a working lifetime. As a general or public air pollutant,it may be contacted repeatedly or continuously in fluctuating amounts during a 24-hour day and a 7-day week for an indefinite period of time. If the material in question is likely to be encountered as a part of the air one breathes for an extended period of time, then animals are subjected to the material in the air they breathe. The amount in the air and pattern and duration of the exposure are selected to simulate real-life as well as exaggerated conditions. If the chemical is likely to find its way into food or potable water, it may be ingested daily for an indefinite period of time. Under such i \ . v v* :-: > v'l 58 2D -1G- conditions, its safety is evaluated by nutting it in the food or water of a colony of one or more species of animals for a lifetime or several generations. If a material is likely to be encountered by pregnant women/ it may be further - . -,,. - r . \ '# ' ' evaluated by administration to ='pregnant female animals during the gestational period to determine any effect on the embryo and fetus. The permutations and combinations are many and in order to answer the critical questions one must develop his experimental program with a knowledge of the properties of the substance and of the conditions of manufacturing and anticipated use. In discussing general approaches to toxicological problems, I have not dealt with specific observations that arc routinely made or that can be made if needed to answer specific questions. Perhaps a few comments to these points would be appropos. In all long-term or lifetime studies it is routine to follow growth and behavior, to do periodic blood counts and clinical chemistry determinations on blood and urine, to autopsy all dying or dead animals, weigh the major organs, and examine grossly and microscopically many tissues, usually 25 to 30 from each animal. The ultrastructure of individual cells as seen under the electron microscope is examined more and more freuuenlly even though the significance of subtle deviations - from ...normal are not .nlw.iys in Ler pre-table . " .J:,.'.r -17- Thc purpose of all these studies. is to detect any deviations between the treated and untreated animals. If deviations are found, they may suggest the need for special studies on those particular organs or tissues; thus the conduct of any comprehensive toxicological -.study -is subject to additions or deletions depending upon continuing observations and the need for additional data to explain how and why the material does;.:,what it does. Chemical analyses of tissues are frequently done to determine if residues of the test chemical per se or a metabolite(s) have accumulated in tissues during the course of treatment. ^ ' ^ c The primary, but not the only, objective of lifetime studies is to determine carcinogenicity and to relate this, if it is detected, to dosage. Mutagenicity, or the capacity of a material to induce genetic or inheritable changes, is of considerable concern today and will be henceforth. Animals on lifetime experiments can be studied cytogenetically for changes in their chromosomes in an effort to detect mutagenic potential. Other tests for mutagenicity such as the dominant lethal test or some variation of a host-mediated test, because of their singular nature, must bo carried out apart from lifetime studies. Auof*.c} pU- n..1o -r Ol toxic ity v;men m.ty or .'.'ey not be measured as a part of a lifetime* study is as assessment of reproductive ability. In such studies, the animals are permitted to reproduce through'three ejenerations while being subjected to the material under test. The re.suits reflect the stress of a particular dosage upon ability to conceive, gestata, deliver viable normal young, ancl nurse and raise the young. ( / / r*nn Teratological studies are widely used today to determine the capacity of materials to interior in one way or another with the intrauterine development of embryos and -fetuses. The test material is administered by an appropriate route to pregnant females, usually mice, "rats, hamsters or rabbits at varied dosage levels and at various times during pregnancy. The effects arc determined by examination of the fetuses taken by caesarean section the day prior to the normal delivery date and sometimes by examination of pups a week or more after natural delivery. Data from such studies are particularly useful in the evaluation of safety of drugs that may be taken by pregnant humans or on chemicals to which the expectant mother may be subjected in her employment or normal living. Another parameter of toxicity that is receiving considerable attention today is the effect of defined .md/ur control led sires:;*:-:} upon tiuv io '-, Jn:;.iL. or cond iLion *d. The results of such ' -- - 15823 1<J studios con sometimes do: waist- rat.- very subtle m.i: i>logic effects that would other1,:iso cjo undetected in cor. ention-i. toxicological studies. D O W 760578 As we proceed down the road from art to science, we arc becoming more and more cognisant of the importance of studying the metabolic and p h a r m a c o k i n e t i c _patterns of , v '' : ' materials. Such studies ca-n tell us how the intact animal body deals with a substance, and provide answers to such essential questions as: 1) What biochemical transformations of the material occur in the body and how arc these influenced by dosage? ' 2) How is the material excreted and how fast? 3) Docs it or a metabolite accumulate in the body? 4) Does the material interfere with a particular vital function of a biochemical nature? 5) What animal species is most like man in its mechanism for dealing with the substance? 6) Which species is the best for toxicological studies? As a part of any comprehensive toxicological evaluation, information relative to the pharmacological activity of the material should be obtained. Thin is usua 1.iv-done on -20- spccially treated animals or upon isoluted creran systems Such studies arc essential to understanding the node: of action of a material ar.d they arc a grocit. help to the physician who may he called upon to treat a case of C X C C S G i V C c xposure. . ...... - . / .*" Ti In essence, the objectives of a- tox icological study on animals are to describe the effects caused by various intensities of exposure measured in terms of the parameters of exposure , dosage, frequency, and duration. With such information in hand the toxicologic t can make predictions as to the safety of a particular situation if he knows the pattern and intensity of expected exposure. Here is whore the industrial hygienist comes in. It is his job to determine the .intensity and pattern of exposure to be anticipated in a r.cv; situation or in one that exists in an ongoing situation. With.both the toxicological data and the ind ustriai hyg ier.-,e data in himd, the physician, who is alway's in the picture, is in a position to make a better asscssmc nt of the her; 1th. cif the people involved. Ho- may even be able to improve on the medical surveillance program, and thereby gcnera te mo rc me a:ingful data . With all o the data derived from the three sources, toxicology, industrial hygiene and Medicine in hand, decisions such as the following can be Made: 1) it is safe to continue operations as they are; 2) Modifications must be made'in operations or e q u i p ment to reduce exposure; .. - 3) more toxicological, industrial hygiene and/or medical data are needed; 4) a continuous monitor of the work environment needs to be installed; or 5) go out of business. I have described briefly the 'closed-loop1 interactions of the toxicologist, the industrial hygienist and the industrial physician as we have practiced it for years at Dow. My experience tells me that the solving of problems r e l a t e d .to environmental health requires multidisciplinary cooperation not only between those professions mentioned above, but also between analytical specialists, design engineers, operating engineers, plan! superintendents, top management and most important, employees. % - 22- 0 O Vi 7G0581 Essentially, the same situation exists when the end use of products is considered. The toxicologist has been involved for years but in more and more situations the industrial hygienist is asked to go forth into the "field" whore products are used or wastes disposed-of* nnd measure the potential for y. ... exposure. For the most part, this is a nev; dimension for the industrial hygienist and even newer for the physician, but wo will see more and more of it in the future because such information is essential to the proper assessment of safety. As I am sure everyone can appreciate, all of these activities are expensive. Since resources in terms of man-power, laboratory facilities and money to pay for the work are always limited , we have to use-.our best judgment as to where we deploy our resources. In making such judgments,we have to consider the potential for exposure, the possibility that such exposure will occur and the-value of the ultimate product. If we are to proceed, an affirmative answer must Lc forthcoming to the question, can the product support the necessary research, construction, monitoring,and surveillance program? We have considered such questions as they relate to the subject of this hearing. The answers will be forthcoming as our case develops. * DOW 7,60582 IV) Thc Dove 1cprn-rnt o f Dow Toxi co] oc: ico 1 In format, ion or. 2,4,5-T and TCDD up to 1970 With this b ackground, I should like to trace for you the X- . % # 4 early v/ork we have condiicLed/on -2 f t ,,5-T anci TCDD and try to relate this with the sequence of events that have impinged so heavi ly upon the toxicology problems related to these co m pounds. - The compound, 2,4,5-trichiorophcnoxyncetic acid, (2,4,5-T) was evaluatee lay the Department of Defense at Fort Detrick during the early part of 'World 'War II and found to be an effective herbicide. Dow was awa**e of this and in 1545 2 , 4 , 5-T was subjected to limited toxicological studies. The con c l u sion from these studios were: 1) that 2 , 4 , 5-trichloropheno:-:yacetic acid has a moderate acute oral toxicity and is slightly irritating to the skin of rabbits; 2) that excessive exposure, to the dust of either the free acid or the salt would be likely to cause skin irritation; 3) that u-xpesure to dilute solutions, such as these used in practical application, would net be expected to cause trouble except among those v;ho persist in spraying themselves cr who do not take the necessary precautions to a-- i. i .Ll.i-ii.il i ' *;*.* I - -.'M r-'-r t : I -24- I I I I I I I 1 I I I I a a a a OOV/760583 p revent prolonged contact with the material; and *1) tnat reasonable handling precautions which will prevent ingestion and prolonged _ 'it' skin contact with the material should suffice"to prevent serious trouble. -f .\ A paper published in the botanical Gazette (June, 1946) revealed that 2,4,5-7 was cr.c of the more effective herbicidal materials discovered. There was little interest in 2,4,5-T until 1947 when Dow researchers found that it was a very effective herbicide for unwanted stands.of wild blackberry. .About the same time, Tam of Hawaii, reported it was highly herbicidal towards Lantana, a nuisance shrub infesting pastures. These two reports stimulated much work by agricultural research people interested in weed and brush control. * * In 1948, The Dow Chemical Company obtained registration of 2,4,5-T (June 10, 1948) (Rc-g. Ho. 464-069) for control of herbaceous and woody plants growing in rangeland, pastures, fence rows, farm lands and right-of-ways. hhen Dow elected to manufacture 2, 4 , 5-T, v;c were immediately concerned iv11 the possibility tlmt an imouritv could b^ present in the 2,4,5-erioklcrophonol used to make 2,4,5-T and tin: v. fnin m.i.guL cause cuic/racne problems. Our concern *"* > 15829" -25- D O W 7605&H stemmcd from the fact that in our research on the chlcrncno problem some years before we had learned that the waste tars from the manufacture of 2,4,5-trichlorophenol contained chloracnegcns. *v. ; .; * - ff . ** * As early as 194<1, Dow was using the rabbit ear test to monitor the waste oils from the 2,4,5-urichloiophenol process. The impurities were concentrated in these oils and v;c had learned that when the waste oils were low in acnegonic activity the impurities in the 2,4,5-trichlorophenol. were correspondingly low. Thus, when Dow became interested in inanufacturing 2,4,5-T in 194 8 we were sensitive to the potential for a chloracnc problem in the product. In 1949, we again conducted toxicological studios on our 2,4,5-T and there was r.o evidence of any- acnegonic response in the rabbit-ear test. The results of the skin application study was summarized as follows: "'When 2 , 4 , 5-trichlorcphcnoxy- acetic acid as a 101 solution in butyl carbitol acetate was applied repeatedly to the rabbit ear and bandaged repeatedly to the shaven abdomen, a slight simple irritation developed in both instances." During the r.e:<t few years, there was much toxicological work done on 2,4,5-T because of its wide utility" and general interest. The rather extensive literature to 1954 together with the results of work from our laboratory'' 15 8.3i D O W 760585 -20- to that elate which dealt with inyostior. were s u m m a r i z e d and published in 1954 in the American Journal of Veterinary Research, Vol. XV, No. 57,' Oct. .1954 , pp G22-629. The-article is entitled SUMMARY OF TOXICOLOGICAL INFOPJ1ATION-. CUi 2,4-D.AMD 2,4,5-T TYPE HERBICIDES AND AM EVALUATION' OF THE HAZARDS TO LIVESTOCK ASSOCIATED WITH THEIR USE b Y v - K - R o w o ' M *S * and T. A. Ilymas, D.V.M. The Summary and Conclusions were as follows: 1). The acute oral LD50 values for 2,4-b, 2,4,5-T and their various derivatives commonly used.in herbicidal preparations fall in the range of 300 to 1000 mg./kg for rats, mice, guinea pigs, and rabbits. Generally, dogs are more susceptible and chick:: are more tolerant of this type of material. On a weight basis, the toxicity to cattle appears to be quite similar to the toxicity to ordinary laboratory animals 2) The acute oral LD50 values for commercial formulations of 2,4-D and 2,4,5-T type materials are approximately proportional to -their content of active ingredient. The "'.inert ingredients" do not appear to contribute materially to the oral to xi city of the form,ulat icns . 3) Data availa bio indi cate 4e.lit 2,4 -D and 2,4, 5-T type her bici des inave a 1cw1 enroni c i t y . 4) MCP (2-motJ;y i- 4 -chi oroph e noxy <ace tic acid ) and silvox (2- (2 ,4,5 -tri eh le ror.-he:ioxy )prop ion ic nei d ) and the ir herbic idal dor x ve s a less tox ic than the corr ,w-jc.*>ir nc'ing r co be sii yh tly D an d 2 ,4,5-T type materials. 5) The hat ard to i ivcf teck arr; V/iddi ife assoc iat ed with the use as 2,4- , 2 ,AX,-r>,--Ti , reco If!w!ded or he rbi c.ides con ta in ir.{J NCI-, a nei sii vox is noy 3.ig i.hlc . It shou thes Id o b ma e rc tori cogn als ised can , he ::-C` c we ver, nta :ned thiar t a to xie n im a i s rumounts inive a o cu rj. to spray ttanks o r ot h e r cc n ta m e r r* of the materials 31V DOW 760586 I Early inforir.ation from the* FDA laboratories was not included I in this article so I shall summarize it in the following ' paragraph. I *Jt I In 1952, Dr. A.'J. Lehman, Chief of Division of Pharmacology of the U. S. Food and Drug Administration published Conclusions I from 30-week feeding studies done in their laboratories on 2,4,5-T. This information appears under the title "Chemicals I in Foods:A Report to the Association of Food and Drug Officials I on Current Developments. Part II. Pesticides. Section III. Subacute and Chronic Toxicity, published in Association of I Food and Drug Officials of the United States, Vol XVI, No. 2 April 1952, page 49. In a subsequent article in the same series "Section V, Pathology" published in October 1952, page 130, he states with respect to 2,4,5-T under the h e a d ing "Gross Effects", "5000 ppm not tolerated; no effect from 1000 ppm" and under "Histopathological Changes", "Negative. None of the characteristic hepatic cell changes seen with the chlorinated insecticides". During the ensuing several years, we had no appreciable trouble with chloracne so we just kept on doing what we wore doing. During this time, however, wo had several visitation.-: and inquiries from foreign manufacturers of 2,4 ,5-tr:chlorcpher.ol trying to learn why wo weren't having -s. *.. . I 158.12 8S09 Moa chloracne problems and they wert:. I am noL .sure that wo really knew except that they had had runaway reactions and we had not. In 1957, as a result of studies of the consequences of one of these episodes, Kimmi'g' and''Schulz' of. the University Clinic of Dermatology, Hamburg-Eppondorf, Germany disclosed in an article entitled "Occupational Chloracne caused by 7vronat:ic Cyclic Ethers published in D e r m a t o l o g i c u , 1 1 5 , 1957, pp 540-540 that 2,3, 6,7-tctrachlorodibenzcdioxin formed in the manufacture of 2,4,5-trichlorophenol was the likely cause of the chloracne in workmen making the chemical. (Later, a chanye in the numbering system for dibenzodioxin revised che 2,3,6,7designation to 2,3,7,0-). This discovery was subsequently confirmed by other groups of investigators studying outbreaks of chloracne in workers involved in runaway reactions in the manufacture of 2,4 ,.5-trichlorophenol. In 1964 , several Dow workers developed ck loracne and the bioassay program showed that the cliloracnc poton hial of the waste oil from the 2,4,5-trichlorcphouol procer; s had unkn ow in j1y built up to a danger point. Exposure to this war; te oil was the cause cf the acne in the workmen, not exposure to trichloropkor.ci . The plant was si:ut down immediately . Li on ss ays k DOW 760588 of Dow 2,4,5 - 1r ic;;Io rcp :: ;o1 u.v; 2 ,4,5 -'' :.g produced at that time were negati ve for a chlorarn'-g , hot i.e waste oil from Lhc production of 2 , 4 , 5--triehlorc phenol was very strongly acncgonic in the rabbit ear test. The prir.cipvil offending impurity was isolated and identified in '.he waste oil as 2,3,7,0 "tetrachlorodibonzo-p-dio;:.! a , TCDD. This confi'rr..ed the findings Of :K i m m i g :afid Sirhulv.. By early 1965, technology had progressed to the point where Dov; was success ful in developing a gas chromatographic* method for TCDD with a sensitivity of 1 ppm in 2,4,5-trichlorophunol and 2,4,5-T. (Sensitivity has since been imp. i markedly.) Vihen the difficulty was encountered in 1964 , Dow notified the Michigan Department of Health, the Institute of Industrial health, University of Michigan and various other health oriented individuals in private medicine and industry. In addition, Dow called a meeting of the other 2,4,5-T manufacturers in March, 1965 to describe the health hazard and share test procedures and analytical standards with them. The closing clown of our manufacts.: ring operation caused great concern among our customers, been a c 2 ,-i, >" I was. alre.idy in short supply. Dow elected to buy raw material with wnich to make its final products. However , we insisted that a specific tion be placed on any 2,4.,5-T or 2,4, 5 - trichlorophencvl purchar stipulating that neither could contain more than 1.0 ppm cf hh impurity, TCDD. We tested .sample's from ail potential supplier and found o n J v o:r.o who cor* id m e e t thc.-so. s j - c c f i i c n t i c n s i . 15834 "iim ;;:aIwu-ia 1 wo eded i mot:t our y, they received our business. that we assavid each carload of material we* Received and one carload wu.u returned to the supplier as unacceptable because it contained an excess of TCDD. .i.. '* ' > O 0 * -3 CT> O Cl CO cc Dow rebuilt its plant and brought it on stream.in 19C6 and since that time has had a self-imposed manufacturing specifica tion for 2,A ,5-trichlcicphenol and for 2,4,5-T. Trom 1905 to 1970, this specification was less than 1 ppm TCDD. This concentration did not cause a positive response in the rabbit ear tost, was the least amount that could be detected then by analytical methods available and was a level, which in our judgment, was .safe for use. As analytical technology has improved and manufacturing procedures have improved, specifica tions have been lowered.' F o r e x a m p l e , the specification with respect to TCDD in Dow 2,4,5-T was lowered from 1 ppm to 0.5 ppm. in 19 70 and to 0.1 ppm for the 2,4,5-T acid in February cf 1972 and for t h e esters in June of ]972 . On October 29, 19G9, Dr. Lee A. nuiiridgo, Science Advisor to the President ar.d Fncrucivo Secretary cf the President's Environmentai Ouality Council war. -informed of an unrclenscd report'.from, hi one tics Laboratory .that 2 , \ ,5-T was .teratogen io _and *this caused him to announce 'i.!.ut a "rcord inni.ed scriobV-. :h v;'y ; v:hr:h-hhym r *; . > -- _i JL -- . ... w .tt.. of actions arc being taker. by *U 1 i. m ios1- 1t #S*4<t -.*- f^* of the Government to restrict the use of the d-kiilincj chemical 2,4,5-T". The announcement continued 9* % ji J1L though'it seems improbable that any person could receive harmful amounts of tl:is chemical from any of the e x i s t i n g :uses of 2 , 4 , 5 - T 'and .while the relationships of these effects in laboratory, animals to effects in man are net.entirely clear at this time, the action, taken will assure safety of.the'-public.while further evidence is being sought".;-'f;; ; 4' , o <1 C5 O CH C5 O I The next day, October 3 0 , 1969, an article appeared in. the Washington Post and ether newspapers announcing "The White 1 House ordered restriction of the. herbicide 2,4,5-T," and reference was made to the B i o n e t i c s ' report. This news- 1 paper article was the first information most producers, I formulators and users received relative to the test results. t I Following the'Hu3ridee' announcement, The Dow Chemical Company, I as a producer of 2,4,5-T, becisme concerned about the quality p. of the material used 'in.'the Bionetics' study. '.This concern i-. 1 stermed from the knowledge that 2 , 4 ,5-T manufactured by some companies right contain several parts per million o f .... I the hignly tc;:ic contaminant 7 C D D . . In view of Dow's knowledge .1; V \u * I of the low mammalian toxicity cf Dew 2,4,5-7 and 'the absence cf reports o f .ino_*ease:l; incidence e birth defects in cattle I *-J,' - :*'ir>-o * .`S'. *'**i.#v/h'V -vO - S I ''<v.isv.`lv'V'-K-,*'.;*,*""*'--*V"**r; .-'*i* r.-; idol .:1 I...'' t: ?/** ( '''i'.-.V; D O W 760591 or shcop grazing rangelands sprayed with 2,4,5-T, Dev; found it difficult to believe that any practical hazard existed from the registered uses of 2,4,5-T. It was suspected that if the material tested contained excessive amounts of TCDD, this could be responsible for the observations. It, therefore, became important to learn of the quality of the 2,4,5-T _ { * **. tested and to gain additional evidcncc'^as soon as possible as to whether TCDD itself could bo responsible and would . 2,4,5-T meeting specification as made by Dow (<1 p p m TCDD) cause similar birth abnormalities. In order to expedite solving this problem, Dr. Dale Lindsay, Associate Com missioner for Science of FDA, was asked by Dow if a conference could be arranged with appropriate individuals in U. S. Dept, of Health Education and Welfare (HEW) and the National Cancer Institute (NCI) to discuss this problem and to develop protocols for tests designed to provide answers to our questions and concerns and which would bo acceptable to FDA and NCI scientists. Dr. Lindsay asked Dr. McLaughlin of the FDA to arrange a mooting which was held November 25, 1969. Present at this meeting wore Dr. I. Mitchell and Dr. ,R. bates ei NCI; Dr. J. McLaughlin, FDA; Dr. J. E. dohnnen, D. D . McCollister, Dr. V. E. Robinson and V. K. Rov.'i' .of Dow. Dew revealed to the Government people its knowledge of TCDD and its concern about the purity of '1 5 8 3 ? . ..-v f * .. I - 3 ;- the sample cf 2 , Dr. Mitchell was OO which bow could reexamine 2,4,5 - 7 and the suspected c o n t a m inant. Dr. Mitchell replied that teste with Sprague-- Dawley rats would Le the lest procedure for recon firmn tier, ar.d fur the*' CD o CcO? io stated that, for the purpose, it would be superior to a test with mice. i Dow offered to underwrite the cost of confirmatory experiments in the laboratories of the National Institute of Health, in the laboratories of a third party (independent of Government or Dow) or in the Dow laboratories open to observation at any V time by personnel of the Department of Hh'n. Dr. Mitchell .stated that he would have confidence in the work if it were done in Dow laboratories. bow aarced to repeat-the Bionctics' work with Spriteue-Daw 1ey rats using Dow 2,4,5-T of regular production grade. If this study yielded positive results the Hi emetics' results would be confirmed. If the results were negative it would be necessary to run further tests or. graded levels of eke contuminunr .ir.d or. refined 2,4,5-T. 11 w as ag reed th a t 1 ,w 1would : rovide samples of 2,4 ,5-7 a, . a ot < u fL > | f w v * * * w <. O ' * ^ ib u n c o c : : i r . to the t*l,U->*wion a 3 Institute of Ha virer,meut a 1 H-.} ;h be; en lunar '.tories -- 4. U . - . -- - -------------- - 15838,' .......__... ___ ...... II*!!* '.v.. *. > dw.-- . \ . * ' .* .* ~r ; ' T * . . . . . - *. <--. IV'Ti * tl- M' liW'.'-'*'* ( DOW 7G0593 - Ji - Research Triangle Park, North Carolina. Ifbinson nr.d Kowc cf bo: wore asked to vir.it the NJ V.llE labor a Ccri or: in order to confer with them concerning the details of the test methods to be used. On Deccr:JL>er 1, 1969, Dr. Johnson of Dow met with Dr. DuBridgo , ...... - , and Dr. Buckley of the OS'r\(,Office f Science and Technology} to apprise tho." of the possibility of a contaminant in the sample tested by Bior.etics and also of the information known to Dow. At this meeting, the plan for additional testing as discussed v/ith D m . McLauglin, Bates, and Mitchell also was. presented. Dr. DuBridgo stated that he would'be interested in further information as it developed and was willing to consider new evidence who., it was available. On December 11, 1969, Drs. V. B. Robinson and V. K. Rowe HiCt 'With brs . Falk, Co Park and discussed wit! study Lo be conducted i Agree me:'.t on the de;::g: and was ioilv'.'.'i::'; ir. th- -- -- .... 3! v'.-fc; .k -:*s4 ` -I; *** ' -- oia. ' 'vs r-.vd li.u'.  nn At this m e e t i n g ,Dr. Courtney of the *.*I Laboratory provided a 2 gm sample of the 2 ,*1,5-? used by the Diane tics Laboratory. This sample v:as examined at bow with the foil owing results: 1) Rabbit ear Lcsts shewed a strongly positive reaction characteristic of TCDD. 2) Analysis by gas liquid chromatography indicated the presence of 2^*3 ppm- of' TCDD (2 ,3,7 ,8-tctr&chlorc\ ' \ dibenzb-p-dioxin). c c On December 23, 1969, J. K. Johnson, Cl. E. Lynn and J. C. Hansen of Dow net with Secretary of Agriculture Ilardin and reviewed Dow's activity in the 2,4,5-T case. On December 29, 1969, Dr. E. H. Blair and others from Dow made a presentation to Dr. Burger and others of the Office of Science and Technology, relative to the chemistry, the Dew process for manufacture of 2,4,5-.!*,' and the methods used to control the levels of the contaminant TCDD. By January 32, 1970, enough progress had been made in the Dev: torato:cgicai study in rats with Dow production grade 2,4,5-T to nahe a report to Pr. Egeberg, Assistant Secretary for Health and Scientific Affairs, Dept, of H e a l t h ,Education and It- X1Xf14*.,1. Cop iek wt_`ri liV at to other inv IEh This .IVpc rL shewed that Dev; trio:rr-oi*3ie 2 , *.f r^,_rT> A W >4 ,4l4 ,**..use bir'h d-. f-v *' '** *' ^ ***' ..... "--c : | ;" T 1 ;-;V . . ' * - -V T `" .--`-re .' ' .w.ii- >--* *r 7'i:-.'.`-r; iQ A*. . 760595 * - J l.- by gross cxiirdnat icr. n: :clu:;os fro:/, pregnane rats fed 24 mg/kg/dny or. days C-I5 of gestation. The desage levels t *1? tnk Xi lIw. f was able to report to Dr. Egebcrc that a pilot study with pregnant o 0 rabbits fed the same Dow production grade 2 , 4 , 5-T had not caused birth defects. ^`he 1-ate Dr'.'Fi^- L^ Richardson,' Food and Drug Administration pathologist, was present and observed the fetuses taken by caesarean section from the rats in the studies just described. On February 17 and 18, 1970, the animals in our tcratological studies on TCDD were autopsic I and the fetuses examined in the presence of the late Dr. II. L. Richardson of the FDA and Dr. C.T.G. King of MCI. The results suggested that seme of the teratogenic effects reported in the Bionetics' study may well have been duo to the high contcntvof the impurity, TCDD, in the sample of 2,4,5-T which was studied. On February 24, 1970, V. K. Rowe presented a summary of our teratology studies to people from FDA and other concerned govemm.-.rv ai groups i:i W a s h i n g t o n . .^ 1584*-. -37- On Marcii 17, 1970, the final reporte of the Dow studier: were presented before the Society of Toxicology in Atlanta, CA, entitled TERATOGENIC STUDY OF 2 ,4 ,S-TRICIiLCROPiiENOXYACETIC ACID IN THE RAT by J. L. Emerson, D. J. Thompson, C. G. C o r b i y , and V. B. Robinson, The Dow Chemical Company, Zionsville, Indiana and STUDY OF TERATOGENICITY OF 2,3,7,8-TETRAC1ILORODIBENZO-p--DIOXIN IN THE jRAT b y 'G . 'L: 'Sparschu, F. L. Dunn, and V. K. Rowe, The Dow Chemical Company, Midland, Michigan. D 0 W G7 0 5 9 6 On April 17, 1970, J. E. Johnson, E. II. Blair, G. E. Lynn, and V. K. Rowe appeared before the Senate Committee on Commerce, Subcommittee on Energy, Natural Resources and Environment 1 chaired by Senator Hart of Michigan.' Dr. Johnson summarized 1 for the Committee the uses, benefits, and hazards associated with the herbicide. He paid special attention to the toxico 1 logical information available on 2,4,5-T and 2,3,7,8-tctra- I chlorodibonzo-p-dioxin, and told of the'work in progress. 1 During and since 1970, there have been a great number of toxicological and related studies conducted. Others from If Dow and elsewhere will be discussing these in detail in subsequent presentations. I VKR January 197C 1 I 15842" ' 1 a Dow Canada BflCHGROUTlDER L i Chemical Canada Inc. P.O. Box 1012, Sarnia. Ont. N7T7K7 June 30, 1982 Release no. p.nntarK- Don Stephenson 519-339-1599 Wayne Wolskl 51 9-339-1184 pnntrih.itnrc Dr. Richard Wilson- Harvard lln-lv. ____ (as reported In Weed Science Society _____ of America "Newsletter" October 1981) THE RISK IN SPRAYING 2,4,5-T HERBICIDE Environmental activist groups hav been demanding the ban of 2,4,5-T on the premise that it increases the risk of developing tumors. Dr. Richard WilBon, a Harvard scientist, disputes the 2,4,5-T and tumors theory, however, he recently calculated the risks associated with spraying 2,4,5-T and found that if a person worked at applying 2,4,5--T with a backpack sprayer for 5 days a w e k , 4 months a year for 30 years his/her chances of developing a tumor would be 0.4 per million. Those conditions would represent a probable exposure level far greater than the general populace, even if they lived in a spray zone. In comparison, other risks associated with developing a tumor are: Chances Per Million Sunbathing 5,000.0 Smoking cigarettes 1,200.0 Being in a room with a smoker 10.0 Drinking one can of diet soda with saccharln/day 10.0 Drinking milk with aflatoxin or eating four tablespoons of peanut butter/day 10.0 Drinking one can of beer/day 10.0 Eating 1/4 lb. charcoal broiled steak/week 0.4 30 - DOW CHEMICAL CANADA INC. N7T 7K7Modeland Road. P.O.Box 1012, Sarnia, Ontario, August 19, 1982 Mr. T. S. Thompson, Ph.D. Public Affairs Manager New Brunswick Electric Power Commission 527 King Street Fredericton, New Brunswick E3B 4X1 Dear Mr. Thompson: The attached letter and documents pertaining to the safety of phenoxy herbicides were sent yesterday to the enclosed list of Atlantic Provinces daily and weekly newspaper editors as well as two magazines covering the region. No broadcast media were covered because the complexity of the information does not lend itself to 60-second explanations. The letter of transmittal is self-explanatory. The point is that there is a great deal of scientific evidence attesting to the safety of these products and there is no Bubstance to alarmist claims. Please feel free to use the information enclosed in any appropriate manner. Extra copies of any item are available by calling my office in Sarnia (519-339-3131), our agricultural chemicals sales representative in our Halifax sales office (902-429-5623), or write to either location. We hope our initiative will lead to more balanced news coverage of the safety issue and result in a better informed public. Yours very truly, 'L / Harold W. Major Manager, Government Relations Agricultural Chemicals /kan 15844 -3gS> D O W C H E M I C A L C A N A D A INC. Modeland Road, P.O.Box 1012, Sarnia, Ontario, N7T 7K7 August 18, 1982 News Editor The Daily News 446 Main Highway Halifax, N.S. B4C 2S9 Dear Sir: Recently the phenoxy herbicides 2,4-D and 2,4,5-T have been "in the news" in the Atlantic Provinces because of allegations that their use for brush and weed control in forestry and on right-of-ways involves significant risk to human health and t h e e n vironment. These pressures have resuTted in some suspensions of proposed herbicide applications until "further study" can be undertaken, particularly in Nova Scotia. That has unfortunately strengthened some people's belief that the risk may indeed be real In view of the current controversy, we thought you might like to have information which summarizes what the world's scientific community knows about the health and environmental impact of these two herbicides. We also thought yod might e interested in knowing the relative risk that these compounds pose versti^ cither risks people readily accept. In actual fact, so much is known about the effect of these two herbicides after more than thirty year^ of research and use that it is reasonable to say they pose thousands of times less risk to human health than sunbathing, for example1 The herbicide most recently in question is Esteron*3-3E, a Dow product which, in its concentrated form before dilution for use, is 42 percent 2,4-D, 40 percent 2,4,5-T, a small amount of an emulsifier, and the rest light furnace ofl. This concentrate is diluted for actual spraying at ground level by mixing it with about 140 times its volume of water. This is a low volatile formulation which minimizes evaporation and drift. It isn't necessary for you to read all the information enclosed (just skim the summaries and conclusions sections) to gain an insight into the huge body of data that exists on the effects of 2,4-D and 2,4,5-T. Moreover, government-approved application rates embody an additional hundred-fold safety factor. % * Trademark of The Dow Chemical Company (more...) August 18( 1982 Page 2 If I can help you understand and Interpret all this science for your readers, please give me a call collect (519-339-3599) in Sarnia. Yours very truly, Director of Corporate Communications /kan Enclosures: (1) "The Risk In Spraying 2,4,5-T Herbicide" - Dr. Richard Wilson, Harvard University, as reported in Weed Science Society of America newsletter, October *81 Dow Canada Backgrounder #155, June *82. (2) "A Summary Of Pertinent 2,4-D Facts" - Backgrounder #159, Dow Canada, July '82 (supported by a bibliography of 134 literature references). (3) "The Phenoxy Herbicides, Second Edition" - Published by the Council for Agricultural Science and Technology, August '78 (Note Summary on pg. 1, para's. 4 & 5 ) . (Cites over 190 literature references). (4) "What 56 World-Renowned Scientists From Eight Nations Say About The Safety Of The Herbicide 2,4,5-T" - Backgrounder #160, Dow Canada, July '82 (based on the results of the June '79 three-day Dispute Resolution Conference On 2,4,5-T, Arlington, Virginia. Journalists can obtain a copy of thte complete 102-page report from Dow Canada). (5) "The Safety Of The Herbicides 2,4-D And 2,4,5-T" - Forestry Commission Bulletin #57, United Kingdom, 1977; by D.J. Turner, B.Sc., Ph.D. et al, (Cites 242 literature references). (Note Summary on pg.4 and conclusions on pgs. 39-41). (6) "On the Hatter of Dioxins In Our Environment" - Backgrounder #131, Dow Canada, December 1980. u 15848 RO BECO Er n s t & Yo u n g V - RESULTS FOR ALL CAUSES OF DEATH 22 Results of the analyses for all causes of death combined (i.e. total m ortality) are set out below, for the total cohort, and for two sub-groups of the total cohort, namely those with year first sprayed of 1959 or later and those with year first sprayed of 1958 or earlier. These two sub-groups were selected since there is evidence which suggests th a t diesel oil and used transform er oil was routinely mixed with the herbicide in 1959 and later years. If this is the case, these two sub groups would have been exposed to a different range and mix of toxic agents. Total Cohort The SMR for the total cohort, for all durations since first exposure to the herbicide, is 154 (Cl 126 to 188), based on 98 actual deaths versus 63.55 expected. The corresponding results broken down by durations since first exposure to the herbicide are set out in Table 1 below. jyO BECO / E r n s t & Yo u n g 23 D(Yu reaatriso)n 0- 4 5- 9 10-14 15-19 20-24 25-29 0-9 10-19 20-29 30 and over 25 and over 20 and over 15 and over All durations TABLE 1 ACTUAL AND EXPECTED DEATHS, FOR TOTAL COHORT, BY DURATION SINCE FIRST EXPOSURE _________ D eaths Actual Exnected 6 4.47 8 5.95 12 7.91 14 9.95 19 11.09 25 10.32 SMR Cl 134% 49% - 292% 134% 58% - 264% 152% 79% - 266% 141% 77% - 237% 171% 103% - 267% 242% 157% - 358% 14 10.42 134% 73% - 225% 26 17.86 146% 95% - 215% 44 21.41 206% 150% - 277% 14 13.86 101% 55% - 170% 39 24.18 161% 114% - 220% 58 35.27 164% 125% - 214% 72 45.22 159% 125%- 201% 98 63.55 154% 126% - 188% Therefore, for the total cohort, statistically significant excess m ortality is observed for all causes of death for all durations combined (SMR = 154, Cl 126 to 188), for durations 20 to 24 years (SMR = 171, Cl 103 to 267), 25 to 29 years (SMR = 242, Cl 157 to 385), 20 to 29 years (SMR = 206, Cl 150 to 277), 15 years and over (SMR = 159, C l 125 to 201), 20 years and over (SMR = 164, Cl 125 to 214) and 25 'ears and over (SMR = 161, Cl 114 to 220). 15848 I.., DOW-APPENDIX A PARTI THIS COM PLETES YOUR MARKED DOCUMENTS 1 9 -N o v --92 15848 Quik Print INSTANT PRINTING &PHOTO COPYING 98 Prince William Slreel. Saint John. N B. E ?L 2B3 (506) 634-8840 We can " Custom Print" Post-it" Notes C O A Q P A f i . . . ask our sales rep. lor details O O ^ r^ O U ^ rU 1585G DOW1 551475 .. r/.ib'J!o ity Inro# I t -'aa ! hr* eurpopo lecu.': 3 thi problm:! fo r/?a Lk 'r. 1 Liony hi> is-!viad tr.y or ic : n Ghe*.icnl ue t ht >.!:7h or. " r . k. Lie .-d v r r r l a r t i c l e a , Ji 1.. r:lgr t-of-vr.y3 :r cc.jrrjf* P .iv M 's p u b licity :rr:;Of tir* j -Umut ion, .~i poopla, r.t:i to or*'> tr y . " r . - "tf-y i.dvimd e l l prc;3`3 fit th at there was no ouch thine no k illin '' i*-b elts end they nuo.t bo Yrrong. Of course thiB sna the T/reng approach and r ig h t a way e l l of them f a i t th at probably the Power lino companies end t-ho e h ra ic a l ccmr.oniea were t-Tying to p u ll tha wool Over th e ir eyas. Sinoo 'V . Angst' s a r t i c l e s Ivav-o apenarod in vhe P o tta v llle paper, sene of tha n ation al sp o rt w rite rs have taken up Lno hue bi\X cry gg i t seorca to co quite :: nico co n tro v e rsia l subjr-ci fo r tb'v.n to gc-t In te l '1 ho w rite r observed several o;:chanroo of correspondence.' between the Katicnol ? r r-cionr.r of the Outdoor n r i t e r 3 A ssociation of Acnricen r.nd some of tV>< lc c n l sports clubs in the Pennsylvania area served by Ponna. p-ov/or and Light.. Inasmich no those v;riv.<r<3 do not know anything about chemical v:ocd centre.! r> ih^y huvn n.-.tuvslly a rum:.>3-.] t :u t a l l of the m aterials aro poisonous and ore thereby c re a tin '! c. so riru c hazard to lid l i f e of the carj-.unity, . As u r e s u lt of a recan t mooting the nbovs ninntionsd pucpln decided th a l they would turn th e ir problem ovor to ona fro fo o s cr fnyl.tsh of i'enuaylv-.nio 5tn to College who is apparently nn export on (5a'no v.ni<wl diaansor.# 'liny .ill rip-eel tc abide by Or. Fr e l i s h ' a recommcndatione During tha course- of our dlocuocicn it. w>o the w r ite r ' s ijsjroatlon th at o~rl; r-.; Dr. fngllah of Penn f t a t e and oneof the roprosantntlvo noc.barn of the outdoor w rite rs a sso cia tio n could bo in te re ste d -in taking v tr ip to our Midland, 'd ch iy m plant in ordor to observe tha to x ic o lo g ic a l lahcmutorios r.d the vnr.Ums procodur-' .- which wo go through to insure p o sitiv e s a fe ty for (.ho Ui:> of -Ivs c a t'-ria lu to our cv/n pvimounel end to people who are miin;* than;, Inasauch an Airorleun Cho-'dral faint, apparently do n et hr.vn too ituch toxloGlotflnnl 'tn fcrr.ation which they developed thnsoalvoa i t night. Ixv to Dov/' s udvnntuj.a t.o proas th is point, a t t.iiio tlr.io. I would approciate ronolving any conimonta f.het 'i*. law or " r . hmit.i) might, hiivo In t.ltio regard.. 1585U D0W ) 551397 y-' i .# {r i. M ID LAN D February 22, IS b l F. E. Cuollotto Lab e lin g and Product R o g u latin g S e c tio n 47 Building TCXICGLGGICAAL IITPORMATIOiJ ON A HUrlBER Gi? P R O D U C T S SUITABLE F O R APPLICATION FOR REGISTRATION IN MEW ZEALAND Hero I s tho In fo rm a tio n you wished f o r tho r e g is t r a t io n o f theoe prcductu In.Haw Zealand. I a h a ll g ive tho t o x ic it y d a ta ; the x'esfc you can g at fx*czn the l i t e r a t u r e I am eu ro . ^ -v] 'Jo co Vlddon D Vidden D has o moderate acu te o r a l t o x i c i t y ; tho LDg.Q v a lu e fo r rato ia 0.40 c/lcg with 10/20. confidence H a lt s 3 r 0 .3 1 to 0 .5 4 g/fcg. Eye co n ta c t t e a t s on r a b b it s ro o u lte d in marked p a in , moderate c o n ju n c tiv a l i r r i t a t i o n and tra n s ie n t co rn ea l i n j u r y ; h o a lin g o ccu rred w ith in two - th re e daya. Mo ap p re ciab le skin ir r it a t io n occurred in rabb it skin testa i f Vidden D vaa ap p lied so th at i t could evaporate norm ally. However, whon c o n fin e d , a a o d a rata i r r i t a t i o n cccuxTOd upon s e v e r a l houra c o n t a c t . Repeated prolongad co n ta ct *Jhen confined re s u lte d in a burn. In olein ab so rp tio n s tu d ie s rab b ito su rv iv e d 0 .4 g/ltg o f body w eig h t. Higher dosea wore not run because of tho severe burn produced a t both 0 .2 and 0 .4 g/lcg l e v e l s . When r a t s were exposed f o r one hour to 1 0 0 0 ppm o f Vidden D , one c f ten r a t a d ie d : aavsn o f tan d ied when e2cpoaad f o r two h o u rs. At 400 ppn (2 m g/l) both a two and ens hour exposure caused tho d eath o f on o f ten r a to . Signa of eye i r r i t a t i o n wero in m ad iate; d e f in it e in d ic a t io n s c f upper r e s p ir a t o r y i r r i t a t i o n and la c h r y s a t lo n appeared In about one hour. Human t e a t s In d ic a t e th a t th th re sh o ld o f odor f o r moat is; p ro b ab ly no g r e a t e r than th re e to f iv e ppm. A t e n t a t iv e th re sh o ld l i i a l t v a lu e f o r repeated d a ily 01 one pom I 30 been su g g e ite d , Fumaaone (l,2-dibromo~'j-chl iropropane) F u m a s o n a h a s a h i g h s c u t o o r a l t o x i c i t y ; t h o LDC ^ value f o r v a r io u s a p o o is a o f iir im a la ra n g e s fro m 0 .0 6 t o ^ O ^ l g /kg of b o d y weight w i t h o h i c .b a t h o rr.jrb t ;;uaespcible a n d s i l c o t h e m o s t r e s i s t a n t . Sy-s c o n t a c t testa on r a b b i t s r e u n i t e d I n m od o r a t o r.a ! n &r/J : . r i l d t r a n s i t o r y r c u n j u n c t i v a l I r r i t a t i o n . H a s l i n g c c c u r r i i n t w o t o t h iv s c d'.iys I n o le in c o n t a c t * 15853 wwi V 551398 :i: ft v .dt bi aa a cn ra b b r; a p e o ara ite v;a: :ana oauaa only a .uil.. irrittIon dhui. ' t , b u t i t o r .u to -'J a h u m r ;:i p r o l o n g e d ocnkr.cfc. Puanacra l a r e a d i l y a i - a o r l - h d c h r o u g h t h o e k l n . ; aiehiaghLtD.;:10 v a lia to r r a b b it a L o in ;; abouk 0 .5 s /k g ? body W: : oon i n h a l e d P i e a i e o n e \n a f o u n d t o b e h i g h I n hcL'icily te rato. cno icor, ;70 ppm; iic for r x ' r-rt v a l u e s a r e a p p r c u i i a i f c a l y ; '50, t;;owhcar3, 23-? p p i ; ; fe a r h o u r :;, fo r 15^ ppia j ara} tor o iht hour3,X0Q ppa. A uivon h o u r c a r j o a u r s t o 50 ppra c a u se d a a v a rL O o f f s e t s b u t th e iinisu ala r-s c o va ra d s lo w ly . Th o t e n t a t i v e t h r a a h G ld l i a i f c v a lu e c i'.g g O B tc d f o r r e p e a te d e x p o - s u r a uz P v n a s o n c l a b a l c w 1 p p *a . H irr.a n v o l u n t e e r s r e p o r t e d ti'Uifc . 1 . 7 p ? :s o f F u a -a x o n o w a s d a t o e t a b i c b u t n o t u n p l e a s a n t . (S e a e ls e d a ta h o o t e n t i t l e d " S u m a r 'y o f T o x i c o l e p i c a l I n f e r ior;t i c n a n d P r a c t i c a l C o n s i d e r a t i o n s i n t h e H a n d l i n g a n d U s e o f 1 , 2 -D i.b r c ? to 3 -C h lo ro p r o p s n o (P u fiQ a o rie )" . Zy tro n 3so Dcw C ra b G ra s s K illc -r in fo r m a tio n s h o o t a n t it le d " I n f o r n a tio n f o r R c Eo a rq h W orkars Dow C za b O ra a s K i l l r " . G a rle n G a r l n has a le u n c u to o r a l t o x i c i t y , th a L D ,; v a l t o f o r r a ta i s a p p r o x i m a t e l y U..0 g / k g o f b o d y w e i g h t . I t ,cW > f o u n d t o eau ce c z n y r .t i a l l y no e f f e c t when in c o n ta c t w ith th e t-yee o f r a b b its . In s k in te s ta on r a b b its . G a rl n caused w ild i r r i t a t i o n e n d s o s a a c s l i n a s o . I n fcha k i n t o o t s c o u d u c t o d , t h s r a w ere no syuptosrn o f a b s o r p tio n th z*c u g h th s s k in e b e o rv e d . Dows-on See d a ta sh a o td e n title d " T o x ic o lo g ic a l X n fo rc & tlo n R a le tiv s to Dwpcn o r R & dapcn" and "S im s a ry o f T o x la o lc g ie l In fo r? L a tio n , P r a c tic a l Cons id s ra tio n s in th e H a n d lin g and Use and F i r s t A id K s a a u ro s , D a ls p a n , S a lt". B a ron Soe d a ta sh e e ts e n title d "S u sa a ry o f T c x ie o lo g ie & l In fo r a tio n , P r a c t ic a l C o n s id r a tio n s i n H a n d lin g and ilea end P i r a t A id M caaurea" and " P ro p e rtie s , H a s ith H asards and P re c a u tio n s P e r S a fe H a n d lin g E & ro n ", K a ro n Por caci u'i'. l . t .iisC0 e n t i t l e d " S u n t r - s r y c f T o x i c o l o g i c a l Inferir i;ionr.r. j Fr?.o k1.-;::1 Co3iua'rstion-2 in the Handling and Une o* Kvcon, a Brut.:Vi K'lib:? i?oy^u'.ltio*Ja uni 'Yzvjpsrtios . H-c lia Ki . - /- V -.` w X .. U-V. h l i b i o .; * f o t * f o f v H a n l i g K u r t v a " . 15854 66STSS l ttOQ -.... ..v..... * *. !** *. 1 / . ^ < ' 1 - , i v f j ' 1 J J m i d u * 1 ") ^ . 4 - * u.J I ----* (- r ^ *A ' 4 .' . V -M ' 4 -a. A. J..-j *0 bj CJOi`X20d j i .C ' \ iAVJi cane dogr-aa lho toxicity Czi'irn en 1:2thyX C s\.fu a : ;.;* -2 l a a fs2 D a t o rd in a ry tcs:? c u lt u r e :;, fchsrufox*0 , fckcrj f.rj r.3 problem f r e a in g o s t ic n . D ir e c t f.-yc eento at w ith the liq u id has boon hewn fcc be c&pablo o f ?s.suiting in con iidoriblo e ic c c r .f o r t , tr a n s ito r y c o n ju n c tiv a l i r r it a t i o n a i.j co rr.ca l i n j u r y , b liin co n ta c t w ith t.vo lic n id ! r a y r e o u lt in a burn a a p a cia il'jr it* e c n fin o d .' The vcr.orn c f SotTfrasa MC- 2 a re vary i r r i t a t l r . r to the c /as, cau sin g Xachi^motion. 'fhay ar-o a liio h ig h ly t o jr ic . R a t s ' su rv iv e d a or.o hour expoouxe to 2CC0 cpra and an e ig h t horn* exposure to 2 6 0 ppm. R a b b its la vo been aheun to bo noro r e s i s t a n t than r a t s to* Dawteva MC-2 . Ac iiri Gviu'oupcsuro to c h lo r o p ic r in i s u a lik o b y , tha p r i n c ip a l h iz a r -1 i i 'on in h a la t io n o f BowfuES KC- 2 i s th a t p resented by e th y l b rcrild . The 'suggested th ra ch o ld veins? f o r repeated .p ro lc n tp i exposurea to its thy 1 bromide io 20 ppa. F o r 'hand ling p re c a u tio n s , asa fcho cnclosc-d b u lle t in e n t it le d "Bewfuen MI-2. " Di'^roa E3-15 Dowfuxe 123-15 has 3 sisdorato a cu ta o r a l t o x i c i t y ; tha ' IX-q v a lu ta f e r lab o ra to ry n im la range frcia 0.12 to 0.32 g/$g of tody weight. Eye contact w ith tha lia u id Kay re s u lt in . m odarats to eavo^o p a in ,.re o d sra to conJune;tivnl I r r i t a t i o n end w in c r ctrr.c-2.js. i n j u r y . H e alin g should fca reap l a be in s e v e r a l d a y s. A s in g le c h e r t s k in c o n ta c t should eci*39 no s o r e than r.*.incr i-rri:.at-i<'i'ij p rc lc n ro d o r fr e q u e n t ly rapoafcad exp osures such e.n way o c c u r t.1ten w earing cvnfcsininatGd o lo th isp scr shoo: way causa sa v e ro -p a in , b lis t e r in g and a bum . Bowfuns SB-15 i3 'nigh in a cu ta tc c c ie it y by e k in a b s o rp tio n ; tho LB- f o r . r a b b it s i s a p p r o j:ir a t e ly 0 .2 /i;g o f body m s g f r b . t H vapora c f Bo'.rfur.o E3-15 a r c h ig h in acu te t o x i c i t y ; the Lr ~ f o r r a t s I j 800 pp.u f o r ?. one hour exp o sure, 500 ppm fo^ua two hour exp&guvo. To,, ^uogcotcd thrbehold l i m i t v a lu e s f o r a in g ib twpoGiuec am as f o l le v s : 75 In O O FtJC pom fo r fo r fo r a 7 i hour o ;c c <* >* 1 h ';o r e ::p 4y 0 . 1 > -c u r ; mro 3so aibo tha enoiwssd reprint entitled,.'`"foxlaity Study of a Snot FumigCnt'\ 15855 DOW 1 551400 I it 75 t Lif vy . 1 -. i *,,;/. h .) vaino :........ 1, / V <. *-- J ^, If/;:./; usi/;he* Eyo *. a U4J. U ya -assc-i t'.s eapsbl'j of ' *,/ 'w<_/ a resulti;nj 1 blaN^_/ .r>>sb poiisa- , _ . ; \t i' --- ' ' - -- - _ .i. . _ - w* '_- i .siW*J. A al ah o r - u clrln oon- .,.. - '. ,. */ '' I : '" * * '-1 *at... /, .11; io. A > .V*C 1lycaci i;p iVctjuottiily -- ; ;j J *':'i .iit/ 1 ni u in a tua css soia! ly t'hcn * *' -, . *'"' tha main :i skin con-i ' * ?* \ n r , *<.1 4U V* 41-.-t w I - ; as :- sa/or/iPi-;:; through tiio a k in . ?rcr::or*ea io J . l -.hr."* t a ; la by t h i s y.iu tb j fchs Dr)1' i' o r ra b b lto towing in th& .-...e- o i# Z i j i-* i-rZA'Z c l1 bswSy Iu 3 l3 a n t ly Ppc- opco, : r:n i v a ./ .a a?. /,, a u n ts, ot a in s tb s s k in upc o o acact. f-; /ay cor; voiiivufcic;:} ci3 Fi-t,r.5rsa# d liu t o d w ith ;:a to r no cilrsa to d (i O crai eso ca /a b lo o* 'ca u sin g o n ly rcin sr cyo and s k in iu r it a b iu n . aui/vai, cash co seontrafclons naiy bo absorbed thi'ouci* t;:o e>:ir 'in t c ::io a s s u n ta . X hcpt* t h j a t ove l a h e lp f u l to you i n p re p a rin g tho in f o r m ation :n ;h;-:a pausante s u it a b le foi r c ^ io t u it io n puL^osoo in IIc-u . t s / i a c l . I f , h sv a v o r, you oncounfcor o - 3 d i* .c u lt y , l-r 1:2 ..*1 j *.*tJ r t.S / r.",. --t , A. /l'iv, ".U> EicokcnDCSi use :suuh Latocutoi'y 1 T C 1 S iU X .iir .g & l /u Euelciuiai 15858 1505 rL ,L. rz or o cji 'a h* tCC\JD3I ro 03 O' *tcr>i/icDc ou H djIc z z "2o j :7c:? ucvli to ovclu n to :z?otv of JL 3 rccCicCCo: ' r' ' cwc'y;c-c<' t~___. ^.Ly '-n: t3i eL ;iC i-O .i_ a * r- i_ .-y c _tt_-i_w0~sc-y~n_i^-*<I;nii__/._o-_ii~._:_i:"c ccwa.-?aCtiOCv. ot cc/.Corecionccncoio.-- ok\:i:' L 'w. t--- /o iCcCi'.cLjLC<LC.-:v/o3--*3ier"-~ n1-o l*-- --' -- C'2 cr<i^_-eT~Cn7t'v~*cftn^F ^ ( C--Gnwcb-0ae bt iivetrooe a*?^k^-> ec: LC: C .yLl'CC'lC?C'bVoCO cCCco3i e Crcr.P1oenCnLCizOnceC.c;tz: ;.tconLouoiretcsbcibct ioibcl ? r '-n odi o ua and n ti l Research 1J1 15857 Mill I ^ t ( Z 1 V 1509 A TALK GIVEN BY DR. DON D. IRISH IN BIOCHEMICAL RESEARCH DEPARTMENT CONFERENCE ROOM, 1701 BUILDING, ON JANUARY 18.1967 I am using many illustrations from Toxicology because I think they apply more in the toxicological area, of course. This is rough, and off-the-cuff. I did make some notes to keep me at least a little O Ox >foo ^<\> close to the facts and I'm going back further in history than the Biochemical area. H. H. Dow, who was the founder of company, (I didn't know him, I came here just after he died) was very interested in the biological area in spite of the fact that he was, I guess everything else from an elec trician, to a chemist, to an electrochemist, to whatever you want to call it. He got very interested in the agricultural area and grew a nice orchard out here; he used to take apples to national shows and win prizes. His interest, of course, affected The Dow Chemical Company slightly (as you would expect), and we got into the agricultural chemical business by making some old standby materials that have been known as long as there have been agricultural chemicals-- lead arsenate, Paris Green, and sulphur-- powdered sulphur. I doubt if many of you have ever even heard of Paris Green. It was a copper arsenical material. A fellow by the name of Kellogg, I don't remember which laboratory he occupied part of the time, I guess Chemical Engineering, was sort of a leg man for the agricultural area. He went into the Dow orchard and tried things out. Dr. Hale-- William J. Hale-- was an interesting person, as I discovered after I got here. He was also interested in the agricultural area. He started quite a commotion nationally by something he called the farm chemurgy, which means trying to interlock the chemical industry with the 15858 -2 - agricultural area by using the agricultural materials for chemical purposes and vice versa-- using chemicals in the agricultural area. (There's a national conference on the subject.) He was the Director of the Organic Research Laboratory up until somewhere around 1950. As he moved up to the front office, Edgar Britton moved in to be the Director of Organic Chemistry. Edgar Britton was also interested in the biological field, particularly the agricultural field. He had the notion of synthesizing nicotine or something close thereto. Nicotine was a very important contact insecticide in those days. Well, he gave up on nicotine, but he got into some quite unrelated organic structures, particularly the nitrophenols. They were tested at universities and had some activities of interest. There was also a group of relatively economic byproducts of our phenol process that had microbiological activities. That was another area of possibility here. Michigan State University microbiologists had tested these materials. (Didn't amount to much on the market in those days.) There was enough interest in this area that Edgar Britton of the Organic Laborato ,, suggested to a chap named Lindley Mills-- no longer here-- that they set up a small group to do a little work in this area in the Organic Laboratory. About 1931, Bill Allen, who is now Manager of Marketing in a byproducts area, came in. He largely worked in the agricultural area. And Bruce Fayerweather, down in the Patent Department, came in also as a microbiologist, from Michigan State. These people-- there are a couple more of them there but I thought-- you don't know them "*'vway-- they started the concept of what we call today TS&D-- Technical Service and Development. They'd take chemicals that -3 - were made in various places in The Dow Chemical Company and they'd r run out to the Agricultural Experiment Station at the University and I IJOfi have them tested and see if they could get Dow Sales to sell them. It was just sort of a "feeling beginning", if you wish. Then, in 1935 this group moved out of Research and into the Sales Department. They started what reall" is called today Tech. Service and Development. Now at an earlier date, in the early thirties sometime, Dr. Hale (Billy Hale as we called him) tried to convince Willard Dow that w i'J CD ought to have a Biochemistry outfit. Actually, why should we have a biochemist? I can only guess that he was thinking in terms of broadening the base, the disciplinary base of research at Dow. We had organic chemical engineers, physical chemists and physicists, and a few things of this sort. In any case, Willard Dow was receptive and started probing around. I met John Grebe about that time and John was looking around, so-- I was working for a drug company at that time-- it seemed sort of interesting, so we got together on the deal. That was in the spring of 1933. So, I managed to disconnect my former relationships and get here in August 1933. I came in, and I was taken to Willard Dow's office. Not knowing anything about The Dow Chemical Company or their interests, (not knowing anything more about biochemistry than I should, certainly) I said, "What am I supposed to do?" I think his answer was-- I believe an important basic thinking-- he said, "How do I know? I'm not a biochemist; you're the biochemist. You tell us. There's The Dow Chemical Company. If you can find a place for a biochemist, you're in." I think that's a fair statement of principle around The Dow Chemical Company. It 15860 -4- waa then; I think it still is to a degree except, of course, we're much larger and more complex. You're hired to use your brain. You're not just a pair of hands. You're expected to tell Dow Manage ment what is needed in your area. Management can accept it or not, as they please. There are a lot of other factors besides your part; you have to realize this, of course. But they need you to draw conclusions on your part. It's your job to know; to draw a definite conclusion; Management needs the facts and they need the conclusions, along with all the other factors they have to be concerned with, in drawing business conclusions. Well, I came in August. Where will we put a laboratory? We didn't know what we were going to do, we didn't know what we wanted. We looked out in this area-- and by the way, there was nothing this side of the railroad tracks at that time-- there was an old chicory plant out here (this is near where they grew chicory) and nothing else. The West Side Power House, which is an old place now, was a new building then and there was a little extra space out there. We looked at those and wondered how we could build a laboratory in either place. Then John Grebe suggested that he could squeeze a little space in the Physics Laboratory. Now, the Physical Research Laboratory then was occupying what had been the old garage and 48 Building is now the cafeteria. That was the entire area. So John squeezed out a little space for us in there. Well, at that time a general aspect of day-to-day operations in getting money and getting things, we turned to John as administrative head. Ray Boundy was assistant director there; Jack Chamberlin was also the administrative there, but he spent most of his time actually *O r./Ar.( i X -5 - working with Dowell problems and trying to cook up fancy electronic instruments for plant control operations. He was largely interested in that area. Willard Dow made it very clear, however, that he wanted a direct report from us on what we were doing and why. So frankly, I reported no closer to Willard Dow than anybody else. Well, we started out talking to people. What were the valuable fields in this great Dow Chemical Company? I didn't know anything about Dow. Might as well find out what people thought. Well, I got a lot of free advice, as you can expect, although I couldn't go into all the angles of it. Mills' group in the Organic Laboratory had already started to explore these areas. They were very anxious that we get into the agricultural field and microbiology field. Partly, because they were closer to the development-- to the Sales-- area, and they'd like to see more research, they'd like to see things coming into this area. Not to replace them, not with any transference with, but as a research backup. We could sit in many fields. Too many to mention-- I doubt if I could remember all of them. We took to human health, of course, animal health and nutrition, and heaven knows what else. I was in sort of an innocent mood one time after probing around and listening to people, and I suggested to Willard Dow that we didn't know enough about the problems of handling chemicals. Now you remember that things have changed. We used to make-- up until that time we'd been making old chemicals-- large quantities to go to large industries. Responsibility was not as great; fact is, we didn't know what we were doing ourselves. But now we had people 15882 -6 - synthesizing brand new things and I commented that I didn't think we knew enough how to handle the things and might get into difficulties. He came back with a very direct and very simple answer, "So why don't you do something about it?" That's quite typical of Willard Dow. Well that of course was the start of the idea, at least of toxicology. In fact, not many people did. Toxicology in those days was legal-medical toxicology and largely dealt with analyzing stomachs for arsenic and other jolly things like that. That's about all it was. Nobody conceived of toxicology in the sense that we do today. Now, of course, we shortly realized, when we got a look at this point of view that we had some concern for our own worker health, and that developed into what we call today "Industrial Hygiene" or "Environmental Research." Let us take a look at each one of these fields and follow the development. I'll take one of them and follow it through and go back to pick up the other. Get a feel for what we did and why. I'm going to use some anecdotes in here-- not because they relate specifically to those fields, that's their source, but largely because I think they give a broader picture of policy and thinking at that time, and I think you'll agree to that. We'll start with agriculture. They were slow in beginning; it's quite a sizeable field as you know. We worked very close with Bill Allen. Bill first came into the picture, of course, in the Organic Laboratory; he moved into the Sales Department later. And he was quite an important part of the development of the early agriculture area. Most of the work was done, at the time I came here, at the University's experiment M 15863 -7- stations by Mills or Allen contacting these people. Franklin Kagy, who's now in the Walnut Creek Laboratory, was at Ohio State University. He did quite a bit of testing for us at that time. Later moved into the California Division, where he was working with our Sales Department and developed the field station at Seal Beach. At the same time, Walter * t t Duck,a few of you may have known him personally, was at Michigan State University also doing some work for us. His work for us became so ^ dominant over university work that he moved out of the university and down to South Haven, and he set up an experiment station there in the field. tc GC Now these people reported to the Chemical Engineering Laboratory. You say, "Well, why?" Well, they were responsible for manufacture, sale-- in the sense of development-- of agricultural chemicals after they developed the procedure. Coming back to Midland. We felt, in discussing this thing, that we needed some backup in a more research sense in Midland, and they looked at us in Biochemical Research. Well, 1937, we picked up another biologist -- Fred Fletcher-- who went to the University of Syracuse-- professor there. In 1935, Lefty Lynn, who's now in bioproducts, had come with us from the University of Illinois. His work was not in agriculture at first; it was in microbiology and he did much of the microbiology of the early study of the phenol waste disposal area. By 1939 we figured we needed a more elaborate backup field research in Midland, and we got the farm out on Eastman Road and set up green houses, etc., out there. We got this going and moved in 1940. Lynn moved in as chemist, responsible for the development of these areas; and we sep up entomologists, plant pathologists, and agricultual people out there. Many of the older people in the present bioproducts, you will find, were in that group out there on Eastman Road farm. 15864 -8- Let me give you a couple illustrations of development in this area. But I want you to recognize these are more significant than just the agriculture field; they have a much broader significance, I should say. Edgar Britton had developed these electrophenols; one of them, di-nitro-secondary-butylphenol, was quiet interesting for the control of plant disease. It killed the fungus, it controlled the disease all right-- but it had a little tendency to kill the host plant, too. Now any intelligent plant pathologist would know that's the time to throw the whole thing out. But I want to point out I think there was some rather astute understanding that they took a look at it; it killed plants'. Now don't-- looking hindsight, looks real simple. Looking ahead is quite different. There were very few materials used at that time as herbicides to control plants. We didn't think that way. But I think it's very astute that there's a "It does what we don't want it to do, so how can we use what it does do?", and developed a pretty good herbicide that was used quite extensively. I know there was a lot of it used in California. I'll bring that up a little later as another illustration. The next one1-- a little more complex-- I think particularly interesting. In other words, this first one, when it doesn't do what you want it to do, what can you do with what it does do? It's about that simple. Another one, Dr. Hale-- Billy Hale-- had contact with a young Professor Watley down East. George Ehl (George is now director of Brooklyn Botanical Gardens) had done some very, very excellent research in the area of plant hormones, things that affect or control the growth of plants. It looked very interesting. He came in here as a l * * < 15865 - 9consultant and helped us enormously In our laboratory research to become familiar with these things. And we thought, "Now this has wonderful possibilities for the control of plant growth, increasing it, decreasing it, controlling it." And we even got quite enamored with pathenocopic fruit. You didn't have to pollinate the tomatoes, you could put on a little plant hormone-- we jokingly talked about a big ad in the Saturday Evening Post with a bi^j red tomato, underneath, "Fatherless tomatoes sired by Dow's Chemical." This was one of our jokes that carried over. But seriously, we were looking at this sort of thing. Here he was, -- and we were not as astute as we were in the case of the herbicide-- a university professor, I think down in Chicago, who suggested an entirely different purpose in other areas. Minute traces of these things were effective, but only a little more than minute traces were exceedingly effective in killing plants. Why didn't we see it? I don't know. But you can imagine when this opened up as a suggestion-- and by the way, he was a consultant to the government and this was thrown into the government area-- wide open-- you should have seen the scramble. We could spend all morning, fascinating discussion of the patent -problems and the chicanery and everything else that went on-- all over the country. The Dow Chemical Company came out on top. Why? Well, I have three angles that I want to outline. First: We had the field experience with herbicides, with that dinitrophenol complex, and others. We knew something about it-- we knew where it was needed, how to market it, and we knew how to use it in the field. Also, we had know-how in the laboratory on yxant hormones, not on herbicides-- we u U ii c'O fC Cl 15868 -10- understood the basis, we knew what they did. We knew what they did that we wouldn't want them to do. We had backup understanding. And third, the 2,4-D and the 2,4,5-T just played right into our rough product in our production area. We knew how to make it. Now, many people laughed, like they always do-- "You know how to make them? I don't buy that." We needed all three. But we did have this scientific know-how to approach this thing and have maintained our lead in the herbicidal field ever since. I brought this up because I think you should remember that sometimes, in a worthwhile field, you may not have to have complete patent control-- but it's nice to have. You may not -vi ('O ro CD have to have all the aspects of the thing, but if you understand what it's all about, when it breaks you're in a good position to do a good job of evaluating. Let's move on quickly. Julius Johnson came in 1941 to the Biochemical Laboratory, from Illinois, and we explored with him immediately the possibilities of the human health, area, the animal health area. That was right at the beginning of the war and there was a tremendous program-- as we were moving into tropical areas-- a tremendous program on malaria. We got very much involved in that. Julius was" doing the key work in our malaria program at that time. Well, Edgar Britton, of our Organic Laboratory, had become quite intrigued by the essential amino acids. It's an easy game to look back to see these things. They were brand new than. We'd just begun to know a little about them. He developed the means of synthesis of several important essential amino acids. Julius Johnson had done his graduate work with Rose in Illinois-- the very foundation of fundamental - 11research in essential amino acids. Well, Julius came to me one day and he said, "This fellow Britton has developed these things...I think we ought to do something with them." I said, "Fine. What do you want to do?" He said, "I think we ought to look at animal nutrition." "Swell. Let's go." It was immediately after the war; the malaria program went down. We moved out to what is called "the old bromine plant," at the end of Main Street, in that area which is now occupied by Northwbod Institute. It was an old dump, I'll admit. But it was an economic way of moving into the animal field, out away from the rest of town, to see what we could do. So,we developed the second farm-- this for animal investigation. Heavily into the chicken area and chicken nutrition, but other animal nutrition, too. And I think this was the foundation of our methionine business and a number of other things, but I won't go into them. It was a break into this field of animal nutrition. Now, Dow had grown pretty large by then relative to the small company it was when I came here. And to handle all the chemicals-- plastics, agricultual chemicals, metals, what not-- all in one pot, it was an extraordinary difficult thing. It needed sharp delineation of a field and what it was. Willard Dow had started this idea of setting up product departments. The obligation of knowing a field, knowing what was needed in the field, and serving that field. Well, several of us who were concerned in the agricultural area were pushing very hard that we did set up such a department in the agricultural area. Bill Britton, who was then in charge of the pilot plant area, organic chemicals basically, was put in charge of this group. Mills, who was in biochemistry, 15868 -12- pushed Bill very hard, saying "If you're going to be successful, you have got to move this research into your product department." Now that was not the way things were set up. I think we can say that the Biochemical Laboratory was very inclined to promote this thing and to give up our prerogatives there in order that this be well done, and I think it was. We reorganized this, and moved it there, and Julius Johnson took the position of Director of Research in the agricultural area. Of course this has grown, as you know, into the present Bioproducts Department. Well. Let's return to 1933 and take a look at microbiology, as time moves. This moved more rapidly than did the agricultural research. It's a bit simpler, you know. The bugs are smaller, and It doesn't take quite as big a field to herd them, and the apparatus is a bit simpler. So we moved in the field, I think, more rapidly for that reason. We had this small group of compounds, we called it Dowicides; we knew they were active in the microbiological field, but we didn't sell many of them. An energetic young chap by the name of Don Ballman came in. You probably know Don now as one of the vice-presidents in the Marketing area. An executive and on the Board of Directors. Don was an energetic young fellow then, and I wonder sometimes if it wasn't a little waggish point of view on the part of our Executive Sales to say they quieted him down by giving him sort of a working post. And, they dumped in these Dowicides. I've got to hand it to Dow, he made something of it and in no uncertain terms. I want to give him a lot of credit for it. About that same time, about 1935-- Don came in 1933, the same time Biochem started-- by '35 Mills' group had moved into the Sales Department, Technical Service and Development. Bruce Fayerweather moved to Patent md DOW1 277289 -1 3 - Department. The whole matter of research, development, sales service, microbiology, everything else, dumped into biochemistry-- we had the whole works. Working closely with Don Ballman in the Sales we, I think, succeeded in going places. Now, as this thing moved, there was a young chap out in Nebraska teaching out there in a medical school-- by the name of Edwin Dunn. We captured him and brought him here because we felt that with his broad background in biochemistry, particularly in the enzyme field, he might do something in this microbiology field. Which he did. Primarily because we were interested in preservation again, toying with the area of fermentation (I'll mention a little later), but also we wanted to do some basic biochemical research in the field of enzymes, and this was in the area that he graduated. We were just going with this business of preservatives field when The Dow Chemical Company acquired a wood displacion plant in Marquette, Michigan (acquired the Cleveland Cliffs Iron Company) became the CliffsDow Company. Edgar Britton and Willard Dow were very interested in the possibility of converting this cheap wood waste, sawdust, everything else, into sugar and alcohol. Alcohol is a very fundamental chemical raw product and we could get it cheaper. Bill Britton, then in charge of the pilot plant-- organic pilot plant-- started to set up the pilot plant for fermenting this. Not fermenting-- hydrolyzing th9is wood to sugar, to a sugar solution. And the Biochemical Laboratory took on the job of trying to ferment the resulting mess to produce some kind of a chemical. Ethanol was one that they particularly wanted, but we also looked at propionic acid as an important product at the time and also 15870 BOW1 277230 -1 4 - something we could fool with here. Some very intriguing scientific aspects of this thing, but I won't take time to go into it. I'd say that it was reasonably successful as a new technical angle. However, the economics of the United States at that time-- in the thirties-- was not particularly exciting. Black strap molasses in waste materials from the sugar industry was very, very cheap. Mostly sucrose but it was fructose, pentose and maltose. So the total picture economically did not look good, so we dropped it. Well, many people have come and gone in microbiology; many things have been done, and I can't take the time to go into them and I don't think it's important. You can get them from Paul Wolf who's been around here. Paul was one of my fellows that was here (not at the beginning, but came into the act when it was early and been here ever since) and made a major contribution, particularly to the preservatives field. But there's one area in microbiology that I must mention. We found that pentachlorophenol was a very good wood preservative. Wood rots, got a bad habit of that. And this was an excellent market, and in order to effectively develop this thing we got a group of people who knew wood technology and the wood problem, and as a result we got interested in wood. Interested in wood? Why don't we look at other aspects-- it not only rots, the stuff shrinks and swells and bugs eat it, and it burns, and things of this sort. How could we chemically change this thing, which was an economic, light weight, decorative, structural material. This really is the basis of the wood group which split off from the microbiology to put most of their effort into the development of wood and wood products. Fred Meier is familiar with that. Well, let's go back again. Please understand I'm sketching these 15871 -1 5 - thlngs pretty fast. I'm going to cover a third of a century in a few minutes. I want to go back to discuss toxicology and environmental research. And, as I promised, I'm going to cut down a lot of this discussion; however, I think there are some very important anecdotes in the development of this that imply much more than toxicology; apply broadly to policy and thinking. e You remember that I had suggested to Willard Dow that we didn't know enough about our chemicals toxicologically, and he said, "Why don't you do something about it?" Well, I was pretty naive to that suggestion, I want to tell you. I thought we had to know something about the new ones. What I didn't know was that we didn't know very much about the old ones. But leave it at that. Toxicology and Environmental Research were new to the industry; I mean that literally. I would look back and think, "Oh those horrible people," and how cruel they were. Bill Britton commented that he came to work at The Dow Chemical Company in the mid-twenties and there was no chemical industry in the United States, and he was just about right. There was certain, nothing that amounted to anything in the chemical industry prior to the First World War. Just really be ginning in the 1930's. What did we make? Phenol, caustic, chlorine-- old, old, old chemicals. We made them in carload lots; we sold them to major chemical companies. We had every assumption-- they had every reason to know as much or more about them as we did. Why should we do toxicological work and environmental research in this product thinking? However, things were changing arJ changing very rapidly. As billy Hale came into the act, now, only at first to develop processes for old chemicals; but then we began to make new ones. Edgar Britton and his gang, and Clarence Boyle was with us, were starting to look at new things, entirely new. -16So lit time there was a real revolution in the chemical industry. Don't forget, and this was part of it. Well, we started in a single room in 48 Building, which was the old garage. In order to get an animal out, we pulled a construction shanty up outside where you could climb through the window to get to it easily rather than having to go around to it if you were in a real hurry. We made a comfortable little animal house out of it. The first chamber we used for exposing animals to gas vapors, etc., was a 55-gallon drum; they called it a quick closing drum. You slapped the head on and clamped a metal clamp down, like that. Unclamp it, pull it off again. And it was very handy. We had them out there in the warehouse and just went over and swiped one and brought it over to the laboratory. Good apparatus. I might comment that the first toxicological investigation, and I confess, extraordinarily crude, on 1.1.1-trichloroethane, known as methyl chloroform, was performed in that drum. And it's still quite surprising. We even carried the animals up to anesthesia day after day after day and they seemed to get along fine. We brought it up again after we had a little better apparatus and a little better means of doing it. _____ . Now I might say the first experiments in the field of toxicology were animals. It created more amusement around The Dow Chemical Company than it did serious consideration. We were quite the laughing stock, for certain, in a good natured sense, I agree. Until something serious happened. This was in early 1934, I think in the spring, or early summer. I came to work on a Friday morning and Dutch Beutel was sitting on my desk. If any of you knew Dutch Beutel, you'd understand this. Dutch is a t Z Z L l . 7 . I MM -1 7 - chemical engineer, short, stocky, jaw sticking out-- swell guy. He moved on...he was then assistant manager at Midland...Willard Dow's assistant. He moved on to develop the Texas plant. He is now in charge of our Government Affairs Department; has been around a long time. Well, I blinked when I saw Dutch sitting on my desk. He said, "I hear you've been tinkering with a bunch of animals. "Well," he said, "show me what you can do. A man died out in the butylphenol plant last night and we suspect some chemical exposure. Get going." Just like that. That was his way of approcach and I respected him. So we did get going, believe me. We worked day and night, and week ends, through that week-end. And I might comment Mark Putnam, who was then director of that production division, moved into the laboratory. I think it was typical of The Dow Chemical Company in those days, I think typical today, that their point-of-view was that this kind of accident should not occur. Period. There wasn't any question about it, this wasn't something that you accepted. Now Mark Putnam was not in the way; he was not that sort of person. He was there to be used. He brought Bill Williams in. Bill was in charge of a particular plant area and later was placed in as production manager. Those people were available to me on a moment's notice, day or night, any chemistry in the process. I went into the plant with Bill Williams and we got samples all over the place. This sort of approach. That's the sort of backup we had. We sent dow drivers all over the state picking up odd animals for us in a whale of hurry, too, because we didn't have enough. Well, that's quite a bit of a story. But, to end up, we discovered that it was not butylphenol but... and it was not a strange, new and startling thing...by absorption through the skin. I wish I had time to go into the actual accident because it's quite fascinating to recognize how DOW 1 277234 -1 8 - people can know something and still not know it. But let's skip it. I went to Willard Dow. I said, "Now we know what caused it. What more do you need to know-- The Dow Chemical Company?" Well, I can almost quote him saying, "Get the information that you need to see that this king of an accident does not occur again in The Dow Chemical Company." He didn't mean phenol. He meant any chemical and he meant it! If you knew Willard Dow, you'd know he meant it. "Well", he said, "get the equipment, get the people to do this job". Well, that gave me a good excuse and I sneaked down and grabbed Ed Adams and dragged him in in 1934. This accident, I think, tells us quite a bit about Willard Dow and I think about The Dow Chemical Company. And I think it's still true today. Well, another session a good many years later-- I think I must slip in here-- it concerns our safety program. Willard Dow didn't like the safety record then. He couldn't figure out why people wanted to hur themselves. He began to suspect that line management didn't believe that Executive Management wanted the operations to be safe; they though they wanted production turned out in spite of anything. He wrote a letter...I wish I had a copy of it-- I probably could get it easy enough-- it said to all Executive Management and I can summarize it...it said in no uncertain and blunt terms, "If you plant can't be run safely, it won't be run, period." And He meant it. At that time also he established what was called, the Executive Safety Council. And I want to illustrate a point here by...he called Dr. Strosacker. Dr. Strosacker was a vice president and he was in charge of one of the large areas of production. A very able man; an awfully nice person. Dow said, "Tell you what I'm going to do" and Stro said, "Gee, that's wonderful-- I think that's a marvelous idea. I've got just the man in win | 2 7 7 2 3 .i 19' my division to represent us." And Willard Dow said, "No he won't. You will direct this. Stro, you're going to be on that Executive Safety Council. I want Management, my management, to know that Executive Management means what it's talking about." And I might say that the chairman of that Executive Safety Council was the vice president and general manager, Mark Putnam. And I might say,- also, the plant super intendent who had to show up to that executive meeting and report every accident, and one thing they had to tell them is how...what they had done, and how they would prevent this from every happening again... there wasn't any yes or now about it. And I might say they did not like to show up a second time either, particularly. Well, back to toxicology and biochemistry. That butylphenol accident, way back in '34 taught us that you need not only to have information, but you needed to convert that into a language useful to a man in the plant. You had to know what was going on in the plant and how they operate. So we got ourselves entangled with that situation and this, of course, is when we woke up to the fact that we had to do something in the area, and it became Industrial Hygiene and Environmental Research. Nobody knew about industrial hygiene then, shall we say, but we found out about it in a backhanded way. There weren't many people in the country who knew much about it in those days. We found that we had to define the actual environmental circumstances and Ed Adams did much in the evolution...in the beginning of these things. There weren't any texbooks, no simple rules, no real body of previous knowledge in the area; very little equipment. We had to improvise about everything we needed. There were a few standards. Not enough to hid behind. Or-* -2 0 - It was necessary to take the full responsibility yourself, in drawing conclusions...all by yourself. You didn't have much in the way of technical knowledge or backup. Now line supervision did not necessarily welcome us with open arms, as you might understand. They were a bit afraid we might find something that reflected on the quality of their operation. Now, let's be reasonable and human-- they were very human. Very ordinary. Don't forget that times were changing. I thought maybe some people didn't care about human life out there, but I find quite the contrary. And I found some men who did run their plants and ran them well. It's when something changes, when something new comes into the picture that we had a real problem. Well, it took a long history of selling that to plant supervision, I assure you. About that time Willard Dow got very interested in this and he asked me, he said, "Do you want policing power in the plant?" In other words, the power to close down a plant if something goes wrong. And I said, "No!" And I'm awafully glad I did. The supervisor, if he found he could dump his responsbility on us, would be most delighted. And we did not have the men to be in constant surveillance of every action in the entire plant, I assure you. We figured that it was necessary for that plant supervisor to -remain captain of his ship and be fully responsible. We were his technical advisors and assistants. I think Willard Dow wanted exactly that aspect, but he wanted us to come to that conclusion. It made it a little s$ow in development, but I think much, sounder, much stronger, and I think it stands up much better today, don't you Harold? Well I'm going to skip quite a bunch of stuff in here. There's some very fascinating cases in Toxicology that do have a lot of implication but I'm going to jump over them or I won't get done in time for lunch. 15627 -2 1 - Oh, yes. The solvent field. Now this is a bit toxicology, but I want to bring it out because of its importance today to get a feel for how we get into things scientifically. The Dow Chemical Company had all the backup and raw products and know-how of making a lot of chlorinated hydrocarbons. Of course, we make carbon tetrachloride, trichloroethylene, perchloroethylene, ethylene dichloride, methylene chloride...well, you name it. Anything that was of any use in the field we were in a position to make. Carbon tetrachloride, in those days, was available anywhere, in a drug store, a hardware store. You could take an old can or a pop bottle and go down and get it anyplace...you'd find it in every backyard. I was going to say garage, but also the stable because we didn't all have garages in those days. You people wouldn't understand that. There were other means of transportation besides automobiles. In fact, you would cringe with horror if you were familiar with the amount of misuse of this material. Small drycleaning establishments used it...they did not have the equipment, they did not have the know how ...to handle it intelligently. Now, why did they get by with it? Well, there were several reasons, as you people in Toxicology well know, in the phenol area. An individual can tolerate...most individuals can tolerate...a surprisingly large amount of this material for at least a reasonably short exposure. Even continuous exposure, in use, didn't cause obvious difficulties. At least they didn't spot the difficulties in the early days. Partly tremendous individual differences, I must admit. Now. I've known some people...I still know some people-- I mean they're still alive today-- who have literally wallowed that stuff. I don't know how they did it...I frankly don't. I suggested to one of them that 1587 -2 3 - couldn't quite understand what in the world all of this stuff was all about, I said, "Would you mind donating your liver and kidneys, when you die, to scientific interests?" He looked a little peculiar when I said that, and said "I'm not so sure they're what they ought to be." But they were beginning to identify some of the cases, not only the acute problems, I could tell you some instances that occurred during the war and in the early 1930's. . . 1940's, I mean, positively staggering. You could not believe them. In the early '30's this was beginning to stir a bit in the industry, and Henry Fielding Smith, Sr., father of the r RPyf f man we know at Mellon Institute as Henry Smith, did some animal work. He came around to various industries and' studied people, and I want to tell you that this work was quite an innovation in its day. He told us a lot about this material and what it could do...came up with a suggestion that we ought to have control over its operation within about 100 ppm concentration. We know today that's rather high but don't forget the perspective the day in which that work was done. I think actually, if the industry hadn't really, and vigorously stuck to this 100 ppm that a lot more live people today . . . and they operated in much better circumstances than they did. The heat was still on carbon tet. We felt the picture was by no means clear and we decided to take a look at this material and several others in their class which I jokingly called the "big four": carbon tet, trichloroethylene, perchloroethylene, ethylene- dichloride. We originally took ethylene chloride and started to work on it but people at the National Institute of Health had started to work and we knew them well and we said "Well, we'll swap with you". As why should we both do it. Well, I jump over all this rather elaborate investigation, I think actually almost classic in its day. This work has been quoted and respected nationally and internationally. We decided that carbon 15879 -2 4 - tetrachloride must be controlled below a level of 25 ppm and below a time-weighted average of 10 ppm. And I think that after a good many years we can say this was a well justified suggestion. However, (now I see where I got beyond toxicology) we recognized that this meant the death of carbon tetrachloride as a pocket solvent-- as a miscellaneous material kicking around. Well, could you convince people all over the country, all over the world-- distributors and handlers, that this meant the death of a t solvent they'd used for years? Generations of people had used the stuff. Now you couldn't convince them easily, I assure you. At the same time we were studying these other materials we decidedly got interested in the differential of action quantitively and qualitively of differently chlorinated hydrocarbon materials we picked up on the materials we had as an intermediate that they called methyl chlorofrom-- 1,1,1,trichloroethylene. Well, believe me, in deciding a relation to other materials we were utterly astounded because it was so low in toxicity. It didn't make any sense at all at that time. We know more about it today, of course. At that point in time, very close to carbon tet-- an extra solvent. We said, "Oh, boy. Somebody's going to run us out of business in carbon tet-- let's put another solvent together." Well, do you think you could convince sales people, our distributors, that carbon tetrachloride was dead? Not easily. But, could you convince them that anybody would pay for a thing because it was a little safer, and they said "No" and I think maybe they were right, then. However, looking back it lo''1-.r, very simple, looking ahead it did not look as simple. I couldn't go into all the contributions of many - T V- different laboratories. There's a lot of aspects in getting a solvent on the market-- net just toxicity, believe me. This stuff wasn't ^ 15-880 O h * f -t > I -2 5 - inhibited; it reacted on aluminum and heaven knows what else-- well, your know the story. It wasn't an easy task but today, as I think you all know, it's a pretty sweet product. Now, I have a moral-- it's much more than toxicology-- don't weep over a dead horse, get another one to ride. I think that's a good sound basis, industrially and scientifically. Well, I've had a long story; it was too long. I want to move on. I want to get in a couple more sermons here. Field of education. Yes, we need to get the facts, but that's not enough. We need to integrate them; need to interpret them, put them in plain language. You must see that the people who need to know, understand it. I don't mean to say that you give it to them. You have to know that they understand it. That means plant supervision, that means workmen, that means customers, general public, anybody that needs to know. Well, skip along to other areas here to get going. Publication is another sermon I want to make. Let's go back to ancient history again. Back in the very late '30's we had developed some very interesting scientific research. I went to Willard Dow and asked him what the publication policy should be on this kind of material. This was entirely new to Dow. Pertty new to the industry, really. Now I'm going to confess, I gave him a sales talk. Alarming approach. And with a twinkle in his eye, he chuckled just a little bit and he said, "Well, I'm quite sure" (and he named a few companies-- by the way, he was sure right), "will ride on our work," and they did. But he said, "I still think it ought to be out." Then he made a qualification that I want to emphasize to you and I'll repeat it every day if necessary, one qualification: "Know what you're talking about before you publish it." That's a pretty darn good one to look at; and if you'll look at the published literature today, you'll see why. It isn't the pages; it's publication that's important. mm j 4 -2 6 - I'cTlike to add some factors to this that's an addition, but I mean it's an interpretation of the same thing. We don't publish just to publish. We have to be sound scientifically. It has to make a genuine scientific contribution. I think, on the whole, this laboratory has done that, and I think for that reason it has been respected nationally and internationally. It is, wherever you go. I think at the same time, something you can't put your finger on, or can we? We have saved a good many lives. I think we've prevented a good deal of illness. I'm not talking about our own people only. I'm talking about the fact that this information was out and around the world in various places. I think also, that it's been a great deal of value to The Dow Chemical Company in the promotion and development of its products. And now, I've neglected one of our very important areas-- if it is an area; I'm not so sure it is-- and you'd like to call it basic research. It's important, perhaps because it's not an area. I think that's one of our sad errors. It's not something isolated over here somewhere in an ivory tower. It's important because it impinges on all areas, and be cause it is an integral part of all areas, and because it contributes to all these areas. I think that is the Important part of basic research. It's not easy to demonstrate basic research by the same kind of anecdotes-- I won't take the time anyway. But let's go back and take a little look at the history as I think of this era. Ed Dunn came here in '34 and we were thinking of the Dowlcldes pretty serious. But frankly, we were thinking also of the fact that Ed Dunn's graduate work was in enzyme research. I proposed to Willard Dow we ought to look at enzymes as a basic research program. He grinned and he said, "You mean organic catalysts?" and I said, "If you want to call them that," and he just chuckled and said, "Why don't we get going?" Well, Ed Dunn did do something-- did some v-iry interesting work in ?,h?f t -27- this area; however, unfortunately, as too often happens, (watch this), the immediate pressures of preservatives, fermentation, and heaven knows what else, dominated the picture, and this went down hill as a basic research area. It was displaced. However, let's see, it was about 1957 we discovered an innocent chap, a good Canadian boy with a bit of experience in England and some other places, by the name of W. Brock Neely-- some of you have heard of him. And we managed to get him here in '57 and suggested that he go into this basic biochemical research, particularly the enzyme field-- not limited to it by any means, as you know. I won't go into any other areas because you know many of any other areas in which these have been explored. He stayed with it. Not exclusively, but he stayed with the basic area. Remember we mentioned that one of our earliest considerations of the many things were exploring was human health area. We hadn't done anything about it. We kept probing-- what'll we do next? In 1953, we managed to get our hands on an innocent guy by the name of Maynard Chenowith. He'd been consulting with us on some toxicology problems, and some other things-- he had a background in toxicology. We figured pharmacology would be a might good consulting area on the part of basic research, toxicology, and on the other areas of the interaction of the environment in man or animals. But I'll admit, too, that personally the primary reason was. to act as what I could best call as a 'point of infection', getting us entangled in the area of human health. And I think it's helped to do just that. I don't know that we need to go into the area because it's.recent enough that you know most about it. Chen's done a lot of work in the area of blood prassure, Les McCarty in muscular conduction, and Van Dyke, biochemistry of the area, Walt Piper now is giving us other whole areas in this area but I think it did help in 15685 -28- this area, and of course, one very practical aspect that came out of it is a d a m good anesthetic. And some excellent basic research on why anesthetic works and how they work. Now, we always got most of our chemical substances with which we worked from the Organic Laboratory, Physics Laboratory, you name-- all over the country. All Dow operations. We still do. We still should. Never forget-- you're not an isolated group. You're an integral part of a very, very large research organization. If you don't take advantage of it, too bad. However, by pure chance, and we didn't object at.all, we hooked an organic chemist by the name of Clarence Boyle; I guess he didn't know what he was getting into either. At least, a very small group here who could work close to the biologists from the point of view of structure activity relationship, and point of view of specialized syntheses and things of this sort. Well, you know what Clarence has done-- in many areas. He jumps off the deep end and does many peculiar things. Developed some Interesting organic phosphates that are Important in agriculture now and a cute little material to selectively pick out these sea lamphreys in the Great Lakes. Things of this sort. I think more important, however, are the little things day-by-day he does in connection with the biologist which summates into something. It isn't the individual outstanding thing that jumps out, usually. It's sometimes the contribution to the collective genius of the laboratory. Well, move along. First, basic research is part of all areas of research. Mechanism, actions in toxicology, microbial physiology, bio chemistry of micro-organisms and of the action of chemicals and micro organisms of pharmacology, and so on and so forth. It is not ji field-- it is an integral part of every operation. And we need this as a fundamental basis for all areas. We must not forget that it is the basis of this work; so, while all along some good basic works for some has been done, ^ fO CO 15884 W Z 'L L ? * M o n -2 9 - for heaven's sake, keep it up. And I think the time files and I should end my sermon. Thank you. 1S8S 5 1 5 JO .tr ' O \ Z * ..." ..: Biochemical Research Department THE DOW CHEMICAL COMPANY K ........ .. ; fe:-V--r'?"ft - RESULTS OP TOXICOLOGICAL TESTS ON y j # - 2,4,5-TRICHLOROPHENOXYACETIC a c i d ito- i~ . ::- . . . y. Pile T23.14-23-2 and 3 Chg. 1204 and 5862 Ree'd 3-2-49 and 12-16-49 Pin'd 8-23-50 Work By V.K. Rowe i- .' ^* To Britton's Division |f e >^ ^ , A t t ,n }.J. w . Britton ...y:'' yJ. C. Dosser . Check xcs/j *.> ->-0 Hept- * * - & & & - * < - \ Vi *.-.*- r-A'^O ^w-.'-i^ExAetctu1t-hiDiveepWaR.retWsmee.^anrtScu.hnd.C.eorm,lmaintdt'..e.-e*;&, c;,, .1 ~*.v:i*Agricultural Projects Committee- - . _1-- -- ---- :-- ~o en ^ T O ^ ^ ; ^ Att,ns W. C. Dutton (1) -7r.- Vs^i^VoP-rtl' Ov W. W. Alien 1). .....V.'V.'-'> r t 'c ^ Irish Kaey G.- E:. Lynn 1 1 1 1U DOW CMEMJCAL COMPAHY | 4 f 7`" -UNIT INDEX ^ASfetAy/'^;.. .iTi-r--.`T->-.-:-. .... INDEX HEADINGS ^ s ^ t t ^ A c e t i c acid: ,2,4,5-trichlorophenoxy-. ;.v ..:.....;.,..v.r l)^ ^ P h ^ t3Scitil acid: '2,V,5-tri " -i p r o b l e m . . . . i.5p'V;. 'Al! ^ r*-.!*' '- The widespread handling of 2 ,4,5"trichlorophenoxyacetic acid made it desirable for us to have a significant amount of toxicological information. Data on the oral toxicity was necessary for presentation .2jr& ____________ __ _ v wfcr ;a "to the P.D.A. Hearing on residue tolerances. 15886 } ..... 1 A W v .% v .f -,... i i V 111 r~ 111 i il il 'i \ * ' :J S-- WPWI I. j u f y v r7 T * * * r Biochemical Research Department T23.14-23-2 and 3 Page 2 MATERIAL Names ' ! Formula s I "' 2,4,5-Trichlorophenoxyacetic acid 0 Cl .Structurais H-O-C-C-O-? ' \ci V-- Jtl -7 ./.*. ' -..... -:'' <* CJ1 . . ! O " i - 11''''rs:-^c'.: ( ^ ; ^ ; 7" : B .R .D . K No. 4368-4 -v.L- Sg?m*S V^'V1 ' " ' .o Y>^u-'.-y--- :r-'.--.:Vci-V''.- e -White 267 Bllddgg.'. _ . - References p/.-.Batch 138 (20W-108 SPL 6) .*\ '-r-.-t'v-**--`v'i'gi; ...i.*:.:;\ .feltri V! - ^EXPERIMENTAL RESULTS The acute oral toxicity of 2,4,5-trichlorophenoxyacetic acid eluding ourtestimony on this material we stated, ``Because of the similarity in chemical structure and in `xv&i?:**.*.'?: ...... . i. yr.V *Tl-C''.'*i"1T._*J1'--Ji.~ i f u ^ o x l c l t y :.and p h y s l lo g i a l .. effect _ between 2,4-D ......... . . - . ..-a .- ;. >. and 2 ,4 5~T, it;:Beem:s'J'f&;^c-v^$ u. . ...i-- . . . . . J. . ?. '' "` " .. V^. ^^at^a'Ve'sidue tolerance for the latter on fresh fruits and vegetables'^.; vt.;rshould be .the same as that established for 2,4-D; it would seem that W &%*^*'*'residue of 20 p.p.m. would provide a wide margin of safety."N S\J,V>frc.r Eye'Irritation ' --^-"V'W - V/'i*-1--'-' jtj.-.XLr'.rt--i __ _ a. Tr--- When 2,4,5-trichlorophenoxyacetic acid as a 10# solution in -v-rtf- _rw,4. propylene glycol was introduced into the eye of a rabbit, it produced marked pain and slight conjunctival irritation immediately. Five 1588' hours later, severe conjunctivitis and moderate corneal damage was ^ L '--4 . ` . .. . . - .. -- . 'TP"W Tiinihr; v . w " 11 ; ^apparent*wThis picture remained about.the same'f or ^two ,,days before <*.,*4.4iv a^Sihealing began. Five days after the exposure mild conjunctivitis and {meal damage was still apparent. ^ `" ^Vi. ;r ** -- n.yj Vj' 3' migf--r 'JL$ Biochemical Research Department T23.14-23-2 and 3 Page 3 Skin Irritation When 2,4,5-trichlorophenoxyacetic acid as a 10# solution in ii*. butyl carbitol acetate was applied repeatedly to the rabbit ear and bandaged repeatedly to the shaven abdomen, a slight simple irritation ^ r-K-r- developed in both instances. " - ! ; ' SUMMARY * : - .V . oO 75256 The toxicological properties of 2,4,5-trichlorophenoxy- -I '. '--i -> "I--Ve'iz.,<"**. acetic acid may be summarized as follows: 'K-. ' . 1. The material is moderate in acute oral toxicity for the four 3-v .* ' species, rat, mouse, cavie, and chick. Of these species the rat seems to be the more resistant and the chick the most susceptible. | gf vJv^.^V^ 2. The material is markedly irritating -to the eyesj .^r'Th ''material is slightly to moderately irritating 'to 'ihe'''sMn~v-^:f' -'-upon prolonged exposure. -i 4 - :: . I HAZARDS AND PRECAUTIONS FOR SAPE HANDLING ~ ^ Fsg owin | It does not seem likely that 2,4,5-tridiorophenoxy acetic a***-'.*. acid can be swallowed accidentally in amounts dangerous to life, al! though this might be possible if concentrated solutions of the material / were available : ... to . childf ren. If substantial quantities of the material were to be swallowed by anyone, serious ill effects could be anticipated. If the material should be swallowed, induce vomiting by giving ' a common emmetic V'T*,V*-.7- such as 2 tablespoonfuls ^of table salt v. in . a glass-- .............................. of y* >>;...warm water. iCall a doctor. '? * E1ye ,-*:*** -v. .^ The 2,4,5-trichlorophenoxyacetic acid is capable of causing dierious .damage .to the eyes Precautions should be taken when handling **bt%~UrUl. to prevent poe.ible V ? vV * Biochemical Research Department T23.l4-2>2 and 3 Page 4 X;'.-/: when handling strong solutions of 2,4,5-trichlorophenoxyacetic acid that goggles, face shield, or other similar device be worn to prevent 'i&X 'accidental splashes in the eye. It is believed that the handling of is * * ;'- - .- the solid does not present a hazard simply because of its insolubility f-'-- : in aqueous medium. -.. if t^e matei'ial in any form should get into the eyes, they S2TSMOQ Pi"-should be p-romptly^wa.s.h,ed, .wijth flowing water for at east 15 minutes \5{r: .and medical attention obtained. r t V -f V r-.-'-.v-v t4v - ,.Tf" Prolonged and repeated contact with the skin may result in 1 - irritation. Occasional contacts for short periods are not expected v - t0 cause irritation. Strong solutions are no doubt more likely to cause difficulty than the dry.solid. case.of contact wash the exposed area with soap and water. ..v- - ipS^^vDo^not wear clothing or shoes which have been contaminated with solu** x ` tlons of the material. Chhalatioh ;.^vj studies of toxicity upon inhalation of 2,4,5"trichloro- 'V7.' phenoxyacetic acid dust have been made. We believe, however, that in view of the similarity with this material to that of 2,4-dichloro- phenoxyacetic acid, that it is unlikely that toxic concentrations of **.~r the dust would be inhaled, primarily because of the irritation it will produce upon the upper respiratory passages. 15889 . , -- --- .. 0 ,..- -*-T ,:<i ~i r --IirftiW fcw Ui *.. A* ~ *- ' >N . O THE CHLORACNE PROBLEM - BIOCHEM'S CONTRIBUTION 1 5 3 ft Date f / n j s r Pile D O W 747532, SUMMARY An outbreak of chloracne,, in the trich lo ro p h e n o l process in 199 B u ild in g and in 349 B u ild in g has re su lte d in approxim ately 40 cases of chloracne in Dow people. R ie outbreak was p re c ip ita te d p rim a rily by a s e r ie s of process changes which increased the pro duction of a chloracne-producing impurity in trichlorop henol. Increased exposure to operating and to maintenance .personnel a ls o contributed. Much e f f o r t by persons in the A n a ly tic a l Laboratory, the Toxicology Laboratory, and the Environmental Research Laboratory has re su lte d in the is o la t io n and id e n t if ic a t io n o f one 1 '.-.''AI eI -' "im p u rity which i s capable of having caused the d if f ic u lt y ,a n d has U* isr- a lso resu lte d in co n tro l of the exposure s itu a tio n so that no new cases of chloracne have appeared in the la s t fo ur months. Some k \ other compounds than the one alread y is o la te d and id e n t if ie d and f- studied are capable of producing chloracne. T heir sig n ifica n ce in the trich lo ro p h e n o l process i s not yet known. CHLORACNE .!I Chloracne is a skin disorder characterized by the appearance of black-heads and small bumps. These appear first'on the face of the individual affected, Depending upon extent of exposure, the skin I i disorder may spread to other parts of the body. Infection and irritation of the skin rash may cause enough discomfort of toher 15890 2 individual to result In time lost from work. This happened in two of th trlchlorophenol,cases . The materials known to cause chloracne In humans are usually chlorinated complex organic molecules. The compound Isolated from O trlchlorophenol caustic insoluble oil is 2,3,7,8-tetrachloro-^pp</ilo^^o O bc&eodloxln (symmetrical ). m m " (r fi* et 747533 V-iJ -&.: .=m-s6v'- This compound and others which have been shown to cause 'chloracne have also been shown by animal tests and some human ^experience in other companies to produce liver damage if the exposure |l8 more extensive. Thus far, no liver injury has been detected by clinical examination of the affected Dow people. Two aspects of the ailment are distinctive and somewhat frustrating. First, there is a latent period of approximately two months after sufficient exposure before the disorder is evident on the person. Secondly, once a person has contracted chloracne, the recovery period is from about six months to two years for the cases which Dow has encountered. In some Instances, the Europeans have encountered recovery periods as long as five years before .the man was completely free of J^-'chloracne. 15891" __ 3- n s u L MO TOXICOLOGY RESEARCH In 1941, Adams, Irish, Spencer and Rowe of the Biochemical Research Laboratory published a paper in Industrial Medicine on ^The Response of Rabbit Skin to Compounds Reported to Have Caused Acneform -'i> 4 Dermatitis". They described the animal test using the rabbit ear, ; -* which has been extremely valuable in the studies of compounds which may cause chloracne in humans, lherabbit appears to be very sensitive to such compounds, but it is non-specific, that is, the folliculitis IM#5 which occurs in rabbits does not identify the particular agent. Another .'i'JV- shortcoming of the rabbit test is the period of time necessary for the folliculitis to develop. There appears to be an induction period of approximately one week for theddioxinJ hereafter abbreviated TC|D,) ' to produce folliculitis in rabbits regardless of the severity,of j r aeflef*** j exposure. There is 9m m evidence that unknown^ may produce folliculitisi ft fin rabbits with a shorter induction period. Before a particular test % .i sample is exonerated, the test is run for four weeks of repeated daily application to the rabbit's ear. In 1944, research in the Benzene Research Laboratory produced a severe case of chloracne and toxicology studies on animals showed that the probable culprit was a chlorinated double ether produced from the experimental solvent being studied. At this time, samples from the trlchlorophenol process were also studied and the caustic Insoluble oil was shown to be active by the rabbit ear test. There was no human experience with chloracne in the trlchlorophenol production group at that time. The/product was shown to be inactive by animal testp.- 15892  O W 747535 -4 - In 1955, a number of German manufacturera of trichlorophenol and at least one French company had human experience with chloracne that caused them to shut down production plants and to study the problem. Their studies contributed mefe to the medical picture and t to process Improvements, but not much to the toxicology o f t he situatloi The Germans 4ML Isolatedthe TCD and o some limited animal studies on It and on some chlorinated dlbenzofurans (dlphenylene oxides) but this a T <s was/very limited amount of work. They-did even leso 1 teltg evaluation th exposure* of their people which led to the Injuries. In 1957/ a series of process samples were acquired from 199 and 349 Buildings and tested on animals. The tests Indicated that the caustic Insoluble oil and coll reactor product in 199 Building were active and that the tar from the color stills In 349 Building was *w also active. The precautions first recommended in 1945 were re-emphasized. There was still no human injury.in the trichlorophenol process. About 1956^ impurities in trichlorophenol produced by Dow and Hooker were Isolated and studio^ by animal test and shown to be inactive ill (TBTms i<* r M Over the years, some samples of end products such as Silvex, j Q^onnel, and 2,4,5-T acid have been tested on animals and in no case, was chloracne activity detected in these products. ,J process b ' In 1962, supervision of 199 Building sent/samples//from the I | \ then existing process and from a pilot run J L pji&poaaffi change in the -pr^pflg whlnh wa? a decrease in the caustic concentration, in-the- j a^arttng_maer 4*ls. These samples were tested on animals and again i 15893 ! W747536 the caustic insoluble oil was shown to be active but no more active in the new process than in the old. The Biochem report reiterated the precautions necessary in handling the oil and the change was made at 199 Building. There was still no human injury. When the chloracne outbreak occurred in early 1964* many more process samples were tested on animals with particular attention to the caustic insoluble oil. Two samples of this oil were dramatically differentf.qualitatively than those tested before or since. These two samples killed the rabbits when applied at the same concentration as has normally been used. The oils had to be diluted to concentratio before the animals survived and showed folliculitis. Hie normal test concentration of caustic insoluble oils up to that time had been 10$ dilution. Subsequent studies on the TCBD have indicated that the amount of TCBD in these two samples of oil isfnot sufficient to cause i j I j j j |the death of the animals. In July of 1964, the rabbit ear test was f; fused for the first time on wipe samples of the building equipment and surfaces at 199 Building. The wipe tests indicated extensive contamination of 199 Building. This test has been repeated periodically; to the extent that over 600 animal testa have been run since I w t July/^, directly related to the chloracne problem. A representative oil sample was selected in August 1964 to j be fractionated in order to isolate and identify the chloracne-producing; impurities .'^Skelly of the Analytical lab isolated a number of fractions which were identified, among them the TCBD, which was also synthesized ! jby Skelly fromlfrbenzodioxin. The two materials were identical 4informs -ef lnfraredy&nd^nelting point^, and both showed extreme activity on the 15894 " 6- - rabbits. Other fractions indicated little or no activity pn the animals ( v/ C ) The isolated material was utilized by VPC*to standardize/a/method fop detecting this impurity. Harold Gill's group in the Analytical Laboratory has consistently improved the VPC sensitivity in process samples so that at the present about 1 pprn^or TCBD may'be detected In various process samples. However, the animal studies have indicated C opies bt'/hhi that rabbits are sensitive to TCBD down to approximately 5 ppb^upon v repeated application to the ear. The rabbit test remains the most D O W 747537 sensitive method of detecting acnegenic activity. iftawsMS^, ingle application studies on TCBD indicate that parts per million are necessary for a response so that VPC does provide a first step in ZIP evaluating the hazard from TCBD specifically.^ tyAny wipe samples and process sample# lhave indicated by VPC,/Gntfnowns in JShe regrlbn of thlch we/sufepect afre/also acnes#nlc J Sample?' 4t ch!6rlnated wipe samples with no detectable TCBD but flubSYaritlal amounts of unknowns i have shownfactivity on the animals thajfl can ( be accounted for by the 7t*6Q low level of dioxin-which may be present. The chlori ted di.benzofurans 15895 ih .--. ' r ~yt ;' r 6? A //C f rft* nr-: DOWS 7 4 7 5 3 9 7- purified and tested sain on animals, The posBlbili^r] exists that thi fV are ^4nt.^iinat/ themselvjes Tdj ls posiribilitynas Tiot reen invfl/stbgat'ftd/as yet. More detail on the results of process sample and wipe sample . testing on animals will appear in the sections under specific building numbers. , / J , ^TruUo..^., Studies are noW in progress on Dow and products^and those of other manufacturers for acnegenic activity. Thus far, no Dow end products have shown activity on animals while some other manufacturer^ end products are showing activity on animals as well as detectable dioxin by VPC analysis. The Analytical Laboratory and the Toxicology Laboratory are presently conducting a project to determine the -'/'*%*V*`,-'.., analytical and animal test limits of sensitivity for TCBD in various Z- Dow products -ataetejmg from trichlorophenol. This project is aimed at r ^developing a quality control specification for -the dioxin in consumer v ^products. 199 BUILDINfl The first animal test, on trichlorophenol process material: was conducted in 19^5 > at which time the caustic insoluble mil was shown to be active. Precautions were recommended at that time. The second animal teBt took place in 1957. The caustic insoluble oil was again active and the coil reactor product was also active. Other process samples were not active. Precautions were>*,recommended again for handling the oil. 158-97 o p sa u m o q -8- In 1955 > the C. H. Bc/jringej^Totan ^ 0 Company in Germany asked for information from the Qivaudan Corporation, which company referred the request to Dow. A letter describing the hazards and precautions for safe handling of 2,4,5-trichlorophenol was sent to Bcfringer with a data sheet from Blochem enclosed. The letter answered seven specific questions regarding our own plant experience. In 1957, Bctringer sent Dow-and all other known trichlorophenol manufacturers a letter describing the ttfce of. their research on chloracne in the trichlorophenol process. The letter described the danger points in the process and the limits which had to be observed in order to avoid producing acne exciter in trichlorophenol and tn 2,4,5-T acid. A temperature limit of 150 C for the MaetetUta was emphasized by Bctt*inger. .1 ? In 1962, the above mentioned animal test indicated that the *ft* !caustic insoluble oil from a 73# caustic process and from a 24# caustic i process were the same in that they both produced folliculitis on animals m r about the same ew t f of response. The Biochem report reiterated the precautions but stated there was no evidence of increased hazard in j the new process. II j In July 1963, 199 Building started up on new tetrachlor<benzen< / J*'* V-*' 1 ^ Whlch^caused line plugging problems and increased exposure of personnel 'according to thefauperintendent. In November and December of 1963, the 1 1 plant ran at capacity. The caustic insoluble oil production was above JV , i normal and the oil was drawn off more frequently,^It was also being Jj -sampled regularly. The samples were taken to the^lao for freezing point: analysis. The temperature at which the plant process was run was also - 9- i n c r e a s e d ") xi. * n January 1964, the first medical report of frtae case of / chloracne initiated survey by the Environmental Research Laboratory. trichlorophenol OtW a n u ary Q3 j lQ^^S, "^he/operatorte Job was studied closely and a report issued on 2/5/64 recommending changes in the procedure and in personal hygiene habits. Some changes in the oil draw-off equipment and procedure were already initiated before the Environmental Research survey got under way. In the spring of 1964, process equipment changes T i* * - were made by the Phoenix Sprinkler Company and at this pm tut, the caustic Insoluble oil samples which killed the animals were taken at the plant. In July 1964, the first wipe samples were taken. The building was found to be extensively contaminated. Some air sampling was begun at this qp time. No activity was found in the air samples. In August 1964, VPC ,^ -re & & & ~ rc*$ r'KMietected tetrauhlorobenzodtoxlny. yhe oil was fractionated, tUa dfceiiin*** 7P isolated and identified, and was also synthesized. In tUmmetaekl of 1964y mere eaoeo ef chloracne appeared, Phoenix Sprinkler men, some area shop people, and more 199 Building employees developed chloracne. Wipe samples indicated continued contamination. Extensive clean-up measures were undertaken. Wipe samples showed improvement but not complete elimination of the contamination. "implnn rtr a^ilve . 1 In late October 1964, there was a flare-up of some existing chloracne cases in 199 Building people. This was brought on by exposure to hot fumes from a screen in the phenate product line. Animal tests showed that this phenate was active and that the screen residue was extremely active. This phenate went to 349 Building and is the probable cause of the 15898 10 three cases which eventually appeared in 349 Buildingf About November 1 1964, very stringent safety precautions were instituted in 199 Buildin These Included a full-time health supervisor i m M y whose Job was to review each and every maintenance or installation Jobyin th> raaatey m b s -to specify the detailed safety procedures which the men should follow. Clean-up activity continued and extensive modifications of equipment and the building of an enclosure around parts of the process 0A<took place in November and December of 1964. irttmomUy hundredA-^f outside personnel were involved. Wipe tests indicated improvementsin the contamination situation and air samples ajfcri. showed no activity on the animals. In 1965* the full-time health supervision continues. VPC analysis is now being used for quality control of the phenate leaving the building. Wipe tests show substantial improvement. However, ^ \ air samples are beginning to show activity on the animals, although * only one air sample thus far has shown detectable dioxin by SPC Tp analysis. A very significant factor is that to the present date, there have been no new cases of chloracne since the institution of the full-ti health supervision and extreme safety precautions. Two cases have appeared at Medical since that date, but both of these have shown that the individuals were in the area and had possible exposure prior to the November 1st date. Since the induction period in people is about two months, and it is now approximately ubftee months since the height#'of activity in 199^with the many outside personnel, there is evidence that the safety precautions which were used were satisfactory. These precautions are being continued on Jobs in 199 Building. 15900 - 11 0 349 BUILDING v o w 747543 Sodium trichlorophenate from 199 Building is received -fcy^ . l-iUy 349 Building where it is neutralized^ which effcgfeff a ten-fold con centration of the material to provide crude trichlorophenol. This o trfy u iL "wet feed" is t through a drying column; the "dry oil" is then distilled in two color stills. . The first animal tests run-or^ 349/samples in 1957 indicated activity only in the tar from the color stills.. This was mild activity, less than that demonstrated by the caustic insoluble oil at 199 Building Similar samples taken in early 1964 again showed the tar from the color stills to be active. Samples taken in October 1964 showed activity in the wet feed,,,the dry oil and again,,the tar from the color stills. The , product was still not active.on animallsb ./ Samples taken in November 1964 tshowed activity again in the wet feedr^*^hhe d-ry oil and the pr-o-d-u-ct - inactive. The degree of activity in the crude material^ was less than that in the October samples. , The contaminated phenate a ned above-; at the end of y October 1964^was processed by 349 Building. The activities : pipe fitters and an operator at 349 /? early Novetnbeiv>lnvolved c l e a n i ^ | . . ----- ^ I lines and changlag- valves in lines which had carried the contaminated phenate. The actual exposure that brought on chloracne in the 349. j Building personnel ,ifl not definitely established but this is the most likely situation which could have caused it. In early November, Clare Bailey, 349 Building Superintendent, Issued a written sheet describing precautions to be taken because of the 1590^ - 12 - D O W 747544 -J*2f potential hazard. This resulted from the 199 experience and was s promulgated on Bailey's initiative as a precautionary measure. About the first of this year, 1965, objections by workmen to working in 349 caused the adoption of full-scale protective measures in that building in regard to the trichlorophenol process. Further complaints caused the extension of such precautions to the entire reactor room, including the bisphenol process. Wipe tests eventually indicated that the O/Wti'Yt' -- bisphenol^ie- free of contamination. In fact, only limited areas of the trichlorophenol section show contamination. Clean-up and further wipe tests are being delayed until process equipment has been moved to a new location outid the work area of 349 Building. Extensive clean-uj will be necessary in the alleyway behind 3^9 because of contamination from the trichlorophenol tar. ! A health supervisor is now stationed at 349 Building and full ! ^precautions, are being taken on any Jobs where exposure is possible. Onlj j. <3 cbbflJUSYVL-' yjf three c^aes^have shown up at 349 thus far, none since the incident in early November. Composite samples of finished trichlorophenol from 349 have been run on animals at either a 10 or 1% concentration in Dowanol.HM. Under these conditions, no finished product from 349 has shown activity /fir / on animals. Quite recently, VPC has succeeded in lowering sensitivity ; f for TCBD in trichlorophenol to about 1 ppm. They have since analyzed some retainer samples and found some with detectable p f :- C plus unknowns that appear in the same place as the chlorinated benzofurai j These samples were extracted with chloroform for analysis. The chlorofo:1 extracts, wherf'placed on rabbits'ears, are showing activity. 15902 \ - 13 - O V / 747545 Another t a r , the c a t c h - a ll t a r In 3^9> has shown some s lig h t a c t iv it y on anim als. This i s the resid ue from c a t c h - a ll d i s t i l l a t i o n fo r 265 B u ild in g . The " c a tc h -a ll" m ate rial i t s e l f did not show a c t iv it y The t a r from the d ic h lo r s t i l l was not a c t iv e . T a r, ctrude product and f in a l product from the Dowicide 3 process are c u rre n tly being studied on an im a ls. f Dowicide 3 In the p a st'n a s been regarded as a p o te n tia l chloracne-producing m aterial. 267 BUILDING Fin ish e d trich lo ro p h e n o l from 3^9 i s processed in 267 B u ild in g to 2 ,4 ,5 -T acid and to 2 ,4 ,5 -T e s t e r s . Process samples taken in e a r ly 1965 showed no a c t i v i t y wi.th one; exception. The resid ue from the sodium s a lt f i l t e r p ress showed s lig h t , I a ctiv ity 'o n the rabbit ear. j to T4 I j {\ Wipe^baabe in 267 B u ild in g are s t i l l in progress but show no j * :activity at this date. i Human experience in 267^would- ind icates no problem in the p a s t, A- f but the cir c u mst ancoD of exposure/lead t o grave oonoorn ever fu tu re pro b lems i f contaminated m a te ria ls are processed at 267 B u ild in g . 265 BUILDING i A number of Dowicides are produced and packaged in 265 Building, Pentachlorophenol, tetrach lo ro p h en o l, and others are among the p rod ucts.' Di Penta- and t e t r a - have long^b^en ^cnOMn to be capable of causing chloracn Jltae/uman experience at 265/itx^s in d ica te d no p a r t ic u la r problem; only an o ccasio n al case^ through the years haB been reported at M edical. At the j *I present tim e, two in d iv id u a ls , an operator and pipe f i t t e r have beenj -- OW. 747545 reported to have mild cases of chloracne. Process samples are currently being studied on ttre animals. No wipe testing has been done as yet at 265 Building^ttaelT'. 266 BUILDING Three cases of chloracne have been reported from 266 Building. None of the processes or materials in 266 Building have been known to cause chloracne ip the past. Its proximity to the Dowicide plant Kae- -been invoat'iQnIad lij> y1iInn_jjr rljii1 tests in 266 Building p JFtoc ess samples ^erfthe parahydroxybenzaldehyde process have also been tested on animals since the most significant case is in an operator on this proces None of the process samples were active; only one wipe test(on the mobil elevator in the warehouse sectionjwas active on animals, nils elevator has been decontaminated and painted. It is difficult to explain the contact which resulted in these three cases of chloracne. \ i i 2-0--6--B-U-I-L-D-I-N-G- i! ! This building has three cases of chloracne in operators who hav ^ ^j worked on the finishing and packaging end of the 6X process. 6X has bee: i known as a chloracne-producing material for many years. The cases in thj building were reported to Medical in the middle of 1964. Study of the ! I finishing end, distillation and drumming-off of 6x, indicated numerous j I opportunities for exposure. The process was not running on 6x itself, bu on &fnocuous material using the same equipment and the circumstances as j a. '6y~#irlfiewbclon .-- Wipe tests were made of the equipment and area but no . 6X was detected in any place. In prndimnrl ,1jfi the north end Bu4JttLEUg'& the. process equipment has been idleW j..riipe tests on -&& indicate / `l ^ J.'i3C4 D O W 747547 - 15 - 6X contamination. This equipment is presently being cleaned up for other serviceprecautions are being taken. The Dowicide 3 process will soon be moved, in its entirety, to 206 Building. Plans have been made to study it thoroughly in its initial operation in 206 Building. 206 Building is a neighbor of 199 Building and for this reason the question of neighborhood contamination from 199 was investigated by means OC wipe tests in spots likely to have been contaminated by 199 effluents. None of these wipe tests were active. Some wipe tests at 199 itself indicated a rather quick drop-off of activity with distance from the vent on the roof of 199 which was the source of roof contamination \\J /\\ at that building. c* X yV - 1603 BUILDING Bradley's group in Cheo^3Thysics Research Laboratory has been ru Btudying variations offtrichlorophenol process. Two of the group contracted severe cases of chloracne about two and one-half years ago as the result of exposure during laboratory runs. Their former work area in 294 Building and their present work area in 1603 Building were wipe tested and no active samples were found in either place. I j I ! Laboratory samples have been submitted by this group occasional! in the last two years, appra.1 mate-tyr" Many of these samples have demon strated activity on the animals. 474 BUILDING ^7 Widlger's group in^Benzene Research Lab has been studying the - current trichlorophenol process. Wipe samples have been taken of the work areas in 474 Building. Those that have been completed showed no .i***t*> 159G5 DOW 7 4 7 5 4 8 V -In activity . 703 BUILDING The Waste Disposal Department handles the caustic Insoluble oil from 199 Building and the tar from 3^9 Building, both of which are active. Wipe samples have been taken in the tar burner area. Soil samples were also tested and wipe samples of the vertical tar burner are In process. Some activity was found on an area around the tar burner. Waste Disposal has been advised of necessary precautions. Other possibly contaminated effluents have been discussed with the Waste Water group of Waste Disposal and arrangements made for necessary precautions when called for by work on waste disposal lines. V Larry Silversteln 'March 10, 1965 1 .if DOW7.46.900 MN 0 69799 MIDLAND, MICHICAN July 25. 19^7 W. J . McCoy Bioproducts Sale* : ' BPC ' c c : W. L . Corbin, BPC *.* * k V-'-' -..V .-'<!/U,..'. : ' 'j''**` .-.rj: .. ' 2, 4 ,5 -T FORMULATIONS I appreciate v ery much youv note of 7 /1 7 /6 7 in which you informed me that som e Diamond m aterial ha* apparently caused serious skin prob> lerns among people applying the m a te ria l. This goes along with a -- rep ort that recently appeared in the South A m erican literatu re which states that m aterials of this nature have also been noted to have caused sim ilar difficulties.-.J am enclosing a copy of this publication ? Z .:? r~. *o. r . Tur inform ation." r -** *" . if would appear that our predictions of a few y ears ago a re beginning ' /Jr . to come to pass, unfortunately. F ran k ly , 1 am mighty glad that we v **< * >3;* took the position *re did. i'-* .. s E i y P le M e continue to keep me informed as best you can. '.'..tvj. t t rt`|Vr .*" .*,,/- . *rV - . t . ' __V. K . Rowe . Biochemical Research Laboratory 1803 Building crSi V v"> ': - ' ... pgw teiA 3>v bcci-AT. K . Rowe (2) Correspondence *c.' - I. S l L a i 15934 A" .r' 'i*',V n'.. ' J* --. J- - * ' j . - V /* yn.*v -JL5o 3 -i- PL 2172-1 THE DOW CHEMICAL COMPANY IIDLAND DIVISION April 25, 1967 X. E. Coulter Midland Division Research & Development 566 Building CKLORACNE RESEARCH PROGRAM History of Chloracne Incidences at Dowt Historically, Dow Chemical has been involved in chloracne incidences ever since Dow began the production of chlorophonols. At first, the commercial production of chlorophenols was conducted at 206 Building, During the period 1934-36 there was a severe outbreak- among the employees which resulted in an unsuccessful lawsuit. The chloracne incidents were traced back' to poor working conditions and the manufacture of Dowicide P. The manufacture of Dowicide P has since been terminated. New and improved working facilities for the Dowicide group were constructed at. 265 Building in 1940. In the-late 1930's, Wes Stoesser in 2QA lab got a serious chloracne attack from chlorinated diphenylene oxide. Drastic treatments were used to cure this incident and no further work was cone on this series of compounds. It is suspected that many of the other incidences of chloracne are caused by chlorinated diphenylene oxides or analogues thereof. In the next ten years, another imfortunate situation occurred in the chloracne situation. Some of the Dow customers complained about dermatitis and/or chloracne from the use of__Dow's ' Dowicide 3* I understand financial adjustments were made and" th production of Dowicide 3 terminated. A purified material of related structure is now sold as Dowicide 31 and 32. During the period 1940-65* the product 6 x (diphenyl oxide chlorinated to the hexa level) was manufactured at 206 Building and at least one severe case of chloracne occurred because of this product. The production of 6X has been, terminated. In the research lab at 172 Building, there were some cases of chloracne from research exposures. In one case, a severe case resulted from the recycling of residues from the manufacture of 2,4,5-trichlorophenol using glycol as a-solvent. In another case, several mild cases occurred hydrolyzing polychlorobenzenes using aqueous caustic at high temperature. The Chemical Physics Lab had several incidences of chloracne from the recycling of caustic insolubles in the alcoholic caustic hydrolysis of tetrachlorobenzene. lS'S'S , -il- -2- PL 2172-1 In 1963 the 2,4,5-trichlorophenol hydrolysis step at 199 Building was modified for economy and safety reasons from the use of 100$ caustic to 23$ caustic. The rabbit test for chloracnigens in the caustic insolubles obtained from a pilot run at this time indicated that the test response for chloracnigens showed no difference between caustic insolubles obtained by either procedure. During the latter part of 1963 the production department, in order to increase capacity, raised the reaction temperature and increased the throughput. This meant that more caustic insolubles were produced, and more Dempster loadings had to be made. This meant that employees had more exposures to the caustic insolubles, and the caustic insolubles due to the higher temperature had larger concentrations of chloracnigens. Thus the higher concentration of chloracnigens and the more frequent exposure caused many mild incidences of chloracne in 199 Building and two severe cases (LTI's). In 1966, a- new process (Boehringer) was put into operation using a batch reactor at low temperature, and so far has operated satis factorily. _ After they started up their Dowicide plant, the Canadians began to experience chloracne incidences in their employees. In Midland,, more than half of the Dowicide employees have chloracne of varying intensity and it is impossible to say when or where these incidences occurred. R esearch Program in P ro g re ss fo r C h lo ra c n e R e d u c tio n : Because of the prevailing existence of chloracne in the Dowicide plants and a sincere desire to reduce or eliminate this, research has been initiated in 1966 on this problem. Progress has been slow due to the complexity of the problem. The problem involves isolation and determination of the identity of the chloracnigens. After being properly identified, work can progress on its reduction or elimination in the process. In commenting on chloracne, we must keep in mind that chloracne is a cosmetic evidence of the attack and serious liver damage, is an invisible effect of the attack. Rabbit ear tests are a positive sensitive method of d e t e r m i n i n g the chloracne activity of chlorophenol impurities. P re s e n t K n ow ledge o f C h lo ra c n ig e n s ; Compound A c tiv ity 2,3>7, 8 Tetrachloro - Very positive C I 1 - 3 - Not active C1s - t - Possibly some cpds. acldflfe Cle - Not active V e ry a c tiv e . 15336 Compound - 111-3- PL 2172-1 Activity Very active . - Unknown activity Cl1 -2 - Unknown activity Cla-e - Some very active C I3 + - Some activity Materials possessing unexplained chloracne activity: Some Midland batches are mildly r--reactive - . Many Canadian batches are mildly reactive ~ . l... _ OE C Cl C Cl Cl Dowicide G All. sludges are active 15937 D0WJ514318 . Compound iv : PL 2 1 7 2 - 1 Activity - active Midland Research Program on Chloracne; The following chloracne activity fractions are being examined for isolation, identification, and minimization of chloracne activity. Unfortunately, due to shortage of technical help, the program is proceeding quite slowly. 1* Dichlorophenol still residue. 2. Pentachlorophenol process samples. a* Dowicide 6 and 7 "active" batches. b. Dowicide G sludge. c. Dowicide G scrubber sludge. The method of research is to'first concentrate the sample (remove chlorophenols); then fractionate by chromatography; test fraction on rabbits, then further fractionate by chromatography, then test fraction on rabbits; etc*,. rthen determine structure by micro analysis; then determine method of analysis in original sample* and then investigate process changes which will minimize the chloracnigens in the process. The Benzene Research Lab and the Biochem Research Lab are collabora ting in this project. The Benzene Research Lab dees the chemical research and the Biochem Research Lab does the testing on the rabbits on their charge. i.'v' Alex 'W'idiger Benzene Research Laboratory 474- Building Je cc: W. H. Haberstroh.' 474 Bldg. R* C. Sauers, 474 Bldg. S.. L. Bender, 172 Bldg. E* C. Staehling, 258 Bldg. L* Silverstein, 1701 Bldg. 15938 DOW 1514319 ooezeziMoo# Tr C VJ .1 b J M 1C A L C O M P A M Y MIDLAMD, Michigan June 1969 ___ as :Z O A;" A. A s a d c r i a n Halogens R e s e a rc h ' Labo r a t c r y 7co Building O XI ** 0 c c : E . H. So lem, Halogens R e s e a r c h L a b o r a t o r y , 7 6 8 B u i l d i n g J. P. M i l l s , C h e m ic a ls L a b o r a t o r y , 3 3 5 B u i l d i n g P. C. L e a v i t t , Halogens R e s . L a b o r a t o r y , 7 6 8 B u i l d i n g A. E. S c h o b e r , T o x i c o l o g y L a b o r a t o r y , 1 8 0 3 B u i l d i n g V. K. Howe, T o x i c o l o g y L a b o r a t o r y , 1 8 0 3 B u i l d i n g ?. L Dunn, T o x i c o l o g y L a b o r a t o r y , l 3 0 3 B u i l d i n g 2 , 3 , 7 , 3 - T e t r a b r o m o d i b e n z c - p - c i o x i n app ears to be a s p o ten t an acr.egen a s i t s c h l o r i n e a n a l o g , which i s known t o be th e main o ffe n d in g m a t e r i a l in the t r i c h l o r o p h e n o l p rocess chloracne problem o f a few y ears ag o . A sample o f h exa b ro mo aip h en yl o x i d e was t e s t e d i n 1 9 6 5 ana a sample o f a e c a br om od ip he n yl o x i d e was t e s t e d r e c e n t l y . N e i t h e r showed a r e s p o n s e on th e r a b b i t e a r t e s t f o r c h l o r a c n e . Dow 6X ( h e x a c h l o r o d i p h e n y l o x i d e ) has c a u s e d c h l o r a c n e i n humans and a r e s p o n s e on a n i m a l s ; c c t a c h l o r o d i b e n z o d i o x i n was in a ctiv e on the r a b b i ts . Because chloracne is a d is tre s s in g illn e s s which requires a long time t o c l e a r up i n humans, and b e c a u s e th e t e s t d a t a on b r c n i n a t e d compounds i s so l i m i t e d , I would recom mend t h a t v e r y good p e r s o n a l h y g i e n e and ho u s ek eep in g h a b i t s be follow ed i n working w ith brom inated diphenyl o x i d e s , until furth er assurance of a lack of hazard is forthcoming from toxicology t e s t s . _ I recommend f u r t h e r t h a t i f b ro m in ate d d i p h e n y l o x i d e s a p p e a r t o be an im p c r ta n t item in Dow's f u t u r e , mo re samples be submitted to the Toxi logy L a b o r a to r y f o r t e s t and in p a rticu la r, any process noies from p ilo t plant or productio; o p e r a t i o n s , i n c l u d i n g wa e s t r e a m s and i n t e r m e d i a t e p o i n t s v.'here human e x p o s u re may c c u r . I n l a b o r a t o r y t e s t s by A l e x '..`i d i g e r , c h l o r i n a t e d ph I s and t h e i r sodium s a l t s s u b j e c t e d t o t e m p e r a t u r e s > 1 5 CC p o a e e c a c n e g e n s . S t i l l bot to ms and d r i e r r e s i d u e s from : w i e l d es p r o d u c t i o n a l s o show acnegenic a c t i v i t y in an 3. -- 0 6 Z 3 15939 -/ l 0 R 7 7 1 MO n A. A- Asadorian o June 4 , 19 6 9 Ci i pre: his latter is an inadequate explanation For mere beta ileo information on our no ledge of eh Iona co e olease contact me. '1. G. Silverstein Biochemical Research Laboratory 1 7 0 1 Building/5--4676 National Agricultural C hemicals Association AiSOClATlON* IUI101HG 114 S NINETESNTH STSEET, N. W. WASHINGTON 4 # 0. C. 1609 TIKPHONIi STIIIINO 3-3133 JANUARY 2 2 , 1960 MR. MARVIN 8UGH HEAD LANDSCAPE ARCHITECT LANDSCAPE DEPARTMENT INDIANA STATE HIGHWAY OEPT. STATE HOUSE annex INDIANAPOLIS, I NOI ANA DEAR MR. BUGHt I T HAS COME TO OUR ATTENTION THAT THE INDIANA STATE HIGHWAY DEPART MENT IS CONCERNED ABOUT RECENT STATEMENTS ISSU ED BY DOCTORS AT THE MAYO C L IN IC IN WHICH THEY REPORT ALLEGED E F F E C T S ON HUMANS WHO HAVE COME 141 CONTACT WITH 2 ,4 - Q OR SIM ILAR PRODUCTS. IN RECENT YEARS 2 ,4 - 0 HAS BEEN ACCUSED OF BEING RESPO N SIBLE: FOR MANY IL L N E S S E S AND EVEN HAS SEEN 8LAMED IN CAUSING DEATHS IN HUMANS. IN 1957 A WOMAN BLAMED EXPOSUHE TO 2 , 4 - 0 SFRAY AS THE CAUSE FOR HER DEVELOPING ASTHMA. AT THAT TIM E WE CONTACTED THE U . S .. P U B L IC HEALTH S E R V IC E TO DETERMINE WHETHER ANY DOCUMENTED INSYANCES OF 2 , 4 - 0 POISONING HAO BEEN REPO RTED . I WOULD L IK E TO QUOTE EXCERPTS FROM A R EP LY TO OUR INQUIRY SIGNED BY O R . VAYLANO J . H A YES, J R . , MEDICAL Director, chief-, toxicology section, communicable.Oisease center, U. s. Public health service. WE HAVE NO RECOROS OF INJURY TO MAN CAUSED BY 2 , 4 - 0 OR 2 , 4 , 5 - T WHEN USEDW ITH O UT S U IC ID A L IN TEN T. MORE RECEN TLY WE HAVE HAO AN INQUIRY FROM A P R IV A T E PH YSICIAN REGARDING A WOMAN ABOUT 5 0 YEARS OF A G E, WEIGHING 185- POUNDS, WHO CLAIMED THAT SHE WAS EX POSED TO A CLOUD OF 2 , 4 - 0 SPRAY. W ITHIN 10 MINUTES AFTER THE EXPOSURE SHE SUFFERED FROM A PARCHED THROAT AND 15 MINUTES LATER HAO D IF F IC U L T Y IN BREATH ING SIM ILA R TO ASTHMA ANO TH IS CONDITION HAS P E R S IS T E D U N TIL OCTOBER 3 1 , 1 9 5 7 . THE EXPOSURE WAS SUPPOSED TO HAVE OCCURRED OURlNG THE FA LL OF 1 9 5 6 . THE WOMAN'S HOME WAS ABOUT 1 5 0 F T . FROM THE ROAD WHERE THE SPRAYING WAS DONE. SHE WAS IN THE KITChEN AT THE T IM E . SHE CO cr: cr cc ro c _________________________1 5 9 4 1 DOW1 3G6921 . MR. MARVIN BUGH Pa g e two HAD BEEN TOLD BY HER PERSONAL PHYSICCAN" THAT SHE HAO AN ENLARGED HEART. IT MAY OR MAY NOT BE THAT THIS CASE IS THE SAME AS THE ONE WHICH YOU REFERRED TO. IF IT IS THE SAME, THE CHANCE THAT THE ILLNESS IS RELATED TO THE EXPOSURE TO HERBICIDES IS REMOTE TO THE POINT OF BEING IMPOSSIBLE. AS WE MENTIONED IN OUR LETTER TO THE INSURANCE COMPANY, IT IS NOT POSSIBLE TO EXCLUDE THE PO SSIBILITY THAT ONE OR BOTH HERBICIDES MIGHT CAUSE ALLERGY: I'NAA FEW HIGHLY SUSCEPTIBLE INDIVIDUALS. HOWEVER, THE CHANCE THAT ONE OF THESE MATERIALS, OR, IN FACT, ANY MATERIAL, WILL PROOUCE A CONDITION OF CHRONIC ASTHMA WITHOUT FURTHER EXPOSURE IS ABSURD. IT WOULD APPEAR MUCH MORE LIKELY THAT THE WOMAN IS SUFFERING FROM A CONDITION OF CARDIAC ASTHMA ANO THAT HER CONDITION IS NOT RELATED`TO ALLERGENS OF ANY SORT. I WOULD ALSO LIK E TO QUOTE FROM A LETTER FROM OR. HAYES IN REFERENCE TO PUBLISHED PAPERS ON THE TOXICITY OF 2 ,4 - 0 ANO/OR 2 , 4 , 5 - T . THREE PAPERS ON THE TOXICITY OF 2 ,4 - 0 ANO/OR 2 , 4 , 5 - T ARE AS FOLLOWS: D R I L L , V . A . , ANO H IRATZKA, T . : T o x i c i t y of 2 , 4 - o ic h l o r o p h e n o x y a c e t ic a c id and 2 ,4 ,5 - tr ich lo r o p h en o x y a c etic a c id * A r epo r t on t h e i r a c u t e and c h r o n ic t o x i c i t y in d o gs. A .M .A . ARCH. INO. HYG. OCCUPATIONAL MED. 7 : 5 1 - 6 7 , JANUARY 1 9 5 3 . H I L L , E . V . , and CA R LISLE, H . J T O X IC IT Y OF 2,4-O ICHLO RO PHEN O XYACETIC EXPERIMENTAL ANIMALS. J . INO. HYG. ANO TO X IC O L. 2 9 :8 5 ,. 1947 ACID FOR BU CH ER, NANCY L . R . l E F F E C T S OF 2,4-OTCHLOROPHENOXYACETIC AC 10 ON EXPERIMENTAL ANIMALS. PROC. SOC. EXP. B IO L . MED. 6 3 :2 0 4 , 1946 ALL STU D IES WITH THESE COMPOUNOS HAVE SHOWN THAT THEY HAVE A MOOERATE T O X IC IT Y FO R .E X P ER I MENTAL A N I MALS. V E HAVE NO RECORO OF TH EIR HAVING PRODUCED S IG N IF IC A N T INJURY IN MAN WITH THE EXCEPTION THAT ONE S U IC ID E WAS CARRIED CUT WITH A LARGE DOSE OF 2 , 4 - 0 . THE MATERIALS ARE NOT NOTABLE A LLER G EN S. IT I S , OF COURSE, NOT POSSIBLE TO EXCLUDE THE POSSI B IL IT Y THAT ONE OR BOTH MATERIALS MIGHT CAUSE ALLERGY IN A FEW HIGHLY SUSCEPTIBLE INDIVIDUALS.* i MR. MARVLN BUGH PAGE THREE DOW1366922 - THE FOLLOWING IS A COPY OF A LETTER SIGNEO BY OR. MITCHELL R. ZAVON, KETTERING LABORATORY, CINCINNATI, OHIO, WHEN HE WAS ASKED FOR INFOR MATION ANO COMMENTS ON THE TOXICITY OF 2 ,4 -0 AND RELATED CHEMICALS ' IN LIGHT OF THE MAYO CLIN IC REPORT: FOR MANY YEARS 2 ,4 -0 ANO ITS RELATED ANALOGS SUCH AS 2,4,5-T HAVE, AS YOU WELL KNOW, BEEN USED WIDELY ANO WITH LITTLE OR NO DIFFICULTY TO THE PERSONS USING THEM. IT HAS LONG BEEN ACCEPTED BY THOSE CONCERNED WITH PESTICIDE! TOXICITY THAT THESE PRODUCTS WERE OF VERY LOW TOXICITY. EXPERIENCE OVER THE YEARS HAS TENDED TO CONFIRM THIS IMPRESSION. MY PERSONAL EXPERIENCE WITH THE COMPOUNDS HAS BEEN LIMITED BUT WITHIN THESE LIM ITS THE ONLY PROBLEMS I HAVE RUN INTO HAVE BEEN NAUSEA ANO A FEELING OF FAINT NESS DUE TO THE ODOR. THIS PARTICULAR DIFFICULTY ONLY RESULTED WHEN.TRANSFERRING LARGE QUANTITIES OF THE MATERIAL FROM-ONE VEHICLE TO ANOTHER. IN FIELD OPERA'TIONS I HAVE RUN INTO NO DIFFICULTY WHATSOEVER. IN GENERAL THE EXPERIENCE OF OTHERS HAS BEEN SIMILAR TO MY OWN. A RECENT PUBLICATION OF THE DIVISION OF SANI TARY E n g in e e r in g o f th e south Dakota s t a t e departm en t OF HEALTH WHICH REPORTED ON A SURVEY DONE COOPERATIVELY WITH THE U . S . P U B LIC HEALTH S c R V IC E ENT ITLEO ` REPORT OF AN OCCUPATIONAL HEALTH SURVEY OF AGRICULTURAL ANO MANUFACTURING IN D USTRIES IN SOUTH DAKOTA* REPORTS WITH REGARO TO THE TWO PRODUCTS UNDER C ISCU SSIO N THAT ON 112 FARMS SURVEYED 2 , 4 - 0 WAS U SED . ` ALTHOUGH IT S ODOR MAKES IT ANNOYING TO HANDLE, IT I S GENERALLY CONSIDERED ..TO BE NON-TOXIC AND NCN-1RRI TAT I NG TO HUMANS. THE LARGE NUMBER OF PERSONS COMING IN CONTACT WITH T H IS CHEMICAL WITHOUT ENCOUNTERING D IF F IC U L T Y TENDS TO SUPPORT T H IS VIEW . HOWEVER, TWO OF THE FARMERS IN TER VIEWED STATED THAT SPRAYING WITH 2 , 4 - 0 MADE THEM M ILDLY NAUSEATED ANO ANOTHER THAT I T CAUSED AN EDEMATOUS SWELLING OF H IS G EN ITA L ORGANS WHICH LASTED ABOUT TWO W EEKS.* UNTIL THE RECENT REPORT IN THE JOURNAL OF THE AMERICAN M EDICAL ASSO CIATIO N THERE HAO BEEN NO REPORTS OF WHICH I AM AWARE OF ANY PROBLEM OTHEH THAN IR R ITA TIO N R ES U LT ING FROM THE USE OF THESE H E R B IC ID E S . THE RECENT REPORTS DO NOT PROVE ANYTHING. THEY DO, HOWEVER, SERVE TO ALERT US TO THE P O S S IB IL IT Y OF OTHEH E F F E C T S FROM 2 ,4 - 0 ANO 2 , 4 , 5 - T . UNFORTUNATELY,'ON A NUMBER OF OCCASIONS CLAIM S MAOE BY C L IN IC IA N S , WHO ARE MEMBERS OF V THE MAYO C L IN IC S T A F F , HAVE BEEN UNFOUNDED IN THAT THEY R ELY COMPLETELY ON TH EIR OWN PERSONAL OBSERVATIONS WITHOUT ANY SORT OF CONTROL. THESE OBSERVATIONS ARE EX CELLEN T FOR THE PURPOSE OF A LE R - , : . - AS TO P O S S IB L E E F F E C T BUT AS I HAVE SAIO THEY 00 NOT PROVE THE E F F E C T . MR. MARVIN BUGH , PAGE FOUR DOW1 3 6 6 9 2 3 I AM REASONABLY CERTAIN THAT THERE WILL NOW BE A NUMBER OF REPORTS APPEARING WHICH POINT TO AN A SSO CIA TION BETWEEN THESE H E R B IC IO E S ANO ANY NUMBER OF NEUROLOGICAL ANO/OR HEMOTOLOGI CAL D IS E A S E S . UNLESS THE PROOF IS MORE SUBSTANTIAL THAN 1 HAVE SEEN THUS FA R , I CANNOT ACCEPT THESE CASE REPORTS AS PROOF. PERHAPS ANOTHER EXAMPLE MIGHT PROVE TO ILLU STRA TE MY PO IN T. AT PRESENT I AM IN VESTIG ATIN G A CASE OF PA RTIA L BLINONESS ASSOCIATED WITH EXPOSURE TO CARBON TETRACH LO RIO E. THOUGH THERE ARE A NUMBER OF CA SES IN THE LITERA TU RE SIM ILAR TO THE ONE I AM IN VESTIGATIN G ANO I AM Q U ITE CERTAIN OF THE ASSO CIATIO N OF THE IN D IVID U AL CONCERNED ANO CAR80N TETRACH LO RID E, T H IS I S NO PROOF OF THE CAUSE OF H IS B LIN O N ESS. WHAT I W ILL DO IS TO WRITE UP THE CASE FOR MEDICAL PUBLICATION IN ORDER TO ALERT OTHERS TO THE P O S S I B I L I T Y . I F A S U F F IC IE N T NUMBER OF CASES WITH T H IS ASSOCIATION APPEAR THEN IT MAY WELL BE THAT THERE IS A CAUSE AND E F F E C T RELA TIO N S H IP . T hus fa r I oo not c o n s id e r t h e c a u s e and e f f e c t RELATIONSHIP PROVEN. fcWE MUST REMEMBER THAT ANYTIME VAST NUMBERS OF PEOPLE ARE EXPOSED TO A PRODUCT A CERTA IN PERCENTAGE OF THEM W ILL OEVELOP * ONE 01SEASE OR ANOTHER. TO CONDEMN A PROOUCT BECAUSE OF T H IS WITHOUT FURTHER IN VESTIGATIO N WOULD BE THE HEIGHT OF IR R E S P O N S IB IL IT Y . P A T IEN T S COMING TO THE MAYO C L IN IC ARE IN A SENSE SCREENEO FROM A LARGE POPULATION ANO THE MERE FACTOR OF ASSOCIATION MAY NOT PROVE A THING BECAUSE OF THE WINNOWING OUT PROCESS THAT HAS OCCURRED PRIOR TO THEIR BEING SEEN AT THE MAYO C L I N I C ." I TRUST THE STATEMENTS BY A U TH O R ITIES QUOTED IN T H IS LET T ER TOGETHER WITH THE REFEREN CES C IT E D W fLL ANSWER QUESTIONS WHICH YOU MAY HAVE CON CERNING 2 ,4 - 0 ANO IT S E F F E C T S ON HUMANS. IN OUR OPIN IO N , 2 , 4 - 0 IS EN T IR E L Y SA FE TO U SE WHEN A P P L IE D AS D IR E C T E D . YOURS VERY TR U LY , j o / nem / s / JACK OREESSEN JACK OREESSEN D O W 712324 foot, \mc unebio to otan end would than cit or lio in an awkward position lull spastic limbs, particularly cnnrr^ci the hind legs, Other dogs stumbled and rolled on the floor in attempts to right ther.3alvs3. An occasional dog K. hao shewn evidence of irritation or pain whan thii skin over the back of the nod: was grasped. Seme dogs, when hold i crossing of tho Ijind limb3. A3 the n r a would show extension and of tho drug progressed the dogs eventually refused tho various offered. Occasionally cneos- ing, rubbing of tha eye3 and diarrb d, but not vomiting* Such symptoms were also seen i t survived a lover dose of 2,ii-D for lli (Jays (able 1). In th ,ho changes were relatively mild . and ware limited to spasm in tho hi c slight ataxin. . Harked symptoms were not obse: dogs receiving 2 t h t 5-T. iho .changes were limited to a slight t ' i' the development of ataxia, in the (tiffness in the hind lGgs, vdtlf .eiving the highest doses. Ho symptoms wore evident in tho one d 1 following a 3ingle dose of 100 mga./kg. (TablG l), . Patholetv. Changos observed were limitad to tils go tro-intostinal tract and lungs, Pour dog3 (los. l,2,ii,6) receiving 2,li-D and two (los. 13, 17) fed .2,lj,i?-T shoved mild to diffuse redness of the mucosa in the small intestine. In soma dogs pneumonia was present. Histologically the above dogs showed soma necrosis and inflammation of' the intestinal mucosa. Quo dog (lo. 13) had a mod erate, diffus hepatic necrosis. lYso clogs (i>'o3. 13sl6) had a mild degree of renal tubular degeneration. In moat dega that died the findings wore limited to non-spGcific changos such ay hepatic congesticn. In many cases death was prob ably dua to pneumonia which followed the development of anorexia, weight loso end myotonia* 15951 D O W 712325 a *-s 1,`w **r. nl-a** 20 ngn./kg. in divided daca3 telco a day produced death in both dogs receiving ' 2,1^,5-T and in one dog receiving 2,It--D (Tabic 2) Esnv freight. She only significant change in body vaight occurred in the animals that failed to survive the study (Table 2). Loss of weight in these dogs began 7 to 12 days before the death of the dag. General Synetons. Dog3 that survived tho oral administration of 2,I>-D or 2,i*,-T for 9 0 days were free of any symptoms. 3he three dogQ that died while receiving tho highest dosa of 2,it-D showed signs differing somewhat from those observed in tho acuta studies. She dogs : were quiet weaker end less responsive than normal, iiuscle tonus was higher in tha hind lego particularly on passive extension. !&ie hind lego viero held more stiffly than usual when walking and a slight ataxia was present. During the last 2 to 3 days of their survival two of the dogs showed difficulty in chawing or swallowing and eventually even refused a small bolus of canned dog food (usually readily consumed). There was also some oozing of blood from the guns and buccal mucosa. In dogs that died while receiving 2,It,5?-T the prominent effoct3 were weakness slight stiffness in tho hind legs difficulty in tho swal lowing of food an in one dog bleeding from the gums. KLood count His administration of 2,it-D or 2,lt,5-T did not have any significant effect on tho hemoglobin, rad cell, or total white coll count cf animals that survivod or died during the study. Tha differential count remained normal in the surviving animals. In throe animals that died a torainal fall in tho porenntage of lymphocytes was observed (Table 3) 15952 712326 Orr~"n weights. There was no significant, chants in tho ireight of tho thyroid gland, adrenal glcnd, heart, liver or kidney in animals that survived tho 50 dry poriod of study. In two of tho three dogs that died during tho ad min!stra tion of 2,2:-D thoro fas a slight incrar.sc in heart and kidney weight. A similar chcngo waa errporiensed in two of tho four dogs that died as a result oo * of Gross natholo^y. iVra dogs receiving 2,ij-D (Uos. 26 and 3U) (Showed areas of rodnss3 in tho duodenum, with 2 cna animal (No. 1*2) shoved a diffusely redc-cnod duodenum and jejunum end dog 1;8, autopoied on tho ?9th day demonstrated a generalized icterus. flicroeconic changes. ine heart, lungs, thyroid, adrenal, ovary or tastes did not demonstrate any significant changes. Three of tho dogs receiving 2,li,5-T and two receiving 2,ljr-D shoved an occasional area of focal necrosis in tho liver. This finding, however, was not related to oither the clcso of the compounds or the death of any animal (Table it) end was judged to bo of no signif icance. Tho duodenum of dog3 26, 3li, 2 and 1*3 showed varying degrees of hyperemia end some parly infiltration of colls in tha mucosa.. Hie auLnucoca and carcsa v/aro ncrmal. A slight Increase in the rvunbar of casts in kidney sections was notod in some doga (Table h) but again thio wss unrelated to dosage and is of doubtful significance. DlHUSSION Single large oral closes of 2,1*-D administered to dogs may produce Gigns characteristic of clinical myotonia. This effect of 2,2j-D was similar to that observed following injection into various cpscies^r^. In eddition, coma dogs shovad signs of irritation and pain when thw sk.in of tho back of the neck was grasped, wliich nay indicate meningeal irritation. Tha extension and crossing of the hir:d limbs, when lifted by the nhouldarr, cay point to a spinal or central 15953 D O W 712327 lceion. Other effects occasionally observed wero cncozir.g, rubbing of the oyos end diarrhea. The offsets of 2 t h ,5-T, previously unstudied, 'coro net a s severe, being limited to stiffness in tho hind logs ond etaxia. The highor doses of either compound produced onoranda and weight loan. Although initial effects nay be soon six hours nftor tho compounds aro given, tho syndrom developed slowly in tho dogs cud death was delayed, occurring several days after tho administration of the ccmpuunds. in tho chronic study, the dogs survived dosoc of 2 t $ and 10 ng. cf 2,1;-D or 2,1;,5-T per kilo of body weight without apparent ill effects. How ever, tho daily oral administration of 20 mgn./kg. of 2,1;-D produced death in three of four dogs within 18 to k9 days. This delayed death may indicato a cumulative effect of 2,1;-D. Tho signs observed in animals dying from tho 20 ngra./kg. dose of 2,ii-D differed somewhat from those seen in the acuto studios. With tho chronic administration, the animals exhibited chiefly a stiffness of the hind legs and ataxia, weakness, difficulty in chewing or swallowing andjoccasionally, bleeding from the gum3. 11 four dogs receiving 20 mgn./kg. of 2,1;,5-T succumbed between the 11th and 75th .day of the study. Toxic effects in these animals consistently included Light muscle spasm and difficulty in swallowing food. Ihu3, the chronic oral toxic dose for 2,1;,5-? in dogs seens to ba in tho same Tango as that obtained with 2,1+-D. ttith both drugs, there was a terminai less in body weight. Dogs surviving the chronic doses of 2,i;-D or 2 f h , 5-T did not chow sny significant change in hemoglobin, total blood counts or differential count. In three of the dogs (l/os. 6h> 57, 105) that died while receiving 20 mgn./kg. of 2,1;-D or 2,1;,5-T, there was a definite decrease in tho percentage of lymph ocytes in tho peripheral blood. Kill sad Carlisle^ have observed a fall lu tho polymorphonuclear leucocyte count in one dog and a decrease in the per cent of lymphocytes in two dogs rocoivLng 50 iagn./kg. of 2,1;-D intravenously' p'ar day 15954 702 MN069799 D O W 1 3 6 4 9 3 2 N ATU RE. V O L. 220. N O V E M B E R T ab le 3. c o a rc T m o x n r x x ju r ic r D N A on filte r N uclear D N A N uclear D N A N uclear D N A N uclear D N A N uclear D N A N uclear D N A "P -E N A c y L 2S 3 cy t. 2 S S cy t. 23X cy t. 173 c y t. 173 c y t- 173 I'o ia b e lta i *> E_X A c y t. 2 5 S m iL Z 3 S nn cy t. 175 mite 165 E N A bouod to filter* 932 647 912 971 507 865 ntl* C .p jn ., eom eted fo r background adaorpUon on to blan k Altera. F ilte re eo a la ia tn s 3 a o f nuclear D N A w en Incubated w ith 5 m l. o f IaheHad S K A to w h ich 6 M i n i . o f m (.KiUrf S K A waa added aa Indicated. Specific la d lo a e u n tle a : cytoplaom la 233 S K A : 10,020 o .n A L ta ; cy to plaam ln 173 S K A : 11.010 o.pn - lM . PcitothuTlibcnohlhriiiolcnsoptHrelowarepseoatlsraltDktaihntNgwrSAReathrNsovaAfistctueonwp.bupeacoroleerotooeftodipdulenabdnsyetosqna1u*e.ngnucrcael*netacrofmaroapmwleemtlhleeanstaUorSyn UInnsitviteurtseityofoBf iVoicehnenma.istry, EG.. WVnlTrOrHxABSP BBXEBCKB Received Septem ber 3 ; revised O ctober 22. IM S . * B o rn . P ., X ro o n . A . S , and S a tte n b e rs, 0 . J . C . 1L . In E le m e n te . P n p erl ie e and K w n d io n : Sym p. T b lrd M eeting 1 B B S (e d lt. b y Shusar, D .). 31 (Acadm ie Preaa, N ew Y o rk . 1M 7). ' Coraeo, G ,, M oore. C ., S an adl, D . S ., Groaacoan. L . I., and M arm o r, J ,, S e i n * . lS L 387 (1800). *Tew ad. X . X .. V oetach. W ,, M ah ler. H . S .. and M ackler, B^ J . U e L S to f.. 28, 432 (1900). 1Ylehhanser. Q ,, W in te rabe rec r, S .. and T n p p y. H -. J i eend I n te r n . B io p ty e . Con, A b a ta o t U S (1908). 1S in cla ir, J . H , S te re o s. B . J ,, S a a sb a vi, P , and S a b ln o w ttz, M .. S e in e r , 138. 1233 (1 M 7). * Sbapiro, L ., O r n n a n , L . I_ M arm o r. J , and X lataacfaoddt, A . X ., J . H o l. B ie L . 38, 907 (1988). ' W inlerab erw r, B ., B ie e te m B ie p tp e . B e . C Baw a .,28. 1 (1 9 M ); W inten* bersw . i - . In R e n m d T i t l e fh a cwm 'en e s B ie c k e e n c e t d e p e e te o f t t e B ia t n m u e t U ite e te m d r ie (edtt. b y Slaeer. X . C .. Ta*er. J . lL . P a p a . 8 , and Q tucH arleU o. X ) . 189 (A drtatfoo E d ltd ce . B a rl. 1988). *W lnteraberser. B , a n d T n p p y . B , B iet ie m . X , M L 399 (1983). * W toletabetew , X , ha B e n i i H m e t U e t e t U ie P r e eeee i m U it e e t e n d r ie (edIL b y T a* ar. J . I L . P ap a. 8 , q u a * ila rie llo . X , and S latar, X C .), 439 (S laevlar, A m sterdam , IM S ). ^ " Tlnaau, S . J ,, P re a lo n . B . K ., TItchanar. X B , and Lin n en e, A . W .. B io e t n e . B ie p tsn . B e . Cem m aa.,87. 406 (1M 7). W ln te a b e tta r. X , X . P t p e ie L C h m , 338.1701 (1M 7). " T u k o b a n . H .. P n w . U S S e i . B ern d . S e i ., 38,1088 (1M 7). yiam m , W . Q , B o n d , H . X .. a n d B u r , H . X ., B ie e tim . B io p tp e . A c ta .lS t. 310 (1988). >M o u ta o ch l, X .. a n d W lU M u a o n . D . H -. B ie e te m . B io p t p e . B e . C o m w n m ., 28. 38 (I960). " D a e il. X A , In o a s, 3 , an d O tte r, M . X , J . B e e t ., 88.1762 (1963). * M arm er. J ,, J . U e L B i e l .. 8 .20 8 (1961). " OlOaapie. D ,, and Sp4e*alnaa. 3 , J . U e L B W .,1 8 .329 (1968). ' B arn eU . W . X , an d B ro w n . S . H -, P m e . V S S e t . B ern d . S r i, 37, 382 (1967). " B row n. D . H , a n d K o vw lh . O . D .. B ie e te m . B io p tp e . B e . C o m m o n -, X L 282 (1986). " X p h ran d . B , an d H n tH e s n ir. H , C e id S p r in t B e r t e r S p m p . Q n e n l. B l e i ., 18. 78 (19<1). ` BphrnaM . B , an d I la k L T . P , N atane, M X 1*07 (1988). Q,, T a p p y .H ,a a d l . J , X . N a le r/e re d L .ljb , 133 (1938). 1 Y ileeyaaa^ . T , J . V e tU e m L S e e , 7 .1 3 1 (1982), . J . O . Jahah. H , and D es U n kt. P . P , J .8 6 .2 1 8 (1896). . J . C , Ja h o h . H , an d IB o n ln aH , P . P .. In X an ad T a k le m e n a. _________ _ d e m life o t t t e B l e t n u i t e t H d n k n d r ia (e d it, b y A O , b ^ n ^ L lt P a p a . 8 , and q sasttarlaU a, X .). 378 (A d ria tle a B o n d , X , an d X ro u a . A . X , In le d e r n . B e t . C p I tL (In tba penaa). " Tew art, X . K , an d W H drnen. B. O ., P r e e . V S S e l . d e e d . S f i ., 88. 309 (1968). Chemical and Toxicological Evaluations of Isolated and Synthetic Chloro Derivatives of Dibenzo-p-dioxin fbOtahecsnnatkoeora-vtp(et-crhdhyieioctxtkooixnxoi1ice.cdcncoBommmenpcpnofouuauancnetdodsari)takriineasonwh1ai,nt2gu.ha3rlas,y7lhl,8yiym,d9o-rpchorcoopuxbernrariicbenhlmgeiodcrtioohudmami--t ctcTuspsvpipdwcpdapwrhwacrhwmatb7shheeotohoonesiuyeeooyyyaeeheocifisabmeesmlATlmtrfdfcrinddbtsearroeuuorcuyiodtoohyteeerrrhlcroeenemrmm*rqnlhsouolee-oociniatriellybopucbiatnsnblnfepeppnieercwntpn.huisarelerescddcsuaroreercho1o.oeaeaoeelndseceecetti2romrletdaftccdrtaoduerio*li.rtiiir-simtmoRagieiatrccnwivtt5dogofmu.hodmiabeahlnlaraaoeeoimnllicsivasidteTtaecrycerntptsidtuwnceht,tsfadnidha,nhauoiehBecuoofeaacedirhl*oziielafrefmxleararchelufntuueakcruoiaabrtreiiavpctopfipm,nmnciutynvrcebs-tcotcduaanieatmehocpozadswroawelekurltensidbeetefoeei-erestwnnlefeotrtaanbeafdictaxnearctrihiatevnatnsabdrfhneiygtofailnefbpehcbsbecoyteportidannouetgleleytto'otitlorysxohgeorSnuopeolohdermtprlmduifniareucoEodraxcrinenaomurTuoobagn.*sicebssgoiotinc-asfrfrsbp-yieheatsronr5ienwi:iimcrenletaceihydadaldgdmoiiindT2donwrocasmnhqpbeoiirceuftit'ehgneanhrnlttoitaznimbo*ulhihm*coshenhteasatteseoowkceniaelfth*hamopsseesatdnowornormlnihiofaasshfosyttfoervtnxloroamoeahpttXirteocoeufhm,atehaaikorcwsmyreuximyhhfnopmcyebdcan*toeit-hfta.stiiroaehnnetfprhufc.ldn.ychcdftorecnnieelallmeh-.eoskoruatIdeusald'rdcnsheocrfynreswfemhngeferapueietaooderhTrspanddnaeoniwarptaaaego*tfianlecGeeovnhiscxtissatccrrguvtshmasntany;eteeeff2aieoeLttupethigmoniacoiiurc0wtshmcigdcsoCotreaiune.htfcraabrse0hcheintirhoucnelneadercbsroneaoaeeulrsuaestdsldiaoeprontpaxenoBhyadlul,pnwytinnnCeflarlahsfhrfusnaaralleretoyouateaemottoyommseeanntaaictxpirikqamaothoslrcnsiiantudtitehliaksunscurahuweeonanoryuguxcdbi(oefteseddlayslcr.GasefstmatitnaelfoswrniGucuddu*aetaprocaspttaLroanittriilrerattetrtectLrrolyrennateeClhhehooelmooodooriyiessCnyd1ld*dn*adeeese-s)rf,fff..,,. Tatis atL m m u T ir a a s u ia o ra x s a t m a m a r z i S a is p ii p y id ra a d * C h lc k m em bryo PerecatB e a t 200* C afoo M - b ln a w y p o o sa tst la p r m ira ii* Mil m ortatitr$ 2 .3 -D lcU a m p te a o l (X ) ) > 3 (T ) a x is H s ftttaea to x ic ta t cam - p o o ra ts 10 3*5, 6*5 2*6 8-9,10-0. l i t , 17-4, 20*0, 6*0 36-0 1*0,1*6, 6*6, 6*6 1-0, 1-6, 6*5, 6*5. 8*0, 10*0, 11*2, 17*4, 20*0, 66*0 50(H) 0*26 5*0 1*0 5*0 0*05 30 70 100 60 100 27 100 100 ( X ) ^ ta a e n t scads: (T lw ta cfa sic a l srada. t Jt> - (Stando* Us m s a t p eaks id s U v e to tlaa is tc a tia * Us m o f aUrtm . 1 1 a c a t o p.p.8. la U m s s - 3am pla la la sta d la to Um s ir ocU o t tr e e d (e rtila e ( 8 i before tsnalM U o*. S olvente n e i : e U su c L a t e o sa d cblm w fnw ortalttr a3 21 dava. T b t m o rta lity o f sea In k rtad ad 10-13 p e t oeavvcpaTopfoprpminremfctaareafneohofesieTiTlpIarrlniaxiedmub,soynicyskthecmtheariurtiuscanaeymnrdnaptmrahblrirttocwegewrcdeesdcllg.eaorceohi.cadhiipM.rthddouGrtl.hrsieretro.ohiitewusfmoionornoaLitufratiocimihdkHtaoteaiCaycethnilhputanlfceaaerae,y(bacprtttalt*dTteihviecoodtrldeodorhpodataaworggaeiaindogoiabbvlttsnfrrtaueu*irrpelnaapheetablaeese,etrdmnledlaeehdiiesamyresz11mantdo*nyt2iC*oh)aoooczowic,e,ptr.-se3a2o*fd2etadapfreebhr,,-,oecn1;7-3dadp3Aetbpedos0rad,,soi-,r84eyiom4ueedaxtcfoohpn-,oex,mione0aittx0pryortotcpetehuu-tori-orxdrmttnenatremeiarvdefnfireanccamnaaotoiietldkwebhrnocdrc,otprnaiaeah.gelfeetaneetocpaoloorldssgtyrhornmfatthfraioWhoalrfa;doctlcrrtoorddetotoaeyahfsoe.rahaidirnatrcotoolbmrloeeeiddhopaoeuanpbecnpnsierevTtmrhneuuthiaptcaeoiihnnihaztmraepennepkloernaorxeenaoodesnseftto-otokneomathiffnpthpl-ecloatsdkeo0r-pateiydaocxdn-mf^witp1trehrtsdiictpiiooyoeooslbheanihwipaealorrrlxayygiyd.aceo,ftcifcxpGidtdtaratcolnekmuroiytttterLettmooRhh.hhrmotlnmaltCny1ynyneeeeee--.. 15945 DOW1364993 .A NATURE. VOL. 220. NOVEMBER 16. 1968 703 rilriRfptt1paihikiDl2*ovrem>xecoCnsefmcwtuoer-tra2erlnootenttoGf0htshtinease0gexLeralc'hOceyCror4tacnoesrpeahpecnmfaimreldtce(enouarmt0cttdrhebrloh0oileneynyx/ecrncr8.Gadoimmeu0c2telLemu,adat3fdCmmozla,biex4tendanei,aciwni0rcpThbao-deeeottanferc*nabfide2ttnGztlrxu5cefoaah0ocrhcaM-a*2tamplhiro.CvvC-bleerdoeihdiTtftirnprryornohyaeoaaxpoepcmcithteaktdnociceteeyoooQtnwdtdremnmeoeo`eta.cwltepsrtetbcepoieirooItepdynmhesnepeeroxnb)iyorn1nl,a,ylat0eemymsatxpesupnmiioaadrsnsedlmetoioeerenplclcdwiacgeaoanutecernmbelenureadddyaet. TtM* x coxirsooCTxxxris.Sis-ontnianceiLrooxkonaunoioiumx mo tsn iDz anano-e-Dioxnr U x ta n O L C paak R * a* V n la ra la r S o . ot C l H . 200* C t U S Tabls X ate ixxtrsis xxo toe exbsto assar or uotarxs cosmxixts E a frre n e t to x ic fa t com ponent* C oap ooaata fr o m ch lorinated dibattao-r-O loxln and X 3 .4 .S -< a tn ch lo n p h u l pyrniysat* * t 200* C 1*0 1-8 3*3 5*1 8*5 8*9 10*0 118 17-4 20*0 350 7* p ercen t U A t 200* C m ortAlUj* 20 20 l* t 100 3*51 40 100 80 8*9 80 10*0 11*3 100 1 18 80 17-4 100 20*0 40 X /e 0*5 0*2 2*0 1*0 10 0*5 2*5 1*25 Par cent m o rtA litr 15 100 30 100 100 100 15 100 * f t ira s estim ated th a t ab o a t 20 m s o f m a la ria l n a lajected Into each e ss. t Sea footaotaa 3 an d i . T able 1, t Com ponent* fro m ch lo tln atad d lb an ao -r-d lo xin . O ia ria a la d d lb e n s o -V 'llo x la UtA-TatzmcbioCDpbtsoi nsamsta 1-8 3-1 8-9 10-0 11-2 11-0 17-4 20-0 288 320 380 388 388 388 423 423 3 4 e 8 0 3 7 7 o*ecootphc*acact(td2tcttco1hhcehe1xoTenhomhnvoyyiihJ4f4oeepetAoftTnePduu-ptdIrlemrdo*raar,Cofo8o2a*otenxao7aeraahs.1mrraplctt0tlu--e,psi2tmfclcea,oetfreoht4oiiiny.d8erirencot,t(oibhncohpapxaa,e3aneuca1s-Ootut5tlluilfCbedfh,ordrata,tthewnoooon,tmn-4eio--ohaerr2eetyerfhrslrrrfgdfitte-e,feecdgidpnoso,ooudpc16rhoipsr4arpthCtr,cootaerapdboo-twsweerecha-aaekiolinlcsrhesicmuchhascomshfteedtebbeiethpttvoeuhhoonketnia2aeirkcenireeinren,tembofxmudcpuesaceodo.pcunnioc3nohametabmshbrrormo3tuzzptehfrt,levoetmolwlsaebu7eroonorcirocoiooesdappodehsatcesn-dt-orthepebruurfrnoroeietraelhprmeordeoaimnlbiryoyrnptbelar2duibdoe)-nnioedycaipcnevrrdt.dckate^bneprtidttofioioeenh4iehontcciis,ouobteedoninonl4zetodaalzxhnoofsednrayihugboieoxot,ulnersoiinzshsau6Tsifneeroanc-monwsdoofs-osazoaga-pbnadashrmepLeioamitn-otsdts.hotr-iyzavdees)e-pytofxhaoda-ieetmn.dmhetitt-bpmebdmtitaldtannnhsrdibdewhoaiote-aiTmeo,cnrhusnemresiysndttaxTnetnThttxoae)ohealhipicefitrhia2,3iednthrlxmndlwncohietnropelthuohoe,en,wasieriihgxae33Aonribrein-.iecicralefnmoioip.po,disgdclseanh4nionr4tdndiimdu-mrneatepsdohistl.temp,hrsdfdti6nnmoenbi6fhrmbepnihrtahoriair8ce8-vptlsrrp-aeotagptrsataaiptiwntietseh76hiheoredoscsepnxrn.etrttoelatdae0l0tnehaopeagseniertciedaornlndtngnrsniletedamrmehcthTraachccplicbaiehdnirnotios,aecneltsmmthcmesoserdnaysllotpoopnhtjuh;opsedcipnntgob-e-omaeledel*moerte1toodpcyotctortf8atoatibecvpfchethhwrtmabrorrtIa6kfmhx(itoyrirtoraoniaeeTesor123nbrsoouoshpeopeppmuifniruti,1,n.oodrtbmonpifh2h3nrfhemtziamb,pmcmteahaufoao,y,e3lenohttw74miriaor8btttntnirnwn3rftfet-ri,,eehehohc0ereoaaloot5d8o-npoot0arddoynohhae*en6nedess----l.l-lf-ff pmvdpfdcntitpftRMnfsurptcshaocW(taaooiaeaeiuloreiueeuieishaonifeooembocdtctrsgrgerWftrnrrmeaRraodarysnltpdbaioetiihdgartmiseWocichrcenlaesuotrelebnoceekaiaariadiiiolfgcnarifJqohafntaseagsnianrerciottlohllitdwumtndnrltdesih,ripddaalsdhroeroaneisiatiBitlacrneooharosduarniuunnhlvosfhtresvtomrfdefappn!fOm.ambcauoeatakdldaieppr/auoanekasel1tcwptuortlomhtunot2niFrrrodthoofarWcyarf*ofteeyticcmapdfDpo.utpio-nhtttpnohseacrcoiiedy8itbdnreco.Sheaaeo.rhxrlcnooatemi-liorurodoso(ectoqcv9itnoceoglkaSsetemJorocnibe.rmeou)ciinehdlwtsdoroin.dootmriridhiritoroemmspsaoseretsg-cscffwiotwl.s,oleheT.CenrocraiearJeihacesfcdfTlteuitkuttasraaruuooanhrataehanmacTdyplhmrhoetfmmnscttdlodpooeitecefeoheqrmhh(atiditpeodlceemmlhntaMeulcoleablCoosdeoeblmssifocyieariedforewasaeeenefnhcrerkcpfdlrrrrptsetvnaShmonselocotaeeoicerrdyrontedntentitt1apnwtesormiuMoaostouinartxi2igirp,blayodlindbladpixhle,yeeqadf.fnaoanfnleDeoutriynecascuflvorrhncodanatsmiarhbctathtteyaeausrthce,otsgzdbltletltbhnr,lcganoiaoooetehtiueHueDdDpetantyesrndrr-nwrcrpceceisiLsdleysopodnhyt,othlurrstc,cv.meifiiso-priselgM.ntislelohvdooo,toawhhcotErottteaasamiysiitinhrleoicAuerdupodrnlnyTnlso.asdhitednlrsmlptxpuidndas-usafhsorle.otodEawooaoioooacbdaotofhwhieinlfurirtualtretrtrgiTap.rhwaoe.gelahhtecetcnsoechpieinnuhha.deeatseRot1ocdrooareFthsnu)oneilp2rrnhmisfsldmauef8*irielrcfiotbaoiposibktdyea-mbr2aelsichfipl9heawreahisncvinoej,rkc)Ayooty3sepsbhwedcawsmtaoiii.cwlcupd,cedndeolodoilcdle4ftooooouutencdorfrsoefnMoemrhid.eooornrrnort6mehitdalnolsardiaikesonhkys--rs-,rsr,l. JQJADAAo..amhcDRvxnqi..xdaCRHxHFeurimaaomxasuansmarroVreooukizrzneAxKr r py*pWfiitsnooohfeoo.ejfTaednfsumaerlcektahaen2cyorrtatcnbeete,i.meha3emtnhatsderecsdo,rtipT4erooiefcaoimiia,shrrmana0nrotfoteliopaa-tcmppssofttxtratioeehohreutnilatnietnedtccrrrnhchnuaeeeeotgefmeocnsliaoiGfaolauhtccnimptstnGLllxhh,ipotrostCisliLyetruxsontfhoprhCcaorrtsraoepaoaueeril.tnlahecrlsrpyclat2eateeeehsbsiTtw0stncoadiahela.0hvotokentodseeelerbriwdeisadACfpyn.wdgrrniyemaeobaaaoperstaimensTtfrreoontsneeedidhlucmzpytTotehnsrbhohasdofuaarty-eareaisoutbgpibatesmtmglge-teoorhdwediheenolfvaweifsae3zfouteeteirtcieoo.rxnnegoshregG-tiddttehmpihTnnsriciLtma-aacvchkedoCpnnetoieeanoidfhaoomntfodfutqelrmxorynaempasu2oisxnesmlnaoa,amaeib3dt,nmcnclbheda,ieao4trreztstpnifniym,hbhexet0aaltdyoyededeasl-t FaWBDnoueadorpsedahWariautnenmglodftefaonDrSnetc.r.oiuDefgnCHcA.ee.ddmlthin,iEstdrautcioanti.on S e e a ria d A o e a a t S ; n vfaad 8 eptm nb*rt7, IM S . 1C A en. S t - -Y o n , 4S. V - " ' -(1 M 7 ). Abmtr.. T o rn !a . )*.. (Teds. 3., ana K ariaad s, X -. ra ta y e A e U m U , 7 k 1 M <1MSI; CUm . U , I S ltd (1M B). V e rm tt, 3 L J .. lU r ila e . J .. an d U s b a s h lla . J . i - O JK . A f t . C U r n iM i. TTc4si7,.r1..00J3. (A1m94a4s)..OJW. Atmi. CUwmwtt. IX 133 (IMT). O M cim i ittU m d m o f J m Ii i h , 10th rd .. K O . W .0 8 7 -M .0 9 I. (AaaocU U oo o f O fficia l A g rico ltu a a i Chem lats, W u h ln fto n , D .C ., lM u> . W o o lle n . J . C ,, A rt m an. .Y. R ,, and A k s s n d a r. J . C .. J . A m m . O f c . A i r . C S r m iM i. 43. 734 (IM X ). 15946  D O W 712320 H N062 33 4 ACUTE AND CHRONIC TOXICITY OP 2,4-DICHLOROPHENOXYACETIC ACID AND 2,4,5~TRICHLOROPHENOXYACETIC ACID IN DOOS Victor A. Drill, PhD, M.D. and Tomiharu Hlratzka, M.D. from the Department of Physiology and Pharmacology and the Department of Pathology Wayne University College of Medicine Detroit, Michigan <i x i This study was supported by a grant from THE DOW CHEMICAL COMPANY 1594? DOW 712321 Both 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5trlchlorophenoxyacetic acid (2,4,5-T) may act as plant hormones and herbicidesf> 2 > 3 >^ and are now being fairly widely used for the control of certain types of weeds on farm land. These herbicides are being sprayed from airplanes on many acres of specialized farms and grazing land. They are present in trademarked preparations sold at retail for home gardners. With the widespread use of these herbicides, possible toxic effects are important as accidental ingestion may occur or in case food residues are inadvertently encountered. . In an earlier report 2,4-D* was mentioned as being non toxic to animals and man when administered orallj^-^^). The in Jeep ion of large doses of 2,4-D did, however, produce symptoms in j animals which were similar to those seen in clinical myotonia^. More detailed observations were reported by Hill and Carlisle who studied the acute and subacute effects of 2,4-D in various species of a n i m a l ^ . There are no reports- -concerning the toxic properties of 2,`4,5-T. The present study concerns the acute oral toxicity and chronic oral toxicity of 2,4-D and 2,4,5-T in dogs. J.-'v 15948 METHODS Adult mongrel doge of both sexes were used. Most of '.VTOVI the animal*were housed In the laboratory for a period of 2 to^.&-^. 3 months before the study was started. During this control ' v Vr^-vy..^. period they were immunized against distemper with the Green vaccine. The dogs were fed a standard stock diet (Priskies) ' ad libitum. Both 2,4~D and 2,4,5-T were commercial materials - r^ with a purity of 98.5# and 98.9# and freezing points of 132,8C .. and 15 0 .6C, respectively. * :: r^;%A In the acute studies the calculated dose of 2,4~D or 2,4,5-T was administered as a single oral dose in capsules. The dogs were observed for a period of 14 days at which tlme^'v^C^-av)^. survivors were autopsied. In the chronic study the 2,4-D or"* 2,4,5~T was administered orally in capsules, 5 days a week over a 13 week period. Each capsule was imbedded in a 4 to 5 gram piece of commercial canned dog food, which the animals consumed readily, thus avoiding the continued trauma of the stomach tube. During the study the animals were weighed twice a week. Control blood counts were taken before the administra- ... . ' . 4' - . tion of the drug, on the 30th %'A... ^ 15949 D O W 712323 day and cu tho ?0th day at tho coroplcticn of tho study. Hemoglobin was dotominod with a photoelectric colorimeter?. Upon tho death or at tho cera- plotioa of the study* tho animals wero autopsied. Tissues v.ero taken frora tho lung, heart, livor, kidney, adrenal, eploen, thyroid and ovary or testes, fixod in 102 formalin, and stained with hematoxylin and cosin. ' in su lts 1 asu t: c p j l toaIC i t ? . "ortal!tv. Tha effect of sizigla oral doses of 2,i;-D or 2,1*,5-T on survival for 11* days is shown in Tatlo 1. The deaths wore delayed and occur red 2 to 9 days after the cosmounds vero administered. The oral LD^q of 2,1;-D is approximately 100 ng/lvga and for 2,I*,-T is in tho range of 100 egra./kg. or hicher. Body l/eight. Tha large oral doses of 2,I*-D or 2,l*,i?-T produced a . C decrease in body weight (Table 1). Such animals developed various degrees of ' anorexia end thoss that died refused even canned dog food towards the end of .. their survival. Svr.ntcr-3. In dogs that died the effect produced by 2,i*-D varied from a nild otaxLa end stifflisss in tho hind legs to a definite myotonia. Initial signs wore often noted 6 hours after tho oral administration of 2,1*-D. At this time tho entrails were raoro quiet than normal and a slight ataxia was oc casionally proscat. Tho hind lags wars always affected first, the forcings later or not'at;ell. Thora was usually a progressive increase in spasm in the hind logs associated with increasing ataxia and some dogs spontaneously oxtonded the hind limbs in a spastic movonant lasting a few seconds. The knee Jerk was either normal or hyperactive. In the early stages of acuta poisoning with 2,1*-D the animals vero usually quiet. If tho mired was lifted and rado .to walk t!io spasn and ataxia wero clearly noticed, but whan walked for c uhilo tho spasm and ataxia tended to decrease. In tho lator stages of intoxication, tho aniiaal, when plccod cn his 15950 for g lx days. Repeated injections into alee did not alter tho peripheral blood picture!?). Large doses of 2,4-D intravenously, or in tie present study orally, occasionally produced some necrosis in the liver; However, repeatedly administered oral doses produced only a slight and inconsistent focal necrosis of doubtful significance (Table 4), Deaths during the chronic oral administration of 2,4-D or 2,4,5-T were not correllated with significant lesions in the liver, kidney, or other organs examined.' 712328 oo SUMMARY 1. The acute oral LDj-q of 2,4-dichlorophenoxyacetic acid (2,4-D) in dogs is approximately 100 mg. per kilo. Doses in this range or higher produce a definite myotonia accompanied by anorexia and weight loss. The acute oral LD^.q for 2,4,5trichlorophenoxyacetic acid (2,4,5-T) is in the range of 100 mg. per kilo or higher. Such toxic doses only produced signs of a mild spasticity. 2. All dogs survived the oral feeding of 2, 5 and 10 mg.'per kilo of 2,4-D or 2,4,5-T 5 days a week for a period of 90 days. These doses did not produce any symptoms or changes in body weight, organ weight or blood count. 3. Three of the four dogs receiving repeated doses of 20 mg. per kilo of 2,4-D died and all four dogs receiving 20 mg. per kilo of 2,4,5-T died during the study. Toxicity to 2,4-D at this dosage level was accompanied by bleeding from the gurus, necrotic changes in the buccal mucosa and some diffi culty in chewing and swallowing but only little evidence of 15955 OVV 712329 clinical myotonia. A terminal fall in the percentage of lympho cytes was observed in three of the animals. 4. Death during the repeated administration of 2,4-D or 2,4,5-T was not related to pathological changes in the liver, kidney or other organs examined. 15356 QZTL MOQ Effect of single oral doecs of 2,Ji~diciioropheaoxyac.ctie ; acid and 2^4,5-trichlorop]w't'iioxyccnui,c acid in docs Dog ' '< Wt. No Doso Iocs rii/a lieu IF 2 :1 3r` 1DI 5H ti' 7F fi? . 9? 10*-' IIP 12M ifJO Loo 2p0 250 2?0 1J0 - 100 100 ICO .25 25 25 -0.1 --0 3 -i*U -2.0 --0it -2.5 -2.0 -1.7 --2.1i 0.0 +0.2 +0.2 Svnrvtonn 2 ,L -V ++ -<-T*r ++ ++ V 0 + 0 0 0 0 +Dlod Mortality cay 2 2/2 3 (J 7 3/3 li s 9 u9C ' 2/U s S 0/3 s I3H lid! 153' 16? 17? 1EP I/O 2DII 21? 2211 LOO 250 . 100 100 100 103 50 5o 5o 5o -1 .1 -i.ii -0.5 -1*0 -1.0 --G.l> *0.3 -2.3 +0.1 --0.6 F# female; H , ir.ale 2 1/1 *r 3 1/1 0s 0 0 7 l/h S 0s 0s 0 0 s s nU//hU 0s + 5 survival for llj, day test period. colunn indicates cCT^sral severity of symptoms as discussed in text# Os no change fron nomal V/ <V ` ,s * Vi* - ` c o1 > 1 f)' 15957 D O W 712331 O Body uoiijNt m d survival of do3 fed 2,1;-dichlorcphcnortyccctio acid and 2,It,5-trichlorcphci;c::yacctic acid for ;'C dr.ys / No. Dose n t t Init:al V aria 23? 2iiF 251 26? 27M 25F 29U 30M 31M 32H 33? 3W 3SH ... .. 36? 37H ' 36? 39H IsOF ld.ll k2F hy.i hh$' h6F h7F Bn ncvia noao 2 2 5 5 10 10 10 *20 *20 20 20 none none 2 2 5 10 10 10 *20 *20 20 20 ill.9 9.3 6.6 15.2 ' 9.5 12.0 lli.7 11.6 17.2 13.0 9.8 12.2 13.lt /O 12.1 11.3 .8.9 8.6 12.3 12.3 13.0 .9.8 11.a 10.5 lu.9 10.9 i Wairht <*.,r1 * * 2,11-0 ILcj4 10.9 9.5 13.8 9.5 12.5 11..G 11.9 17.8 . 13.7 ' 5.9 10.1 9.7 2,U,5-a 7.7 Hi.5 12.7 10.0 8.1i 12.5 11.5 . 12.2 9.2 9.2 . 7.9 12.7 e.2 l liC +2.Y +1.6 +2.7 -l.li , 0.0 +0.5 <o.i +0.3 . +0.6 -0.7 -3.9 -2.1 -3.7 *O.U +2.U +l.li +1.1 -0.2 +0.2 -0.0 '-0.8 -0.6 -2.6 -2.6 -2.2; -2.7 Day Died ; % 5 s s s s s s s s s li9 18 ___ l ...... a s s s s s s s s li? 75 li 59 F , fecaloj 11, jcsI q * s dally dose divided end administered 1/2 in-A.11., and l/2 in P.H. S a survived 90 day test period. 15958 DOW 712332 intic 3 Effect ofA 2,ii-D md 2,li,5-T on hcncglobln, differential counts total blood and Dog Vo. 23wr '3or' 3'ii-i 3vi W 3bi 35*i " Doso Day Hb rag/iC RDC r.il. wac _rIV?_l"._U'tV_y___Lv_:Pn.l~fhforenitoiacl count das ioein ( /a > Co:itrol Dogs none 0 u n o 5.72 17;C`00 5e 3d 0 30 13.C2 5.93 15,600 6li 29 0 9 0 13.70 6.09 13.350 71 27 2 none 0 I2.L0 .Oi fs\j\J CO 11 3 30 111.72 6.65 13,150 7? 12 7 90 lli.SS 5.15 7,100 79 21 0 none 0 9.CO 5.03 15,100 57 26 1 30 10.75 5.63 13,300 56 16 2 90 12.7U 5.E2 111,700 81 1C 1 none 0 12.29 5.53 53 39 30 13.31 5.78 114,900 63 '26 2 li 90 13.95 6.U7 6,lioa kS 51 1 2ct--D *20 0 10.1i3 3.02 13,cOO c li 2? .5 30 12.U* 6.16 15,1x00 66 26 li 90 11.52 6.35 12,100 70 25 6 *20 0 " 13.18 '5.5o "ili,850 5Ji 30 111.1+6 5.88 9,700 h i lil li 2 li 9 111.36 5.6? 16,600 79 IO 0 13.20 5.72 15,200 59 Ili 7 bi; '1Cr.p 20 0 1U.9 .Uli 13,150 75 II i 29 111.59 .3li 9,100 68 27 li 00 07 00 00 .0 2 00 0 03 00 0 ii 07 00 0n 0h :0 0 0 3 03 00 05 0 . 12 01 i-'oath aay " 1.9 16 25 ii5;i *20 0 12.5U 5.35 lo,2)00 72 30 8,6U 3.98 I6,li5b 77 1*9 3.93 3.07 6,900 9li libi;1 *20 0 12.Ui> 7713"* 15,060 3 30 111.66 6.82 11,200 71 un- 20 0 12.UM 5.73 13,di 3 l|C*i 20 0 12, U .Q3 .l,o00 51 30 12.93 5.81 111,650 78 59 11.97 6.11i 7,175 92 12 13 li 29 23 32 hk 18 9 5 0 10 30 7 20 0 20 00 1 il 0 1 20 li 0 3 0 10 0 L9 75 11 59 F, fcnaloj M, male * z daily dose divided and ediainistered 1 / 2 in A.M. and l/2 in P.M. 3b conserve space only data on control doge and the highest doses ai-a given. 15959, N liictoloical dhnjc in livor ond kidney of do(?s fed 2flit-D or 2,U>5-"(,for 90 rieys Sa LZ O sta Cq ? OJ HhKoUe*r n(>X c. o Fto* enr o o 4 t-* r4o- IUi 4- sn. fcrd-OrNeV-yiif-ut-jfIro-thr-ot-vui) ou>oo-o> OcrjI oM oMoMoMoH Ho vnvnro io aO13 aO WU UlV*W>\H1 W) lo MW-Mq fCOrvMCnM.c~cK.j M MM oMoWoM oH oM of vnvn ro ro aOl>ao c'OnU-To.VirO- l i l i l ) i UT.S S f i t t i l i) 2=c8q .oc?a rtotl -V' HrH O+r o o O O O O O r+o+H O +H O O r+o H+ O O O C r%ro i*r- fO >~3 o o y Ci Coi Ht"** OJ U HO- Q H + H O 0 O Ft> O 0 O O O OHOOOOOHOOOC . + > VH)* a ! O H o 0 . 0 Hi to O O H O O OOOOOOF'OHOOC * < OQOOOOMOOOOO O O O O O O H+O O O O O &Coi rUfr ua i.*) 'i -;asi>*yy a V. tV: * V v' Z T L MOQ 0.86ST D O W 712334 1 Hildebrand, E. K.: War on weeds, Ecicnco 103 U60, l?ii5. 2. VanOvorbeeJr, J., and Yolez, I. j Use of 2,I;-2ichlorcphcnoxyactic acid as a falectivo Herbicide in the Ironies, Science 103 1*72-1*73# 19i;6. 3 Snith, F. G., Hcji-sr,. C. L., and Carlson, P. F.: Control of Ragweed Pollen Production with 2,li-Dichloroyhcnoxyscciic acid, Science 103 k 7 3 -k 7 k s 1 9 k 6 . h . Earth, P. C., end Mitchell, J. V,: 2-li-Dichlcropheno:r.'acetic acid aa a Differential Herbicide, Eot. Gas. 106 22ii-232, 19iti.. 5. Euchor, U. L. R. Effects of 2,H-DIchloroph3noxyacctic Acid on Experiasntal Anircalc, Pros. Sec. Expor. Biol, and Mod. 6 3 : 2 0 k ~ 2 0 $ , 1 9 k 6. 6. Hill, E. V., and Carlisle, H.: Toxicity of 2,i;-Dichlorcphanoxyecotic Acid for Exceriuental ^nicals, J. Ind. Hyg. and Toxicol. 2 9 : 8 $ - 9 $ , 19k7. ' 7. Evelyn, K. A. s A Stabilized Photoelectric Colorirseter with Light Filters, J. Biol. Chea. 116: 63-75, 1936. 15961 an j * l Toxicity of 2,4-Dichlorophenoxyacetic Acid and 2,4,5-Trichlofophenoxyacetic Acid A Raport on Thair Acut and Chronic Taadety in Doga VICTOR A. DRILL, Ph.D., M.O. ANO - TOMIHARU HIRATZKA, M.D. OETRorr 1536? Reprinted from the A. if. A.JaAnrucahrivye1s9o63f,InI'duul.st7r,iaplp.H6y1g-i6e7ne and Occupational Medicine Copyright, 1963, by American Medical Association r TOXICITY OF 2,4-DICHLOROPHENOXYACETIC ACID AND 2,4,5-TRICHLOROPHENOXYACETIC ACID \ A Kaport oa Their Acuta and Chronic Toxicity in Dog* VICTOR A. DRILL, PkD, M.D. AMO TOMIHARUorHrIsRoArTrZKA, M.D. B-i- A lWa2antafafMahoascn,ron4eoeiuidordat-drtlrhDaOceeby.emacadpdTatnudwdaohdinntdInHnedreeeigdntdntsaaaoewwt(ss2rainalr2cupely,ihalnieo4d,brmel4dan-pieaunnd,yeatscrc5sogieoapleeuec-saxesrdbrrdtThdlneeisesipcltm)anieefofiirnedroortrtorimofgyvonnrfdimuarnepiautaetstsmchhyhincptettoeaeeeesdraoanirnadoyrretcoscocdopftdtfo,hxoexlswaatnyry2cmih2oonsctacm,ee,rr4neauc4roapspp-sreier-ellDclkrtDtlaooiyooorcnhomppn.eirfutrenrwepaasrerc'rhmoddlbaevpteorisssidaaartetdniiotenrrdmsaHndimxady(uoioetii2nooeuielcsnafoa,bwsnis4,ecrttny2tyy-esrmpissD,eopvtp4ooHosaaenees)s,fnys5reociso,tdld-ii2lahlbfoeTbd,ntosfle4hh.aasedsae-epsnoewiDtrentfd2Tboeicbasr,inaexha4ieceddaCndjnie,eitvelcn5dsaindaicme-zigeprtlrtoeesli2rratiifnodineefsn,lf1c4snonlseohe.aef,frctc15nalalnntoloy-tshrirTwdtfonTmrmoohihxeasmlcaspetnoriaiarucnlehrrceelaadegeosnndyteinmgtundomhoduoaonsagycddrxpw.tvosaodgioeyoe.enntrersardobaeiceTntcmbnzdesaeeheeiiirntarnntaeehnisoitl.gnngycs,s.ef1 E X P E R IM E N T A L PROCEDURES flcmeaoadbntoAetrarrdoaialtusolltpstra,yenrmwdifooaiotdrnhrdgtarhaesepltypouedcrwrokiitgoeydsdreoieofoitfmf96(mbtFwJourtoianhsnilzddtseoeed9xs8t)eah.s5gr^aea6dweineaslmrntiebdodintiufustrshmteeesed.mz.bipnBeeMgfrtonporhweostiitn2thoht,s4fet-hoDtefshteu1Gad3nrayZedn8einwm2ana,av4sdl,as5cs1-cTtw5ian0er.etr6we.edeCT.rhhe,oeDrucesduosepomrdiegnmcsigtniewvretcethlihryaieesl. oralIndothsee iaucucatepssutluedsi.eTs,htehedocgaslcwulearteedobdsoesreveodf f2o,r4-aDpoerrio2d,4o,5f-T14wdaasysa,damt iwnihsitcehredtimase athesinsuglre- JRWmHP(S-drca,eeac)igrunyecbptTZsFXnLn.MaiiAccrhleiSoMiei*HB(YdAsmoaUrleu!itic)ntsl,hlnct.Plitetth,tmiuBhH4osvEeedU7tEaeoiPr-xylLZl,re.cd.DpssaN-,ee:icV-G4etrCbrJyU.paP7.ar.,sa,aLm3rsBCrInoaes,.tnaindoudmo1odnR1d,lpuL#lfu9depce.E4ns2t:Cgo6tiSt.,M.eor24c.EatoMn2r-eHfoi(lDfMd4ftiefcyes-w.iP)2:hlecgcbeMhid3eth.yWt,sSl2y.hleloS,ms,aHdocari2ifo1oirgcj.t:,9Tlp.hi:42ro4no2hoa,-,4geT40nDeWnx.y.F4-niotiD-Wc.acx2a.fcxhi:rn0Gicleyioa.5dohea2m.t,drl;Myc,ooP4se1rHp,hd-9to:ohDiai4a8pcSefe6rm5ihcmac.A-2Deioh9ne,andx54loencoa,ydr-cwoxr,Deao1lyacoiC9pCascelg4hchth7yaieelec.1JontmiaS^irac4Anoxei6cdplayAdea5hnadlc-tdedc4ht,nCdei6evatC3oSiexoc,mDacyaHri1epaelA9sepcnaEo4rneacd&bnxtyerdii,tp.ccme1(Rir4daMeAi.s)enmdtFsievda4n.ona7:fntt3faDho-PlC4eOria7foAtvfT4hnEeen,rotrxorirelmbopp1onel9eigatec4irlyaoka6si,lf,,., I, 1MW 2 4 9 5 0 4 2 paowuhvtdoaotr4poyaVeiloeeHrdct.itrKeTiscit'se9sc*ku(o,bdeklolfsioi>rgxdoiowmseadfdeyaefcrttaioehewnaroremtt.eln*a1eaertk0takdtho%atUemwoshdpveoefatcoeorrcgornecarhmmhmaftdropaato1eouklltneai3dbhentit,eenich,wo.wnalebsuonheDetnurkdifocugodfhap,rrsieiettetnhat*rhhetgiitenhohaeteedrethhdts.*e,atecmudEwlod2hmmsmaiy,rtt4ceuhi.ph*nrldlo,0ieyhcHiktteacirioeoomptdamhnnrsntaekuseot2wuoloygea,mfx,4lnowyo,eait5bmdlfhdai-ineTrsnaterhleinsasemvwaatnudldwdhausdiarf,leyAuyers,oa,gdetpsde.ettlidmhntehwoeee.nnhirnonmrr,citsaihahwtnthveae--e4yordde3ritddo0oitiiwwtndhoSigi,wrtcdhacaeetalmnhlryydaaee,. TaLx L--E fftct o2fASJi-mTrgilctklOorroatlh*D%oiot*xyaocfti2icA-ADcicidMomroDpko*gm*o*yacttic Acid and Doe***- Doe* M r/* * -. 1 OOOWOOWO0WWOOOOO M L ....................................................... I P . ....................................................... 4 I k ........................................ .........- S M......................................................... 9 YsMovvsosovovvooosistssv*# T R . ...................................................... s r _ ........................................................ r . ........................................................ r -10 .................... .................................. u ........................................................ 1M L ........................................................ 1S 1L . . ................................................... M IL .................... - ........................ U I . ........................................................ IS V ......................................................... n r ____ . . . _________.. M * _ ...................................................... U K ........................................................ U K ....................................................... SIF u .-f - i i . - r r - i --------T - a s ......................................................... 0 400 no no SM 1 ao 100 30 a a mo m m m u* ua a a- am w siebt Loo* S r . LSD -< u --n - 1J --10 -H U - --u --10 --LT -U 1 10 + 0LZ +M SAM ! --1U --L I -O i --LO --LOT --L A , +M -a +L1 --0 m to m t ++ + -H -H ++ + 0 +- 0 0 0 0 + + 0 0 0 1 D ata D rt t 1 r 4 8 . as s s sT s ssss M ortality 1/1 V% Vo w VL 1/L . VO VO *taS-fc-oimtaeael--M ta ra-- Sm mrvmc iSs w day tom* C am nrtoit. m m th M . oaw a u e u iilM is o n u l SUITS I. AaUrOraLTuncityj--(a) Mortality: Theeffectof singfctonl doses of 2,4-D oa2,n4r d2 ,o4c^c-uTrreodit,twRuttrhwjtthekftjHiuniqifjiopusrfdro1auf4yi1ncd0sa0aly!fmsltyigs./t1skh0hge0o. wcomorsmghi:pni-ogpTuhenerardb:kslilwo1ge. rrTaemhaed-omdfeinabitoshdtseyrwewde.reeTigdhheetl;aoyfreaadlr rthat di(eTdarbelfeu:s1e}doervSaeulncdhcoaasnennsiemdoadflso2gd,4ef-ovDoedlooptosewd2av,r4da,r5ito-hTuesepndrodedgorufeceetshdeoiafr 4 Evelyn, JC A .: A Stabilized Photoelectric Colorimeter with Light FQtera, J. Chem. U ti63-9S, 199&. 15964 3 ,-~*, ;. aaalomwenffgpediteslerrwdronse(wocgamsnm)erteoearoceestxSroeseidynadiavoldmqwsegasuip.snaxiiteyTdnsohtspchmsotroethaeuisnfaafr:ktffnssaennenIcaeennetefsioenotsdredjumeirsosnfrplgtaikyharslt,sehswemttaexho;antrahstdeiahtninleneaddiadttiehfsdheodllemdeiergregthithhlsnhneitenieogtsadorshttemriaafalnlxfeaatdeigildtoaceselontrifwmraipoonsarbhfsirostsyo2ednpoc,iu4niceomac-crttaDeayaeacdsod.sttitiopAbovwanayneltasli.it.ltat2ilhhyc.,T4ishpI-minDertnieirocmtseivrveaeeaenlwa-rmttsis.haeieisnegTdngnthasufanler-astoiauwsmhmtxaiiealinnrlaldygaes, ; ppooitsuqnInontfbaapuoaxirsitanntfetiiebhItciocdtrtcyn.eewoev.uedamdetlhflI,tnhdaaffhepbeod,terneettlcufshbystfrwttseeheushtbaoraoottoeaefyaruutnndflgrlelsysdio.idetkrmpghtseiasithenOrathvtosstalemohcf,dogtwnmcahivrwenaoudeaesisstomtfgsroiiwiuotontxlstphlanigfheodiflreac.eltkroavelasehlgcdebtlhydiiiusrao,oenea.tcfwndesnsokiAs,nndrlepnteeoedhaomaxegf,eoznitswasteic.thaodnnhachnengeOswaeiilii,smetnonktido,hogenrwaonutecwlhgaa,krabwserlanwbddwilddisektohnhpvao,pgegcasegosntrs2nhsogmoss,teip4surthtflusia-aosaoaiDmstplcnwnnhplea,gydbeeedswlddtmeoarheo.iedftteeynafhaveutSaxnhisiansoitdsd,eneasdmpediaaatnmhfeernestciotnataendehdilxdltdcleso,eoiedgawdlfdlvwiiismamaawi,otrerrsonbrwbeririohseursdthteu.aenheemtsauacAecinbsroaltseeuwflrynhelaakapoetesrlehoeotrllledoyydeesrr. l1i4midSteaudycshto(sTsigpanabsslmeweo1rf)e.thaIelnsohitnshediesnleinginsstaaonnncdeeadtohsgleigtchhhtaatantsgauexrsivai.wveedrearelolawtievreldyosmeilodf a2n,4d-Dweforer oiwnfetarhMetealxaiomrinakieetiednddoetgthfofetehactatwsstloidwgidheeotdregoasrnftmroeetrcoeodaibevsrsiiaenntrggevleetshdtidefofinnhseiegtshohsfeeis1ndt0otd0hgosemsehrgsei..nc/kedNigvl.oeing(sgsTy,am2wb,p4liet,th5o^1mtT)hs..ew;Tdheevreeelceohvpaimndgeeennstt lda2eshwuunro.eh4nacdgpi.gth5sca(isoidh-tna.pin)csfnf.TlFoeanhPloumeIelsaomncuphtmwrhraooomoatwesnditldcioioieosoadsg.cgtnthoswTymendo:aw(igofs1ldeoCdg,tepshshv2ttdrieoaee,toonhlsngid4ogena.si,pnefttefmastI(ud.snn1oetsid3ieeHbnnmdsta6iaresaeoln)trtndfhovdmnyerleaoeeu1dnccgsfc6oaiesiown)scriseevodaeahsxifilr.nnlaeiytdaggdh,Oel,seia2amtnwht,wmhe4imeete-uiedDwirgacdleobhodagottasslodavnilma(eoedti1pgsnhidp3strteeew,toa)hderggaoeehsanotnassoddfsttmdolhrryomngoaeaioslwndynlnmauote(iselendt1posott3etdtenusiocesnoibaiatrmafuipna.inlcntldeeeate.r,crnua1hemddIc7acniet)nofrgfgoansuefesnoiensaisdmdes,, e oTaddfohmg2eIs,iI-4ndr.-eioDscCgtershiaovrtrroiienon2cgni,e4c2io,v,5Of4i-nr,2T5ag0-lTp2mTe0aogrnxVmkdiickgliigon.t/.ygko.ri--gnan.me-d(odaifovo)figdthMbereodesodcerdeytioacvwsloieinmtesygigp:.t2who,tuA4icn-lseDdlusrdavo(diTdgviaseeayddbrelpdtechrue2oeir)dvi.9unin0cgg-eddt2ah,yde5et,asettosuhtrdiyp1n.-e0rbTimoohtdghe.. abnegha((n&cns)l7)etGBtoheoan1dt2eyfrdaaWiallyeSesdiygbmthoeptf:ostourTemrvhtshiev:eeoDdnteohlaygetshssittgohunfadittfyhisceua(rTdnvotaigvbc.ehledan2tgh)ee. inLobsosdyofwweiegihgthot cicnutrhreedseindothges oral administration of 2,4-D or 2.4.5- T for 90 days were free of any symptoms. 1 249506 *036*24MOO 4 f oeswuvffmettenTheitebrudwi*a)r.l,itlU(sfyjuTcfdorrhe-nviezovlegiptevner,edsenawosaplngwhrartadeesswatsfsstpauiofhvrosaaoseeonltlsmdfsieodgixvtiahthestehtoedeosnmtamhswsdteeaiaoahonxglooinlitsbon.aebszosTrewoirhenrmhlocvaugeewseasidolvehp.ofdiirinfnenMbgsddlcoetuitahfnloshfneectdiegn.claseuehfcrlDditwtougoyumtehdneriruoeinesntssghttgcuhwedfhedtooaelhgiodsseweuedslmim.iloniaT(sggofushhrt2aseoee,unt4rrwads-dtilDsoinolbfwygfuttlsashoychrlceewloottaahwhhelwdarireimineneldnyedugquscdluciseoagaiougsennynaastdssl,,. Ta bu 2.--Body W tight and Survival of Dogs Ftd 2,4-Dickloroph*mxyac*tie Acid m d 2,4J-Trickloropktnosyacttic Acid for 90 days Do Sot*- a !_................................... M l .............. ....................... s a ................................... a r -- ............................ t r i e ................................... a _ ............. ; ................... 1C.................................... m u .................................... U t a .................................... a a ................................... a r ,, ................................ M I L .................................. M I L ........... .................... Doan MS./XS. _ ................................... a x ..................................... a t - ........................ a a . ................................... ia _ ................................... U K . ................................... a r . .................................. a x . ................................... u r . ................................... a i l .................................. ............ ta _ ................................... a r . ................................... a a .................................. sat Initial. If. U -D . 1C M IS 1U 9i 1X 0 1L T US ITS ias u 1U 1X 4 1 T TJ 1X 1 us at IS us 1U US aa US 1X J 1C IX n a ti. If. 1X 4 IXft C 1U M 1U 1C 1UB ITS U.T ii. 10J ar T.T 1CA 1ST US u US US US C l - .. a r TS - - 1S T as Sc +ar + 1S +ar --1.4 os -M S +ai -M S -M S + 0.T --a s --C l --I T -M S -M S- + 1S + 1S --OX -M S --X --c * --X --Cft -- J -a s --t T Dwte Dart S S s s s 4ft u m a a a a a 4 Tf U m *ttDaTslliaatrttadataloitsiatthaawlstaadmmsmmamdmamdtettarsliaorlmtaa:taInL)dasasnstaath.astalfplaartae.d.a . aad oostal la a. a . Isbnlliegedhdotingsgatiiftrhfonanetsssdthteien<grgtwhaehaeilh^einrdeceleivgisn^gd2if,f4i,cSu-lTty, itnheswpraollmowinienngt febfofeCctsamwten waeoaAkndeoss,. ^mdcircvrmeieaid^tohhrgcTfafhihn;eeiwrdmmaadaosdulgmsorl.oibinbnsIgeiinnsrtvt,hrteahredterisedot(euTncdaaeoynblf.illmeT2c,hao34leu)-sDn.dttih;fofaoetrrred2nti,oe4tidt^aa5lla-MtTwtoeh<orifmdtledci-noncauoelntiltfehrcelaolmvuienanitantnhecydef 9th0y-dr(oa*iydypgOelrarigondadn,oafWdsrteueindgyahl. tsg:IlnanTtdwh,eohroeefarwtth;aesltihvnreoere,sodigorngiksfiidcthnaanettydciihneadnadnguiemriiannlgs tththheeaatwdsemuigrivnhiitvsteordfatittohhnee.- 15966 5 owfa2s,n4o-Dte,d,thinertewwo aosf athselifgohutridnocgresatsheaitndhieedaratsaandreksuidltneoyf 2w,4e,i5g-hTt.. A similar change dtrheoed(np(5e4/9s2)tshaGidndraioyftsfh,sueasPedgalyuethnoroederledaondlguiezymne:ed.dTWicdwtuieotorhuddseotnhgwuesamrasedadcmneeimdivniojinesngtjsruat2nrt,aiu4otm-enDd,.ow(f2h26il,e4a,n5ind-Td3o4tgh)e4sr8he,odwaeuevtdoeplaosrpieeeadds ooinnf Tail* 3.--Effect of 2,4-D and 2,4J-T oh Hemoglobin, Total Blood, <md Differential Counts DorKo. aDo./m*,. Dty . GHmb..* a_.............. too* U-..... ........ Mon* S I .............. - Mon* 7M............ . Nom- m9. 99 9 so mm0 9 m i1a&M.a0 11 14.71 14J9 1M9.7O9 11.74 1iua1aa9 a n ............... w - a r................ t Ms aH.............................. a ma9 0 0 M9 1iloUU.at u14n.4s UJt 119 11449999* s a ................... at i r ................ m ................... 3> s i .................... a a09 9 am 14M199S44- U.M 1499 it1r1u9at4 tu n BMBCOILo.ntrol DWoB*O ' K%Ot.n LymD%p-lf-afm,-oMtA%i^os-nl .C.o o at lu% , So%da.,' DDuAtft 4M99l- 4.09 491 44.949' 8.09 899 699 1IuM7a3Ss u1T0nJ3OsoB 14400 UJM 14.700 MMn a7aS- S9trB u nu. 47 SHI 34 19 IS 00 00 30 T 0 0 0 10 10 10 4T 9 99t I 9 ,,,, .. ,, .. .,a, .. 899- 8.79 4.47 14409 Ut3, m 89 au 3a9 - t41 a 0 0 4 7 0 .4-D 8n91s uUS3DS 499 11400 8S9M9 14.9700S9 497 uas 8.71 3 .4T 494 1144 LOT 81J999 19.409 10419 197 4909 .7-10 499 an auai Ui Uu1u4J34sMMaa 14 74 aM 70 84 47 77 * - a34399t 14 4 4t 7 a a 4* 3t r1 i4 4 n7T is 19 4 4 4 9 1 41 71 399 3 9 a a7a* m4 us 19 1 04 09 099 4 9I 99 9i 9u 91 9 10 9 9 99 7 41 0 0 9 1 ' 9 9 ,, ## 49 u ,, 3 ,, 49 TS 11 a T*t DoTawblllyitadbowiiaa adMn daa.doanaMalydHdsadttMaaHHoHaltaaionMadgttonlmdhosslsf alaada.Uam.UaadduonMdboaalat laaaa.e at a. . aTdeddaheeBurnfaflr#utiy(|hi|mS&tfi>fwoniiotffddMfiafrleitendimircgcyaoe,rotgiioahnsovsnosnic2intwmor6goape,atifve2l3ce-c,44r(Cea,,T-lnhlD4wasya2bani,sslnsgehiageonnt4nswhod:)ietfe4idTarcm8enahlanduasentchtewoohcodswheacaaascte.nroadjtTgsu,eievhdolisaugetn.hrneayeTsgdliurshnab,ttgrromheetehedauhyecedorogooofforssiefadtefeho,nsaoceoanafoddldfsrtoihenghsgneeenysacrpiclofre,roioscermsaoaecivnemspwicaoviieraeuniy.nrn,eaTgdtohnshnder2eoo,t4rslredmio,vs5utmtaeh-oeTrlees.. DflW 1 249508 15967 1 6 0W 1JM M I hut agianinthtehinsuwmabseurnorfelcaatsetds tion dkoidsnaegye asnecdtiwonass wofasdonuobtetfdulinsisgonmifiecadnocges. CO M M ENT acpttohdrroeodtsdi-hnst-uiaie-onc-ctn-egk-o,Jsobswtiofsgaaemcntsrhusveegteecdrdhahossiagtanpursfadedtscdeihlter,ieosmrwv,wibashsestriiid,niccoghwsuloiehsgmfenleacnasxylriopglniifeeifnctrideariomridlrciateambalnttyeydtiaoootmltnhsoeeesnasnpinsieaonhdc.fgoiepTeu2saah,l4lidinh-seiDarrwdrsei,fhatfaremdeetnmcicaotetyinhinov.eipfesTotsd2eikh,nr4iieentn-dDjteoeoxctfowttateihoandensssopsigbos.i1snsin'm^*amkalilnaIooanydfrr Ta su 4.--Histological Changes in Liver and Kidney of Dog Fed 2,4-D or 2,4J -T for 99 Day Doc Wo. KDr./oK.c. maaJSmanaaukTst.......o.......................................................O......................O..............................O........................f..........O.......................O..........................t.......M.................................O......................O...............................t..*..................................... NHoo1fntaaa awIaIfsfstttt- 4aS444u4aaa410S104sI............t...............................*......................................M...........................................M............................................................................n...............................................................................................................................- Soso Soafa. f1taI1Iaf0ttttt IS Unr DDmsra .. .,,. m . M-DO oncorton 00*00000*111++++4 Mr-o-B-M-NiS '/ - Gotta 000f00000f11tt44-- f01t4ff1tt4fffftttt ,, U>T ,m .0 ..3..r n m 000000*101H44++--- fftt t14- f*1t4-* ff0tt ff1tt44-f9t 1144--' fHt - ft ft tub. Don' ffftfftf91V0tttttt4- * fftt*. 1fct4 fftt ft ffttft trxm+OtC am M i it %J+, *+>,+< ebcyeeeninst,rgaallnimldesittiteoiadnn.htnettOwtmshtta*hpi*efferTdn-neehweslfBseafcgsyeeeo.ecixfudntfisue,atcdohoatscsecn-cc.doauharfsriwenir2oied,gnn4iigga,lv5elheslg-ytenTsvl,o,oeasbtprnhsasr.deeleArvdvsailayoettyahnduxsodsilwuraayogf.emthsreT,teeruihndtsdehiniteeeiehdvaeial,ergdliwehonmfepgefreier;necddritsusnostblrotmoeabtwstaiianolyosygnfb.seiooeen-fvfi:steehttthrbheeeeneer^-' 2d2d,oa,44ig-lsDy3 w.oPriTtaphhltienfa.dsh1mii8ghinintgsoiis:aot4sribt9iauistdediooiraevfnyses,bod.otfThdin2yeh0idaswmnodeigmgiesgl.aa/hsklytusgerwd.vdiioydvtfhieenoad2gtu,h4dtf-ormDaospemapsyparotroihnfededn2uitc,c2eai05ldtl,emodearfegfa.ce1/tuckh0tmgsm.i.unlgdaH.tothiosovrewfeeeeo2evf,fo4eff-r2eD,c,f4tot-houoDerrf :.i <3 7 ddAasWtnrlnoieiafldgssilfttesiehhfo,trtofhnedobumed,iorfrtuf7ts2hihdsoc5,eco4umtdlhgl,ear5tesynud-wsigTpawmihsnya,hiaasnctiltmocshhffdheereoaotwrxhgnremehiesdncwigebsstdaheitiivutoseofeedfmrsadidyecss.utcws2etlhTeotr0ayiemoelbnlmfxoiielnniywigcanisn.ila/nwetklgfthsoaghf,teseli.elsfacoaftnosnwiscnfadeuimisn2tnobeseg,co4tcsod,rhft5afyaoues-nosditTwoghdeienee.esasaiTuan.hlglcsihiyWhmcnuttudhbasim,tllalehstbetehgecdoteshdoibnentacbgashncieinsrdhftotrwereonaodnemtinetacwilnxcyotiihtaarthieha,ndelcm2wgl,tuui4oe1ndm-a1xiDekstisdhc.. o2pddpcleaf.oaeeu4nyrrgct.iitss5hDppo.-echhctohoyeegdlaTtrrsiwoeaant,gllgshcsmuebtibohcrlliuiovh(eocn6noiroev54etddh0i,w.enipwnm5mghiHc7aioogttc,siuhgnhl.a/lreleakoenarbg.cdden1dhi.condere1og,ofi0fCivntn5ao2eaiin)ct,dtra4edlidwl-scDoadblhheseliroedwcc*osohernahedcosiaadrcfcseviaeoea2edidusn,m4eoinjnWe-btiDisncsn,hteitishirooolttveehenrreresrdd2epedi,epct4fahreef,ice5iernfverar-teniceTlrnlnaetagvtniwdignetai2aednlots0ohbfonuelnmfoolsoyptloglymodys.a/lhmpekylcotahgmpoecwo.hruhocaonoyratdcpifttnyoaehy2tynsoIe,n4snsifini-uongDticrhnntlrtwiesehfoiatioexerhr e 2oocsih.crg4gcrn.oaa5Lisnnf-aiiisocrcnagTeonaexrclalwadeymloe(sdirpnTeeorseoasdnebdo.solufetcp2erc4,o4do)d-r.DsruoecDmlaeaeddteaemotdnhinenslwciysrditotauehsrriseisslndiiggignihnntithttfrhaieacnevacdenlhintivrnooelcuenro.ssilincoyHsoniosrsoatrwe,linneiatnvdtfehmtorhec,ieantllihipsvnerteereracas,tredionokmstinidissnnotioeusffydtr2,yda,,ot4oiu-oorDbrnaotfltooulhyrfler SUMMARY apomspprrgaoap.ldTsroduLphxcd-eeeiDtrmyda..makcatuielftdoloeyegrfroi1a2nr0m,ai40tle,5mLom-rtg.rDy.ihoc.phMitegolrohnoreikfaori.pl2aohc,g4eScrn-ouadommcixhcpyhoaaltfnocoirbexeotoidipcdchybaedyndwoodasexenisygo(a2hrpcet,4.erxo,ti5iDdac-uoTacasn)ededdsdwiwano(sen2til,ihgy4nih-stDtshrilg)aeonnsrssigan.enoTgdofheoreagohsfaigmcw1hui0aeltd0ser 2sy.4m.5Ap-tlol Tmdos5gosdrsacuyhrsvaniavgewedseetihnkebfooorrd.ayal wfpeeeeridgiiohndtg, oooffrg92a0,n5dw,aoyeisrg.h1Tt0sh,meosger. bdploeosroedksicldooigudrnantm.otopfro2d,4u-cDe oarny dsgisntwiuuematddThly,lseoh.,awrpTnneeideoenrccxgoarei,olf,cnltbittithfacuyoegtcuetftohrohoaeu2dfnr,orlg4eygde-msoDswgpraisnheascotroetacthnchyveelteiyeinvbsdgliuoinwtcs2gtcala0easgrleemeopmvblegiesaud.vetcereeponvldescewraedd,aokoisasinflneoasdctcghlcorirsnoafeomime2cma0poeloafmfnmdtighi2eyf.ed,fo4iptca,boe5unynr-litTimykab'i.alldeiloAnseige.ddrcitanhemgdremwuforriiifnnonagm2gl,4aftt-nhahDldeel to pDatehaotlfoegdiucrailncgh-atnhgeerseipneathteedliavdemr,ikniidstnreayti,oonroofth2e,4r-oDrgoanr s2,e4x,5am-Tinweda.s not related P r im itd t a d P a U U k td m I k e U m M S t a U t * f A m e r ic a DOWf 249510 r\f\ O pS-' - 5(D W 7 5 0 5 2 4 C . R . I Name : INDEX HEADINGS T2,30-40-3 Page 2 Ku rc r ___________ ____ Common Name: J`- P l r- -I D O , ) DISTRIBUTION The Dow Chemical Company, Midland Director of Research - R. H. Boundy Central Research Index Legal Department - H. H. McIntyre E. C. Britton Research Laboratory - R. P. Perkins Technical Service and Development - A- Hart Spectroscopy Laboratory - N. Wright Agricultural Chemical Research - 0. H. Hammer, T. A. Hymas, Physical Research Laboratory - G. D. Jones G. E. Lynn flhgwilcci'lQ Dcpnr^im rmhi-'5B;fi5; M '';Athay Agricultural Chemical Development - H. E. Gray, K. Barrons, L. L. Coulter Midland Division Medical Department - Dr. H. H. Gay Safety Department - W. L. Tisdale East Main Laboratory - E. N. Luce West Main Laboratory - L. M. Greene Special Services Laboratory - V. A. Stenger Prescotts Division - L. C. White Texas Division Central Research Index Industrial Health and Medicine - Dr. D. J. Kilian Agricultural Chemical Research Laboratory - R. W. Colby Western Division Central Research Index Safety Department - D. Elshere, Pittsburg Agricultural Research Laboratory - J. F. Kagy, Seal Beach Jd 1219-li PrtntdInU.3.A. HI1-58 15971 'I FIRST LITERATURE REFERENCE OTHERS (NAMC. S'JCH AS ORGANIC RROO. O CV C LO R., AROMATICS, T .S .4 Q .; GIVE LOCATION) *> vr1 February 27, 1959 c c : V. K. Rowe (2) T 2 .30-40-3^ T 2 .30-40-20 Correspondence '.cv*. < .- l; ; ? . :'V Joseph V. Blander, M.D. 1934 Spruce Street Philadelphia 3, Pennsylvania O Q Dear Dr. dander: Subject t KURON As per our telephone conversation of February 27, 1959, I have sent you under separate cover samples of the ingredients of Kuron. They are designated as Dowco 134, Dowco 135, Dowco 136 , and Dowco 13 7 . I think it would be very Important when you recheck the man who showed some response to Kuron to Include these materials in the check. I would suggest rechecking as followst cn Ctc0oOn Kuron at 0.1# in water Dowco 134 at 0.1# in sesame oil Dowoo 135 at 0*fc# in ^ , Dowoo 136 at 0.01# in seesaw oil Dowoo 137 at 0.-&5# in seo^mis ell c c l Such a check should tell us which, if any, of these materials is responsible. If no response is obtained, it would seem desirable to inorease the concentration of each by a factor of 10 and retest. If additional costs are involved in these additional checks, they can be Justified. I trust 2 have made myself clear. If you have any questions, let me know. Sincerely yours, V. K. Rowe Biochemical Research Laboratory 12-634 Building :'Jr * VKR/vmv 15970 P.3. As I told you, Kuron is used at a concentration of 3 to 4 parts per million or 0.0003 to 0.0004# so our margins are large. Naturally,, we want your conclusions to recognise this usage. D O W 531498 D r . J o s s R . ' - i V. K c a u d e r 1S 34 S ? a u c e S t r e e t PHILADELPHIA 3 a r> )r ioou Juno 22, I96I Dr. V. K. Hava Biochemical Rasearch Laboratory Bov Chemical Company Midland, Michigan Dear Dr. Hava: ... I herewith report final result of repeated insult patch test with 1 per cent aqueous solution of Kurasal SL. The test was performed on fifty male subjects. A cloth 1 x 3/4 inch attached to an Elaatoplast was saturated with the ICurosal solution ar.d immediately placed on the skin. This was repeated three times weekly for twelve consecutive times. Two weeks later a challenging application was made. As shown in Table I there was no cutaneous reaction after removal of each patch. There was therefore, no evidence of primary irritant, fatigueing or allergenic action. J VIC:j s Yours very sincerely, Joseph V. Klauder, M. D.. \ 'u w 531499 . ^ -2- I \ b 1 15974 co 5vr U OV)' CD vH 'S .<0 *3 o CT' \J ^* :> I 9! .o >* 5 ? 5 I 3:->, 5 a -V 8 so > *) ~k v_> *1 I I. Dbw b6b427 ' MN07'J280 i ! i i v> i 15975 MjCSLATD oUiy 20, 19o2 .-u.* > 7 , ' ." .7 .7 m . X _ _ O .i Dow Chemical of Canaca Sarnia, Catarlo, Canada D W 533170 Soar fed: As par oar discussion by telephone on the 17th, I have looked up the toxicological data v.a have r. hurosal SL and Kuroeai G-. Without gains into a lot of detail I shall atter.pt to summaiza it for you in the following pa agraphs. AUAGSAL L - FC-FAlULATIOh: Z-.-1845 Acute Oral Toxicity - Rato then the formulation as a 2C',j aqueous solution was fed in single doses to rats by intubation, doses of 1 g./kg. were survived and closes of 2 g./kg. were lethal. Apparently then, the LD^q for this formulation lies somewhere between 1 and 2 g./kg. We have not attempted to define it more accurately. affects Tj-oon the Eve - Rabbit Vlhen the undiluted formulation was introduced directly into the conjunctival sac of the rabbit, the material produced severe conjunctivitis and corneal injury ouch that impairment of vision might result if such contact were experienced. When a freshly contaminated eye was promptly washed with water, the injury was considerably reduced but still rather serious. When the formu lation was diluted to l(,j with water, it produced only a very slight transient conjunctivitis. Sain Contact - Hobbit When the undiluted formulation wa: `ined 00 the akin of a rabbit, it produced significant hyporamxa, edema and necrosis and there v:as evidence that absorption through the skin occurred, since the animal treated in this manner died. When the formu lation was diluted to i-,;' in water, repeated and even concinuoua expoaura over a two week period, produced only very slight edema end exfoliation without evidence chat toxic amounts were* absorbed. Skin Ab ;ornt ion Rabbit In an effort to assess the significance of skin absorption, one cuff technique advocated by the U.S. Pood and Drug Administration 15976 ( **T Uiffon July 20, 1962 was empioyed. Using a 50 aqueous solution, a 24-hour exposure, and a dosage level or 1 g m /--?>- of t h e 1 1 - 1 3 4 5 , none of the animala died tut there was evadente of irritation and some V.' o ' *1 G I C w j c: * ; - ,, a . ..J * ..... ... . rV..\fc.C.: or, i-:u::.;nrno ICnrosai SL wan tested foe* vs on 0 human subjects by Dr. J. V. nluuder, M.Q., Consulting bernusclogsst of Philadelphia, Pennsylvania, lie employed the repeated insult technique, 12 applications being node over a three use:: period plus a challenge application two weeks later. Dr. IQ.audor selected a 10 aqueous solution as an appropriate test preparation since it was many tiroes the concentration which, would ultimately appear in any treated lake or water reservoir, lie observed no evidence of primary irritation, fatiguing or allergenic action. A copy of Dr. Xluuder's report and a protocol of his studies is attached. Xu PIPSAD 0 - POEiiULATICk: l-io47 Skin Absorption - Rabbit The cry granules of ICurosal G, 2.0 g./;cg., were wet with water and bandaged onto rabbit's bellies using the cuff technique. A very slight hyperemia, edema ana necrosis occurred but otherwise there were r.o untoward physiological responses observed. In talking with C-. 2. Lynn about the ICurosal problem this morning, I learned that he had sene to Jin Johnson a copy of our report of a 90-day dietary feeding study on rats. That, together with this indorsation, constitutes the data wo have at this time on these materials. I trust it will servo your purposes. , Sincerely yours. k/cVc V. 2. Rowe Li cchemical Research Laboratory 1701 building --hene :ci 0-2370 V-CR/Jd L. L. .Coulter 1597*7 BC T 2 . 2 - 1 3 9 - evi Biochemical Research Laboratory The Dow Chemical Company SKIN IRRITATION AND ACNEGENIC PROPERTIES OP VEON BRUSH KILLER, VEON 2,4,5-T, TORDON 101 AND WEEDAR 2,4,5-T AMINE Pile Charge Ref. o o to -fr eo Vai Ul T2.2-139-2 1263 (See below) Weedar from Amchem G. E. Lynn C. P. O'Hare K. J. Olson DISTRIBUTION The Dow Chemical Co.. Midland R. H. Boundy CRI G. E. Lynn G. D. Jones W. R. Mullison K. C. Barrons. (2) M . G. Wlltse \ j. H. Gowell Midland Division H. L. Gordon, MD A. W. Wilson Pltman-Moore R. D. Moss Texas Division D. J. Kilian, MD CRI R. V. Johnston Western Division CRI D. Elshere J. P. Kagy PROBLEM It is understood that a customer mixed 1.5 gallons of Tordon 101 Mixture with 2 gallons of Weedar 2,4,5-T Amine (Amchem product) in 100 gallons of water and used it for spraying brush. The customer reports that some of his men developed a skin rash as a result. He claims further that hi3 men used Weedar 2,4,5-T Amine alone with no problem. The specific nature of the rash was not revealed. Whether or not th dermatitis was diagnosed by a competent phy sician is not known. It was requested that these materials be subjected to the rabbit ear test designed to detect acnegenic properties and to the regular testing program used to evaluate primary skin irritating properties. In view of the likelihood that some other products might be used with Tordon 101 it was requested that the following testing pro gram be initiated. 1. Untreated control. 2. Tordon 101 Mixture, lot 590685- RESTRICTED: for use within Th Dow Chemical Company only. 1597-8 T G T E 6 A/vOO Biochemical Research Laboratory T2.2-139-2 Page 2 3 . Tordon 101 Mixture plus Weedar 2,4,5-T Amine (1.5:2). 4. Tordon 101 Mixture plus Veon 2,4,5-T Amine (1.5:2). 5. Tordon 101 Mixture plus Veon Brush Killer (1.5:2). 6. Weedar 2,4,5-T Amine. 7- Veon 2, 4,5-T Amine, lot 870665. 8. Veon 2,4,5-T Brush Killer (lot 8802558880244). TEST PROCEDURE All materials and mixtures were applied to the rabbit ear and to the intact and abraded rabbit belly on a repeated dally basis. The materials were placed on the belly areas under a cotton pad and bandaged to assure intimate contact. Three applications were made to the abraded skin. Ten applications were made tothe intact belly and the ear unless prior exposure produced a moderate to severe skin burn. Folliculitis, indicative of acnegenic pro perties, was evaluated daily in the case of the ears (see Table 1). 15978 Table 1 - RABBET EAR TEST FOR ACNE (UNDILUTED MATERIALS) Materials No. Of Days Appl. Exposed Response-Results Control Tordon 101 Tordon 101 + Weedar 2,4,5-T Amine Tordon 101 + Veon 2,4,5-T Amine Tordon 101 + Veon Brush Killer Weedar 2,4,5-T Amine Veon 2,4,5-T Amine Veon Brush Killer 0 10 10 10 3 10 10 10 0 No response. 16 No folliculitis. 16 Slight to moderate folliculitis. 16 No folliculitis. 15 No folliculitis. 16 Moderate folliculitis. 16 Slight folliculitis. 16 No folliculitis. 15980 4 2 6 U & 6 M oa S31753 O Biochemical Research Laboratory T2.2-139-2 Page 4 The test for chloracne was repeated Increasing the number of applications to the ear to 17-19 and the days of observation or exposure to 3 5 * On this study the four products only (not the mixtures) were investigated, undiluted and as 10# solutions in chloroform. A volume of 0.1 cc was applied per dose to the inner ear in all cases. The data are summarized in Table 2. 15981 Table 2 M aterials Veen Brush K i l l e r Veon Brush K i l l e r Applied As No. Of Days Appl. Exposed Undiluted 10# in chloroform 19 19 35 35 Response-Remarks No response. No response. Veon 2 ,4 ,5 -T Veon 2 ,4 ,5 -T Undiluted 19 35 S lig h t f o l l i c u l i t i s . 10# in chloroform 19 35 No response. Tordop 101 Tordon 101 Undiluted 17 24 No response. 10# in chloroform 18 39 No response. Weedar 2 ,4 ,5 - T Amine Undiluted 18 34 Moderate f p l l i c u l i t i s . Weedar 2 ,4 ,5 - T Amine 10# in chloroform 19 34 Very s lig h t f o l l i c u l i t i s . OK CT- vt freiTee m o a D O W 831795 Biochemical Research Laboratory T2.2-139-2 Page 6 The data recorded in Table 3 summarizes the primary irritating properties of the materials as indicated by the rabbit belly. It will also be noted that the skin response regards folliculitis was also observed. In general it is felt that the rabbit ear is more indicative of acnegenic potential than the belly. In these cases the ear and belly data are consistent with the exception of Tordon 101. All ear studies are negative whereas the belly showed a slight positive reaction. T^i3 can be inter preted as meaning that Tordon 101 possesses a very slight potential for producing chloracne. The data indicate that Weedar 2,4,5-T Amine is appreciably more potent than Tordon 101. It is incon ceivable that the customer referred to above experienced chloracne with the Weedar-Tordon mixture but not with Weedar alone. None of the materials or combinations were tested as use-dilutions (about 3*5# in water). It is possible under conditions of spray ing brush that a skin rash might result from prolonged, excessive contact, even with such dilute solutions of any of the materials. A rash might be of a primary nature or chloracne. A competent dermatologist should be employed to diagnose the nature of the rash. Veon 2,4,5-T Amine appears also capable of producing slight chlor acne although under the conditions of the test the Tordon 101 Veon mixture did not. This is probably due to a matter of diluting Veon. Further applications would probably have proved positive.* Veon Brush Killer and the Tordon 101 - Veon Brush Killer mixture were negative under the conditions of the chloracne test. The following summary of primary skin irritating data indicates that all of the materials and mixtures tested are capable of producing skin redness, swelling and even a burn in the undiluted form under repeated, prolonged conditions of exposure. As usedilutions they are not as likely to produce a rash, but if extensively misused and if clothing were to become contaminated and not changed from day to day, a rash could well result. Good care and cleanliness should be practiced at all times while handling these materials, either undiluted or as sprays. 1596 Table 3 - PRIMARY SKIN CONTACT DATA SUMMARY M aterials Control Tordon 101 Rabbit N( Suemxb)er Condition Of Skin No. Of Appi. In ta c t m 364 In t a c t (M) 0 3 Tordon 101 Tordon 101 + Weedar 2 ,4 ,5 - T Amine Tordon 101 + Weedar 2 ,4 ,5 - T Amine Tordon 101 + Veon 2 ,4 ,5 - T Amine Tordon 101 + Veon 2 ,4 ,5 -T Amine Tordon ,101 + Veon Brush K i l l e r 364 (M) r .i 3( M63) 374 (P) 374 (F) 472 (P) Tordon 101 + 472 Veon Brush K i l l e r (P) Abraded i Intact Abraded Intact Abraded Intact Abraded 3 3 3 3 3 3 3 4 15984 continued on next page (RABBIT BELLY) Response-Remarks No irritation observed. i No irritation followed first application, moderate redness, slight burn followed second and moderate burn'followed third. Skin healed with moderate scab scar and redness in 16 days. No folliculitis. Essentially the same as above. Essentially the same as above. Very sllgh to slight folliculitis. Essentially the same as above, with extensive scar in 16 days. Slight redness and edema followed first application. Extensive burn followed third. No folliculitis. Essentially the same as above with slight scar in 16 days. No folliculitis. Moderate to extensive redness with moderate swelling and burn followed second application. Skin healed with moderate scar in 15 days. No folliculitis. Moderate redness and burn followed first application Burn became extensive. Moderate scar in 15 days. No folliculitis. O ffT p n J Table 3 - continued Materials Rabbit Number Condition No. i (Sex) Of Skin Appi Weedar 2,4,5-T 373 Intact Amine (P) 3 Weedar 2,4,5-T Amine Veon 2,4,5-T `Amine Abraded Intact Veon 2,4,5-T Amine Veon 2,4,3-T Brush Killer i 373 Abraded (F) 359 Intact (P) Veon 2,4,5-T Brush Killer 3(P59) Abraded 3 3 3 3 3 Response-Remarks Slight redness followed first application. Extensive with moderate swelling and burn followed third. E x tensive scar in 16 days. Moderate to severe follicu litis. Essentially the same as above. Moderate to severe folliculitis. Moderate to extensive redness; slight to moderate swelling followed first and second applications; extensive burn followed third. Skin healed with moderate scar in 16 days. Slight folliculitis. Essentially the same as above. No folliculitis. Slight redness followed first application. Extensive redness and moderate burn followed second and third; skin healed with slight scar in 21 days. No folliculitis. Slight redness followed first application. Extensive redness and moderate burn followed second and third; skin healed with slight scar in 21 days. No folliculitis. 6 I 6 /a o a  DOW882210 MN00252? f >1 iiO^ l ;<J HQ Health Hazards Associated with Handl ing and Use of Herb icides by V. K. Rowe iechemicol loseorch O ip o rlu tn i The Dew C h in U p l Company Midland, Michigan Krpriiiicd |ruw Febtuury. 1**12( ! j j i . m u : a i . * i miu* i>| 1596? ' ti f Health H azards A ssociated with 1 ~\ Handling and Use o Dcy 882211 THE purpose of this paper is to outline the health hazards asso ciated with the handling and use of some of the herbicides employed widely today. Before discussing specific ma terials, the terms "toxicity" and "toxic hazard" should be defined. Those terms are nut synonomous although they are sometimes thought to be; toxicity is a property of matter; it may be defined as the property of causing injury to the living organism by other than mechanical means. lTikoexliichohoadzatrhdat may be defined a substance will as the cause toxic injury. Warning properties such as foul odors or tastes, lachrymation, or irritation, which become apparent and highly disagreeable from harm less exposure, tend to prevent the likelihood of serious exposure and thereby reduce the hazard. Similarly, the absence of such properties tends to increase the hazards. Physical properties such as vapor pressure, solubility, dustiness, etc., may either increase or decrease the hazard of a material depending upon how it is handled and used. It follows that a material may be highly toxic and yet may not be particularly hazar dous; and conversely, a material may he relatively low in toxicity and yet be quite hazardous. During the last 10 years, and to some extent during the preceding 10 years, more and more attention has been paid to the effects of her bicides upon human subjects, live stock, and wildlife. The development ingested and in normal use, the like of new and better herbicides and lihood of ingesting dangerous quan new uses for old ones has led to a tities is remote The material is not tremendous increase in their use by particularly irritating to the skin and an increasing number of people and is not absorbed through the skin in to their use over prolonged periods significant, amounts; hence, the haz of time by custom operators. The ards from topical contact arc not likelihood of human exposure to these serious. Information with regard to materials, has been increased many its efface upon the eyes is lacking. fold by these new developments. If hthaensdeledneswafeerl,y, mspaetecrifiiaclsdiraercetiontos tober their use and specific precautions wagoaridnss,t mspiesucisfeicmhuastzabredsissmueuds.t Inheothdeer fined and information given on how to avoid hazardous exposure. In order to do this intelligently, facts must be known about the chemical, physical, and toxicological properties of the material, about the form and manner in which it is to be handled and applied, and about the likelihood and magnitude of exposure. Industry has recognized and accepted this respon sibility. To be specific, what health hazards arc presented by the various commonly used herbicides? and, how Precautions for safe handling should be directed primarily toward the elimination of the possibility of fire and, secondarily, toward the avoidance contact. of unnecessary personal Although cases of livestock poisoning due to chlorate have been reported, most experience lias indi cated that when used as recommen ded, it docs not present a hazard to livestock grazing in treated areas (I). Precautions should be taken to spread the'solid evenly so as not to leave piles of it available and to avoid leaving containers of the material where stock can get it. Salt-hungry stock are most likely to consume toxic amounts of this material (2). should they be handled in order tu insure safety? Borax VAILABLE information indi T ACtaatletoiothncHwaisonEisntgaphsnSrtapiottyrhuchdieeotnedienrcusbuitmpaioscmaeraildiodCenufhrahesatisasletzoeoldatddrrhiadluaitwtmreweaiotishtfcshhohlaccliozrihaeardlta.roerdtrydeV. egeTnestimdooh,tnaelsbpl.murcaaetanarsteNteetehnshrobteieaetrslhlslbiiipgaekiiecntsveciieldiffidtaihaehclioearnolnoheydtucrasenhtoesodesfsxoalaoiiilrincltfnyhgg.isbfehtospeatirrrinzaeoiagxlcnareadnsuasitts.s docs chlorate is easily ignited. Sodium Experience has indicated that chlorate is not particularly toxic if the ordinary use of the material does 15S88 Herbicides not present a hazard to livestock or wildlife. The combination of sodium chlorate and borax (1 part chlorate and 9 parts borax) essentially elim inates the fire hazard from sodium chlorate. Tlic health hazards of the combination arc not believed to be of significance. Special precautions in handling arc not believed to he necessary, since experience has indicated that the material does not present a sig nificant hazard to stock and wildlife. Arsenicnla THESE materials, (Sodium Arsenite and Arsenic Trioxidc) present serious hazards of handling and use probably greater than those of any oilier herbicide. They arc highly toxic.and the consequence of accidental ingestion of even relatively small amounts is very likely -to be death. When, handling or applying these materials, particular care must be taken to prevent ingestion, inhala tion of dust or spray, and skin con tact. Particular care must be exer cised in the disposal of sludge or residues from spraying and of con taminated containers. The hazard to livestock and wildlife from eating sprayed vege tation or from drinking water con taminated by these materials is ser ious. Calcium Cyanamid HEALTH hazards associated with the use of calcium cyanamid arc those resulting from conttct with die akin and eyes and from inhala tion of dust. The hazard from possi ble ingestion is of little significance. Precautions for safe handling should include measures to prevent -contact with the skin. W hen hand ling dusty material, coveralls which fit tightly at the neck, cuffs, and ankles will he Iiclpful in preventing skin contact, as will wearing a hat. Exposed surfaces of the skin may be protected by covering with a bland oil or appropriate protective cream. The skin sliould he washed thor oughly at the end of each day. Con taminated clothing should be washed before re-use. Care must be exercised to pre vent cyanamid from getting into the eyes. If this sliould occur, the eyes should be flushed immediately with ail abundance of dean water and medical attention obtained. The breathing of cyanamid dust sliould be avoided. A respirator should be worn whenever the breath ing of dust cannot be avoided by other means. This is particularly important when exposures are repeated or pro longed. by V. K. Row* l l tTchk*r aDMl os witdl laCInuhde. mmMikciacIilhigOCaoenpmapratmnyant P a P r n a n u l a t M a rtS a a in ra WaaS O a a lro l I X a la m n , N o Y arS C it r . Jmaia. ary 4, last. dcyuacnedamsWiidgnhiieftincuanstehtldey,. gthraenuhlaazrar-dforims roef Herbicidal Oils NUMEROUS oils have been used as herbicides, alone and in combinations with other mater ials. Huwever, a. discussion of the individual oils is beyond the scope of this paper. Toxicological information re garding the oils is very meagre. Judg ing from past experience and what ia known of the toxicity of petroleum fractions, certain generalizations arc justified. It is likely that the most significant hazard presented by the oils would be that of dermatitis caused by prolonged or repeated skin contact. Contact with the eyes may be quite painful, but serious eye injury is probably not likely. The hazard from ingestion is not usually serious unless such materials are swal lowed in substantial quantity. The hazard from inhaling vapors or mists of the oils when used as herbicides is not believed to be serious, mainly because the likelihood of inhaling ap preciable amounts in normal use is very small, .flie hazard from fire should not be overlooked. Precautions for safe handling should be directed toward the avoid ance of prolonged and repeated skin contact. Clothing, particularly shoes, wet with oils should be removed and cleaned before re-use. Heavy mists of oil alone or in combination with ouretnhpdeeearrtteocdxelyirctaaoninrts (csoohrno-udplirdtoiolnononst,gberedesbpprieerraaitothodesrdy-, protection may be necessary to insure safety. Ammonium Sulfamate USE of ammonium sulfamate as an herbicide does nut present significant health hazards. This con clusion ia based on toxicological stud ies conducted by Ambrose (3) and is bome out by extensive use over ^n appreciable period of time with out reported injury to either humans or livestock. No special handling precau- 1 5 9 8 8 DOW 882212 tions are necessary. The material presents no fire hazard. Pentachlorophenol In instances where contact cannot be avoided, the necessary protective clothing should be worn--such as goggles, rubber boots, and rubber AZARDS attending the use of gloves. pentachlorophenol are those of H absorption of toxic amounts of material through the skin, skin irrita' Ttion, eye irritation, and ingestion (4, 5, 6). There is no fire hazard. The dusts of the free phenol and of . the sodium salt and oil or water sprays of either are quite irritating to the nose and eyes, sufficiently so that toxic amounts are not likely to be inhaled. Pentachlorophenol may be absorbed through the skin in toxic amounts from concentrated prepara' tions if contact is extensive and pro* longed. The irritating action on the skin will vary considerably with the solvent. In general, strong solutions (10% or more) may cause skin irri tation on single prolonged exposure, but contacts of short duration are .not likely to irritate. Fine dust or so lutions as dilute as 1% may irritate upon prolonged and repeated ex posure; if exposures are continued over a considerable period of time, an "acne-like" dermatitis may de' velop. Special tests conducted on human subjects have suggested that the 6odium salt, but not the free phenol, possesses a slight tendency to cause hypersensitivity. These results are interpreted to mean that a very few persons may show increased sus ceptibility after once having a rather severe rash; in practice, this has not been of importance. the Dinitrophenols HE hazards attending the hand ling and use of the dinitrophen- ols (Dinitrocresols and Dinitro-o- secondary butylphenol) as herbicides are predominantly related to their acute toxicity (8), to the ability of the skin to absorb them, and to their rapid absorption following inhalation of dust preparations. The dinitro- phenols generally do not present a hazard of skin irritation or eye in jury; however eye irritation may re sult from contact with certain prep arations. Rarely a person exhibits hypersensitivity to these compounds; if so, that person has no alternative but to avoid them carefully. Some liquid preparations are flammable because of the solvents employed; the dinitrophenols, except for dry sodium cresolate, do not present a Are hazard. In handling dinitrophenol con centrates, either solutions or dusts, precautions should be taken to avoid skin contact and inhalation. Protec tive clothing such as coveralls, hat, rubber boots,, rubber gloves, and a dust respirator may be required -- depending upon conditions. If con tact with concentrates should occur, contaminated clothing should be re moved promptly and the exposed skin thoroughly cleansed with soap and Although pentachlorophenol is water. rather toxic when swallowed, its use In applying sprays, prolonged as an herbicide does not ordinarily bieathing of mist should be avoided. offer opportunity for sufficient in W hen clothing becomes obviously wet take to be dangerous. with dilute sprays, it should be re Its safety in regard to live stock feeding upon freshly sprayed forage has been indicated by Grigsby and Farwell (7). The hazards associated with the handling and use of pentachlorophenol can be avoided by taking pre cautions to prevent contact with the skin and eyes. If such contact does occur, the material should be removed moved- within a short time and the skin cleansed. It is always advisable to bathe each day after applying spray. It should be remembered that the staining of the skin and clothing by dinitrophenol compounds gives no indication of the quantity absorbed or of the actual hazard involved, but merely shows that there has been tome contact with the material. promptly by washing. Contaminated The improper disposal of clothing or shoes should not be worn. sludge or residues left after spraying cbaendipsrpeosseendt oaf hsaozathrda.t tThheeys-ewislhl onio.dt toawbosreilglsratrevranceazooaiiRlmmtnaegbsmcs.loieledinnvuttdeeaosesmtdoaiucnnpkaaiomrteen(a1lswnf)o.oalatitnaegdrheasszutoarpredptaholtieeuedyss 2,4-D and Others THREE other materials, 2,4-Dichlorophenoxyacetic acid, its salts and esters (2,4-D); 2,4,5-Trichlorophenoxyacetic acid, its salts and esters (2,4,5-T); and, 4-Chloroo-toloxyacctic acid, its salts and es ters (M CP), can be considered together because their toxicological properties are very similar and be cause they are used in essentially the same manner (6,9,10, and 11). These materials present haz oaDrfudssctasoufasniendygestairnpojpnurgreycsioaalbnuldteiosniknsinjaurrieryrcitataoptaiotbhnlee. eyes. Dusts in high concentrations * mreaspyiractaoursye tirrarcitta. tioRnepoeaftetdheorupppreor longed contact to concentrated form wulhaitlieonscomntaayctrewsuiltth indisluktien isrorliutatitoionns,, such as are used for spraying, could possibly cause irritation of the skin. Hceopwt,evpeerr,hathpiss, iisn htihgehlyunuunsuliaklelyly seuxs lceedp,tibthleesepemrsaotne.riaAlss aorredinnoatrillyikehlayndto coarussekinsksinensiirtriiztaattiioonn, (6ey).e Tirhrietaytioanre, anloipuokpste.rlayebcistaToobrhblbeeeedexintithnehrgnaoetlue,stdgai,nohdnatrhieneotnsfhkoeitnahhmataorozmuaanfrnudtysl amounts is not likely. In themselves, 2,4-D and 2,4,5T do not constitute a hazard to live OssatonmcekthiegsrbbaazesliiinsegvoefodlnatbootrrbeaeatotetrrdyuesaturoedfaiseMs,(C7thP)e.. However, it has been suggested that spraying with 2,4-D and 2,4,5-T may render certain plants toxic or possibly make some toxic plants more palatable or attractive. This subject is present ly undergoing considerable study; its practical significance has not been great, but cannot be evaluated fully until more data are available. JL -S S 9 0 D O W 882213 Precautions for safe handling the National Cancer Institute have disappears a few hours after .discharge should include measures necessary to failed to substantiate' this hypothesis over soil and will not keep children prevent dust or concentrated prepara ( 12). or animals from crawling under gas tions from getting into the eyes and to avoid prolonged and repeated skin Methyl Bromide retaining covers. Care should be taken to keep children or animals O W 882214 contact with concentrates. If con tamination of the eyes should occur, Tthey should be flushed promptly with clean flowing water for at least I? minutes and then medical attention should be obtained. Sodium Trichloroacetate QODIUM TCA in concentrated O form, presents hazards of skin itrorriytatiirorinta, tieoyne. ir.Trihtaetimona,tearinadl prreesspeinrats no hazards from ingestion or from absorption through the skin (6). Con tact with the dust or spray solution, particularly on the face, results in a pronounced burning sensation but serious injury is not likely unless ex posures are severe and prolonged. In halation of dust may be painful to the nose and upper respiratory pas sages, but is not likely to cause serious effects. Precautions in handling and use should be directed toward avoid ing contact with the skin and eyes. Protective clothing such as coveralls with tight fitting neck and cuffs and a hat are effective protection. Con* _laminated clothing should be removed and washed before re*usc. If skin contact occurs, promptly remove the material by washing with water. If the eyes should become contaminated, they should be flushed with clean water for at least 15 minutes and medical attention obtained. No significant hazard to live stock exists front their eating or con tacting sprayed foliage. (7). IPC Materials O appreciable hazards appear N to be involved in the use of Isopropyl N.-Phenyl Carbamate C.) and Isopropyl N-(3-Chloro phenyl)-carbamate (chloro I. P. C.) as herbicides. They arc low in toxic ity by ingestion and by inhalation, (12) and are not significantly irritat ing to the eyes or skin. Although it has been suggested that I. P. C. may be carcinogenic, studies conducted at (I. 'fhsappbvltwudyrrhceoeaapeaoeuorlipaottemasisotirtoondoleothtxoirHwadnno;iwstssiciaspSEinhtnsneI,tnheyierehhogabrn.odredseafoiuctdsspoohlteiffsektdoahnetdrmereaiiitroedahmencsamrilrhimodeetoela.eceieteuscnmrlgohdtasstthnbfhetpltpwmcyyoigieoloosohealdhaotscinistanrisyeabfomecsenotz.roenhf(daodnemaoulr1cfcuerifimme3tonedacrflmneotiudog)eisoihndct,wgsrafryhoe.taattyehaplvaohatntirhenilsreesTtoaboseldrcctezonrylhhhohioofalcsoaaenirohmdnieqznozmacirgvuaagntiefieeaedrrooinhtnikdddddnoycefrillingIsapcnipalbtlaittorohghhatwhtiflrrrcefenmioaeaotaiisieaadttegtcsmcreiailrystgoeoanslitr,idyihcnncieadntfsaoccoetcaterThkgleuneoocrfoaoidssrhprommnenite,uutnahenxadehlmtcourcijtcndhneutheaillreredenooigprcnepnnyjtf,ptemdoaptiuhds.brrstorteirheaitelofnstyhdbihpctadrlmsgeleeoaaupaRtirltvuetmnrpsipihrietktweartmnelgltiaipieeolc-fon.itrealsutolbunegyslptadauwerlmes.ltieaiEies.rdelprkotdrloiin3vedouirnalcrCvn0cyeekurllga.igtivnromnrilneloieeymntomgeiorsonmltsloeniuafrhtondauefclmovcuputttpaodshhueotmlriomiiesdoylenonigsndons.rlf cf inhalation, methyl bromide is now It can be noted from the pre marketed to a large extent for agri ceding discussions of the various cultural purposes with chloropicrin herbicides used widely today that in: added. Chloropicrin is a very strong formation of a more specific nature is lachrymator and a small percent of it available upon the newer products in methyl bromide serves as a warn than is available, even now, on some ing agent, thus markedly reducing the of the older products. The reason possibility that a person will unknow for this is that information regard ingly expose himself to hazardous ing the health hazards of the older amounts of the vapors. herbicides has been derived largely The use of methyl bromide as from experience, some of which has an herbicide involves mostly outdoor been sad. Information regarding the applications. Under such conditions the likelihood of the operator expos ing himself to hazardous concentra newer products has been and is being derived largely from studies on labor atory animals together with obser tions of gas is remote, providing he vations made during the field testing stays on the windward side of the of such products. gas. This practice should also be fol lowed in removing tarpaulins and other equipment from fumigated beds. W hen methyl bromide is used indoors, the hazards are increased markedly. If good ventilation is lack ing, the precautions necessary to in sure safety will approach those re quired for space fumigation. P. In case of spills in confined spaces, persona present should vacate immediately and should not reenter until aeration has been accomplished. If it is necessary to enter a significant- ' ly contaminated area, a gas mask should be wom. It should be noted that the lachrymatory effect of chloropicrin The practice in industry to day is to study the toxicological prop erties of new products before market ing, yes, even before samples are sent out, so that hazards can be de fined and so that precautions neces sary to insure safe handling can be given. Inform ative precautionary labeling such as appears on essentially every agricultural product and other chemicals marketed today is an ex ample of this practice. It takes di rectly to the consumer the following information:" A. Name of product. B. Signal word designating the tic- grec of hazard: Danger! W arn C. iAnfgf'iromratCivaeutisotna!tements of the particular hazards of that prod uct in the order of their im portance. D. Precautionary measures cover ing actions to be taken or avoided. E. Instructions as to what to do in case of contact or exposure. If every consumer would read the labels on the products he buys today and would follow the directions given thereon, it is exceedingly doubtful that a single case of ill effects would result from the handling and use of herbicides or other agricultural chem- icals.skVk- (1) (2) JSaPteW(lor1i.oeiu.e9dcareai4EnnuGdn4a.m.)lH..VHCeRCreoa.bhVntnilecMcootrrielrido.on.aeloat:!errHey4A.Pa8Sgwo,oJMeiodasnuiioeputirdnagmninii.cnanilgnPPCe2oialh3n(as1lntAou-AtCr2sreaes3martossteS.' (3) (4) (T) (6) (7) (8) JTcocMTeMVtAlGmATSStCCtHSpASU3pp(aaauoiho1fg.teouhtoooaohnrccnia.cn.uriuaculu9.rmldexxtxcleechuiohipSpt-dfarislmtnm4ihiimoiGaoeltnrliuegrcicuo3PcoeooGMcoil3gmednAaaao.bao7lgaoinsrilrspecf)llnlrslEcll8vogaoaaEdsas.aooaii3hddVV-ancp.ytgsfpamQTnmolfgg23eefouchohfsnhhoedoniynh38,WefukasbelCincoedocealleT-ncaoet.dayaA..entf9nnnio,tdttiCsimAlIrcs.Poehslad7mgtn9Vh(RKthelltena6(oGSr1rdi9aCAoceFpdrrn.ios1aat,fNnt9.ul,wlocEaohru.aeautrclmPy9dausTi.nlnpetlroxpniedTHoALh4pltaztdliygwp0ronrJVdoiatnycgiB.e0eeigu..Donew)iyn.Hsarr2s.E)nau.rrrugiJroble1E.TiiaoiSon.loa.rYnKcmTifil0ol,flfnMdoccnseugoOfH4LnioEpBhiadetASeotlgDd-i-ri.ztilnmciAyx1on1ovEvikutptleTumLtt.c2apghkyd.7eassmgarmxaAahlaoeidyesieil.npeVullebtrm,f.l((moMFolBonenimdac11ooCmTnfEarc,oneTPuirHbre99il2nrkP,nhfaudlm.eerdwD.WP446Pfli..otPihennteaaietou-eee12aeocr3sartatcHtnn2CrominnniealBFaana2w))tsrldd8ylns-;---ltl...,.,.. (9)* (10) (11) (12) (13) TCIeeHESmCgaNoBCMMaV8SCT2moKHpTPnTcttnTip0ff.ogf.eaoihoioaoi.e.yaadefe.odoc)ce4r.lrlnneerlndngtLputeDslslnx.R-pi(hceitoAgc.i.ogrtc1sJAsa1ac2ietoAhyeoagDysotnc.slRbid3e1n9rCrpenecowlyaniauEcroiA0aa.8ete.4(i2tnnca,ilooiryedm,trd,L1s-nd2e7nldiadlaB.2fpVDwCJo9ugS..6sna)tapod3oooaroonTm,.4ooH-.lidn.gT2ofn0nnun32fr.RJocm6hd.,mboKydsoHyr2.,i4ffI)ee.4MAnieFfxgmE.o(ir-.a.1Vt-Adaia1DiiTWrygxA(DC0JsecReulBerA9C.1norohp-iSdonm.n2.ionc2.u4Ei9.xeu.ci.tle,,oiomwhiTcotc4cfHr0hi4rxmeufFDocliihAgan-STeMlaW)ponm6nitaod.roetya.,allph.ne(rehind)Iillsrrlelioo1eraceoE.ni.oetGdinimnnpchVs9rngVdSDEmtp.oanthhaoc.hl'4yguPcaahoMfxon.JoTceeeicilEl8srelonprdtrelVlnsnCo.otoIjnl..,).eugnrIVEte,nAnxc.phaoiarrctrtDnA2xadexi6iaioopoehHlnnxecms9slepyRunm3.ldeon,iaoyha.,dmosdn,eaFrA.l,lW,irVitHsosmnAoc(Aeonrapunp2gUaiuetxDlloVgyigEsaacrocEg2isdyldtlyfe,ss..ll..-.f...,.- 0OVV882215 :;CFTCFRCDRCCWUTPSEIRDSEONDNISETLRIOBNULTYION / ACD P ro ject States R eport - Document Noe 12850 "WHAT ABOUT KURON? " by L i. L. Coulter 1i ofi j &r > JEJ CEL TP*< XCB -- -<> ____ ------ CO _____ _ __ e*. -- -- t--eoni - -- -_. RECO DOW AC. CHSM. RES. ----------- - STAGE rlLE ----------- Cl F IL E A gricultural Chem ical Development The Dow Chem ical Company Midland, Michigan Copies to: JHALAJRPJROM........C... WDWHAJLMNIG........C.. FWDNSBWGiRWRrioacraiaaliaubivetuttyitritstsli/tolnydhtdoooainoewsnnentnroii'o'cnnk M a y 21, 1957 JVGJJGWRTCEL.../.......... E. KRNWATIEPW_.......... LFLSGBCBWCFAeimyoerraosanleyaonlhlilsensbtrenadehurennynaeryrtlnel HHGWVJRJFDTBB........o..u.mrAFWLEKSFLLtR...........SFKPMSGeCRoPFSMeemesorhoauaklaetuweydnllieelrystlldneiehdrlrsckoirooesowsxrnootentnath er "WHAT AEOUT HURON?" by L. L. Coulter - PVhioiMoa SUMMARY iInt dthifefelress sme1.arinleAlyacftiinmontohdoeiffsiHcloautwriooennr ioksnilslniinemwgilagacrrtoitwoonth,thpfartaoromtfic2mu,l4ian-ruDltye, odMfoCwsaPogoaednsy.d s2te, m4,s5-aTn.d aosahk, anadspmena2p.alnedIt-bipusockssusbiprbuelsyrhio.mr otroe raeclatitveed ocnhebmasiscwalosodanadndAmismnaotte dfeoprencodanbtrloel oonf 3 . It is not recom m ended for basal sprays. chickweeds4.as "wPerlolfaesssaiossnoacl"iautesde woneethdes inso rrtehceormn mtuernfdfeodr. control of henbit and Radapon fo5r. o vHeurr-oanll iscotnhteroplriomf barryoapdr-oledauvcet dfowr euesdes ianndcogmrabsinsaetsi.on with pionic" is t6h,,e mA mainericcoamn pCethiteimonic. al Paint C om pany.'s. "Weedone 2 ,4 , 5-T P ro NOMENCLATURE ttwncchraoaahelmndi*cfneeuhwa.smiiwhnoieTonc1uhhs9wlWiid5wslh4vhboi,neceeuaxhnilmdtawThewwnah,aosaehsostarrdDdbseteheosviiowunnaeulenltgCiovethpsaihdttedeeaddldfmbfrielotaiyrsicmnoaiadrbntlahetsbthCeeoplenroeo.tmtlnchhtaasoepcauoankhgprneahryaodevtfsesiibneaneyatnrrdtitohuceedoeasfsiumlnpwacoimhseftheadoitlbrhenslteetphyttnoieispcsaotrraemsloplm.eporsooffefdAstooreuecirrrdcecmttcsohclitreoenoadmanoictrndlhmhiogneegolgmyyn,i hcfncS"io2laaocu,smmcad4itmueeei,odsts5oyne-nifdTnooonfrFfatahAAtamdhe"micief,stofsreema.pr"rdirTemcoenIaPodntn"nuhtcacahaonmtsenmadehmaamapbf"vepoosT,erenroniePAvnncarecaecColdmhpuPodietfao'hes,unaedtdiphcpuer"o"usop2.rebd,elnua4ioncd,c"fdti25.nas,-ggieT4leav,Honce5Pnhocx-rywThomaieptssoavPioneroamnrow,iicpnancokivr"omeeoi,dnclmvaeie"ceano2p"dstn,o.lh4ywsn,aiiasttC5tihmhv-oebTemeesPWiemfcl"nvoeeo,ererinxdntuise -The active ingredient of Huron is 2(2, 4, 5-trichlorophenoxy propionic acid). faaWivnonceertysoiotousfinnhgfsieoacatutiocinaloaddlunnWssieengneopctveehodirreeuiswgSrochaonogtocnmefineemotltahywloehl naoiofnvfanfecAeaotmbsmuttearheeebanrc"ltioicssr'-ia.ehvloevqippneuhuegxeabr"svalttihetewcoedasrhtpsceitoooontnmnoeussvmsodeeaorornenidtwdth.neeatahirlmTsieasDhefmie.nisvrea.iimtIssonieoat,vnhbioeeiotwufcti Wshoaefsiemmtehfdipaci soraI nrla.tas n t wpwsoeyuehalreersrnfcheoehoruimatplnduuidsbluKalpesituociesoralsoynwtenipnohcrhtnooeisaapnr.selytavltbieoenenrieeunnfsgegedalfyesioivctuboeirlllneop,bpcoueouatdnynnndldaesnetcdhtatheicoreiencdrgowemeissqitmttueheiorrveensadxlnopeafanesmrtsiimteplhveeeserhnxpotg.ruasolltddlTaouthnbicioetsansunsisastemahtdnheedeopfrnnoreloarym e ACTION OF KURON litiwITaonnhtnhigedtitmihishsclseaaawapiantlslviymitlehettstifreseinifemcnegKslwhgcepiatuiialentnoarvhocofirnieactnntsnsathot.yilheasdett,oruhssAethprenoesnpolopfmaaiprtnenccltgicttbocmitteuoiia.amscanrtnoiysoedeemIonfso,btaescwpsofeacletlfniaeuirsgmtnKvrrtiritaeonpuswaldwrgplohyaaptwnesorhlersfiiteictirhhstmagehegtgref2iyirooou,lowllanlo4wlearo.if-atnttDwiheftgnoneTagiodrnhstdahrdicobpasto2yaitsmi,dkihnsco4liopynu,ftounhg,r52ulole-d,iptnaTn4dclang.a-s,aoDecwsatveaeninobeldmdteorriefntoi2awgtds,ssstrisw4aosorp,tcueaich5tlngpiily-oaghiiTsndtntie.goloydf. wTvboorpmttcamcihunerofiforfhhraoetsruitmmeeaoifnneypwscancngcrmmtohacntvbirmincttprbooioroaar,netsoeaewnnreniregtowynlleaia,ipyfnfnttintdioeafmnhosgaphrieilonasbfbnoralefufsndoicutmsrneneesgKotedprudta2g(rrnwee.t2ues,oavhdr)noorielo4naleniolcuynneoT-tybneliDt,drteolhthpsaestsoadniotierltoisfe.sioenetstformpiewuswmifan.ssaoeec2ontsdpeotnrthh,dpaersuedetwdt4nfaeehsiatt,atffhdrthhdtrsreryi5irtoieeacoayircs-ooulinaclmThtapfaagtuutti.cbkilhchpoitaltauthvoaaacnhnwsenituertttT.oashttliltisooyhsteylsbwlloAmneteooIietfnnnusiwfurimetsieehvnurhgsprgrsoosteutsseaetrewotl2nsalacevn,aotatiybtideotfe4titnrgwled1oere-iaeroia5a.oadsnDenpdf.vhrlkep,woiecrtinHoeflshlieodiToeyldKrceaoemelstehalchdwuatk2.eorpitetesr.,ssiaaweioomoo4rvtanumTisrnel,nensnKynelh5roocgdlai,uvwe-aaaswsdstTrsatastuitioeiewtps.mrhsislvnhnriaeepeeheea,apttlssnitslrThdicrpwyphoecseaahahowirao:oltnlaisitlweeimstnilacyathrooa(theteeceue1domnvewvts)dcfiit,eieplfehhoedtlsesfrnbeeenrpaeua,istrcan.asrevr,alueetfdtioeecshnsnynadawsthegecinoeaednrr, cri -3- lvioasmmcmenunnheateoodnlaevoacddnlninpereigigsfofissxeinhiiphcctgttioysaai.hnbr.ttaaiidtiloohttfeTiKtnnrnTlawehoeuafhriohiuarrsesocafgvittlhntohleneeyeannosoifastffutpctmoewaterttocrsiheharmtfotshseisttoncefeeaeachncorntdciiiluftoaaeactirvoftnlaaralefieefrlehndl,obreriagyncrssdswptocassafiirbahnmttmurmhrevdtrufieapatec2nchltaolruwl,ltpenryul4atpairaapr-slmerwDentepilainaotlyniriwdfauaegtienhnhndano-doaipt.corcsctfpehroostaionWnhttocrtfrjeaeavodaiuHkntuaopcnhlettseucec-eesalras2itdeoifvs,bopanniete4noblhvosca-ynaet.eDocwrsdemca,leieatwIehovctautmhnihafstintiuhreashsniaicrseaertt2ahowhhrth,ceioreeloe4tfdweegfnl,icssedrr,n5eosoc.ia-vnmutwdTrepeoiitpTvc.rshlflteoyithoedodldteLeolrerteesntrhei-eaeftae.tdf'f, C3 wmroirtteenth-aonffRwoeivtsheprr2o,au4lt-oiDnnggoeorrf 2pK,e4ur,iroo5dn-.T-t.reaTtehdis bmruesahnsisthoafttesnp rdaeylainygedc oonsets tocatnwobey e ars sj Crop Hazard with Karon Oi <35 vTtasIiKcopdeonstteofqirhuufletutGfeieorfdthcnaiooesspivracejennresemuautesese,lrenfutaneenyiiancronnntive.teiteidtntaatiaaTClissrlprrilnsfleesleaeoroygyteoxthbirslteminagheucafn.ucsuittroassdninanstmdiiEAdimtdtcFetooiwspaonnoi.r&cttausigbtdee.ratarbeshrdiauMnlIptnobensohlrwaKntdeeltthaaEreelsisuvaciayt2nxslrhtett4ylospoiseg5icKni,esasvnsaa.2thrfouevsjuiile,oufmrerd4wosprrpui,eeEitncuenrousdn5oossreuhdut-tpntddhTasieciosSuensartiwstsctiovdtahaoel,tionemetaastnilrhtns,spovoiaBsntnaibthEfnKrheu,rladaugteessurnissrSetcrtaheas.ioaphusmsrlasnueitloKtmm,airpInyic,artieseiblilcethl2ylTeauteaapl4aifsdesrvrraf5sesxeeit,dtdoactccatoyeooGfftasaomemt,nucorobnhrdoeatfnepeaitenptonohKticnudrotendseoosvu,snaistdetrbirs,tiealodiuloyoalsfnynetcnmnfwhdA,etcsoKeetci.otthnstoothuhnucaaJferbocnhbuc.otrne2ahissenud2r,enWeesyns,4qcdshie4i-suaeeeenD,d-atslenDsd,m.ntoi.tnea l cacfort2bbKirebre,fyoeooudor4cndmnrpauvo-,oreDsecminsd.ftbmlitieituio.sgowintnnSahjtiuwucihltAtnwmhOtareieccyculinoeltultdshealuspoeiueimtafnsptonlfhstifolcednlnuoyeerurtogebw,voheanecupenevtosielssrcnefasoedmensrsstommo.haualiwteernicenoniahhocsllifeytateetaafsuradbsifseansvepieplsecsecetlehthtetsocortayaa,hmttornsstftenictiaeohcomoensplaenfsdceolou,oangtgdswhinnsineriaectacifodnslaiteslw.ycielroobafnnemyfneatoerieImfaonetdcf2tlneoot,ncecaug4eoodxtstn-rchfontDootreeaeKttnes,wresmradusstheafsrhorqeioastireccu,fuinrhctlesmllyuiestoswtlrueanuieoctfvriaiauflafscseltifauoaicstoacusdtiinteesanosaeomdnuunsvsnyt,as.eaoiemlleaalltotnlylhmheaIpddenneamomytrcmrouilsiieeoeaentdondhannlcteudtsufeeionnfdrcntmetoasflatleyyd, 15995 -4- tllttptmaeehohrkaabaaaavfettdacnecetdKKicsicpiouusnaolr,rtalooofccnntrodpeotIinuemiitosssjsrhunipiansrsan,toaacasocsbfelfteeeeibelsoseater,h,ntfeopetrbowem.lueavdniaousnteeahendsvtrtessyieuifc.,nlirioopcanlmpaarel etlmogilmtcotouehacnemnuerirtnortieicafposocena,fnrrdlaoKerfupmhetrusceoaurea.nmoss,rc,nteeHdabsasoosbeine.nmerdnmectoereoEtaaabdoyxgisstefuapeitipcertthnosapvreeinoaimklttrofseit.eoibeesnanspvtesleHacetrrlhovosweemaswwlhytmdieiolcoivrrihoknkiennfesrjhtlt,uyhacoorvaofenftotenforcgchtbohecraetpeaastetpuonens es , RESIDUAL PROPERTIES OF KURON ctiwrsoseiiiesattptnhdherteinetlhtvycomeeeanpoo'ittesnttatrThacmmenphkrneeioeturpsdpastihhlitbessseynstoneeouoimnexlsxsdeytyi.lcoiacrcnfsoooIgntm-mhaoeepgprlmoeogogununaernenorngdgrdui-asestsp.lemn,.,rcms2e2T,,i4f4nhso--oiDrDstihl,aepisesl2tsore,otsnr4hiiigl,seleat5aerln-nenTtdpa.c,esehrteiMHoo.npfdCocewesPrtishelhiavavsanenetvdexre,nissitlisii,ltomvnbiaeisotntxatedeidansnsureoipefdluvfegierhx 05 BRUSH CONTROL WITH KURON Leaf-stem Sprays (Foliage Sprays): 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O il-w ater Emulsions tdhftwkdmKhooouiiheialfrnnllfefmkleodenreewarrrarcmeenfht.gouidnegoeuenteannlpgnhelaaooeoVerdlofidnlarldoebifllirniithwit-yvzhcs.iawiaoeiitslsdhtnoaiitteafbotomtselselnKoer.teasoemunteinwtlwremTeaoogwridhnutcr.ahdaek-ollsewsrlmriodehWoeaan.amngtdeisses.aderhIrpebrnsaddceseoTvipecrmahettnrooolheaennudytwsstehoneprmvoenvdamrreeisraakdaeertyly,wfedlsfisnneiebawctgcohemeeAeatfnlobKlrhtoEouhkaeafusnnnanavrtoysttneoeeifsnlrfooimaiosfcvfowesniaenteaserhipnl2knsbg.er4tedrara5udelaiwylWcsooaahrorhneeremtraesdd.kcnEvosuuooeeutsccnhetftnhtttdebaiiftraoortsueotomnneelhonnlwaowfiisnnoeraBoieidtblickhrrdlouaeiipenlneosildennhntrot C3 hU C5 CO Basal Sprays With Kuron isaSKtnttssothhpipreusutaieeccresdrthatcsosiitpyieliono,eisn.esnn,lpsdceieetdiuwrcw.WfcauasiiiihsncnrtteeWrhiiHitcsnitibhaeymhtogaeaolanwvcpbistykutaehKeoeinsoveccrlsunenlateoporeaowrkoromendnst,tncitatnesriwrwwnofesaetfdiehiioelcrcttsormehnhormwmchmuobaeoaaasornvmaunpoevoyesrtlddeenaoebpeynpal,errsddmoroaopsewvbmntpmlosbaetahoraeronalneiaueiyncrstntynaehatKtigcwalonmraeenualegesdddrerolcpooeelrrbownrwaqveiuamsnuneehtyouiatremnnshfistn^toef2caehowl,ltevionyiaetr4paeifndmtn,tgtiahdeaisn5eadbntio-itKavltuoiTstetnoisupnaisdeensrkterindoonoadewaconyfspabofn.iossoKspuatnhblhlsrouiiaFaaeaawertrsgglooodbhapeensraslaldpmapsatssfsesanroaoprtcplaoktmerarisryeaessaieebsypesanybxaarsldrsipawlasrneuseaoychassasclfch,uoislttcoor.mshaiinpnannmr,ldaeyr. WEED CONTROL IN TURF clo v ers, heKnubriotnanshdocwhsicekxwceeelldesntarpeo saspibroilbitlieems .forT hwiesedp rcoojenctrtohl aisn btueernf wrehveireew ed f1. i i i- 7- - aptqisg'3nitlluvors5aa.aiAo1n6tsroyCtsthansieDisaoinsfsspnesSueorg2teorana,iusvlta4oyuescf-scnuDrogDenRgmrO-,taoreiWpeoslpa'adssopNfreiurpescstrlTtdoiatNeOahnnwdostetr.EiroutBshAlni1penRi2eor2ff7mTcofo,64irHrsue2m,mud.s,5claayh-latTi.Iinak-toc.ndenoidsmictTiSslrmhhote.eaavcosvoenAsamrtau,biallmgrsanhouobdeesalnantebdirdbne-deoileetednn.raaeotvnrchneIdeoenlvsmydiareauemdfwsoscdeprekidntdowiuadonnsieansnedteeiedtotoolhosnnieo,finntisssFKouaaurca1nlthrclhd-o,1ent/rh2ne WpfKeluasarnssoishoninnftoagorltottthnhuAe,ertfhDftohpa. lemeClo.epuparlsoeereew.s aesnn,eeHatrison,towidmanienc.evdaetirett,hssi srtuehsscaehetonowutnleditnumbfroeafrymcisboaenltiismaoibdnilet,eerdeptdoatrosat iagacfapueiplnlyal iricnlrayettciiioomnmnetsmhteboeynmdp ro ake i;: F.-. t WEED CONTROL IN INDUSTRIAL SITES hatsopfaf2iuogpnehrs,ll4eeeeriltnenoa^-ichnDg,otwsieexmtissaawoynfunno.ghrpbddpreepemtrqrroKsForeeeuuueuduualsislrucerrartesotoimcctsdihnnittntaostiegegolwn.hnrneng,aasisttt.hshiKoww2espnbu,Reii4etteggrchahoe,rrhd5moonnan.awwv-oaphsTetntoneahIenll-nsdreesoaiecosmfmanfortsildeilaoorvdnscsrisagietnottmtaeuemiiisrnvnarspepieeldlolsegriauwiuafatednisilrrenteutteieressvpoaid.reranplaosi,glrmluwelewIaayrttsainarhetrriedtlhisyenieca'ocKhttsspn,hbos,urusmroacrouhsbonbombaaldnwandzsaebteaec-tKrnlqhlrkoyededuualbaxa.orneseoftpnuairnaeowtsfrInlcenityweyettrsofesi,iicdtloltoloulofostcmsdortuuoeohtesrsnhbeettitehaiehmrnodaioebnhtnvilhieljleaoellrprbr O WEED CONTROL IN RICE icaWupiI2nnnarsa,jee4teruATiai-oorsDersrynboekx.tcnoaaoaaonnsinrwmn,AsdtedaihpmEt2dsaMehp,mxerca4Cbconoanl,eatPdvegd5hls.aaael-eieltrLTsirantoooKontornfauciufccsmciKersroeeoooiiunfnatnnfphrhtneeorsrcetaocnohaar,tlcubneniulvgdiowosceKbhfeshine2deuret,ewihrepr4csoteesauos-ensDsiU(thawtl2rona.eea,dbedbdS4aroet.ee-atdseilDeDin.assnwd.,feMaehiaAddapItatyCberpssfeleraPrytabuoootntsesmpduaeeecnrsrbnonideyaaswotdteotuw2oe,geebt,n,erhmtaao4daono,gruisrnedcfr5nioaetot-dcoiiwTdsneno.a)tsibuwrnnCeortdgiihsanltmehalaijin,noroifoiruobcstwpithrntelnieecanetirgnhhxavocreaetoipeoivctwanwmeinpisiesniitpsvthgylteei.. i & L 15999 OOir/ I 017471 " -8 OTHER USES ltemfaroxotereplnd.lKto uaraUarcqottusoinevardtyioKitncyaawstrt.ioohs1rni-ksTn2hehpiaespirsdspocembsoudhl.ms.eoe,mwp iIilntsneatnhsetbhdoadeems,ionegmugi tirpveesedarxhonnepomvtluigeomloildrsooeeedpd,bmefcwionoeprennottsthdsrueosoebiflbnemf oloaoeersft trthpt.goiaaesvrndWrenteoochaattieqdnfgrueeeratacehwtotaiihchmts.eawmrtf 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owdao2saesit1bnvusfial%tolecvtnhyantuhed,ptixptKpsKeoo$eotumiln1lursyire1nropcn,a.otmnho,coAn5blrron0o-oiaCaewnrn-rnrpePaodydaibegbnwtrhirerepseneaiaronrsdcgesoiziwwudialdbosil,leunlaaistocjeubttatkunrederllnoasy.arractdtailhpslisumaadplawFcasnnsrwooneeatrdeerdeey2edlfiq,lfnff,"iuie4eoAseahcic-hrlvsDoeCtdroiabanev,PoalviacoeerntypomKhny,Bdpmtewueaillcrcrtenipmeorocapszpeelanesaed.l2stnicriscchodepc,oaWa1nneootuzd0,niulnleoea.3dnitaatnrr-dshdofAlswhsyeWolow".etupu,oueslesleplsedbfTcrebudtooeohergcrolnegcpiaafuteoeerlrrpsvolxm,2eooere0bfploneuelefdegtsKlrracwlupmaoiyn.umoclimdlsrdttowoe.encsinntlanehyos-ttSfacloenelouilhitsnslafdtuticirrpfoalneseiiotrrefszsirotoeudnltss COMPETITIVE PRODUCTS CONTAINING SILVEX . wci2fssoao,eum4mt hrk,e5penp.e-ooATtwuiAtm,noPdCreirTsstProshiapchehcpaiaaoinrvhdsnoeeCipnercsbeqoh"eritu.eectmiianivedcTiasaftclihilaevtailneusrttoelsPyiepasgseipoienarmrtftofgisimConail lratolovomlrmoteenuttxpdholaaiainstKtsshiyoube,atnhruouweDsnssiohienbwomauenotssioddfslexe.a"layvlrWcetOtealoeiotveuhppidorartmoounypndorerseiulnismctwe2,tese,hs4tacisencac,er5hdlo.nl-metvcTdioepaIrnnle"PyltstWyariotoifofneetpahwersiredooannsiec " , 16000 - 9- htdtchhoeuaevwstiesreielotvpspeworetlh,idilce.ltyihbreTeayvphaapehvryeaiaoavidurelaossbbtnlpeoeoertonbtodelisusupmctictcetsckhreeaesulvisyprfauitwplloarhobicnadlaetueorcvrfbtyoetarrini"nsrWiiatgnhlegheeestid-sroooenmfmv-eewaenj2atob,uy4rua,sllblii5rytnu-eeTsdrshaesPtvucwerroolhoenpiptciw.rohonhlwii,cceh"andsdois haicPsnnioarlfdowvrorperueioxmevtnideali irst4t,aiy.onctnoPheiLnessistcyotihtakes-ebedrobenlicuidAtestsrdyhCg,p.leiPcaCde,kn.osdkttuheepwTer yhaesfneoofddymerimdeCdelounhtsloehnaatmaotliettaoiscctnnhtaoiwlevwoyhefClelsoayirismreltepvparetanohcxnomciyseuloponp(ttnnderaogoenwtdrehcrueetChcaehtuhasceitdenomr amtboadhfegpeeerePonintrr)ioat,dpomperrfovoeoneadrlosumo4fcp,fetaerdrl-ya s RELATED COMPOUNDS O -si pwgatvtstmAaAohhlobidiaiCCeviriouovgssswyePrPnuahendstccntfwomalootolaeytafmimmeorsximggntmcppphecbtheieooleoteftoeAltieuunflhndrlddeennuteirccrenmddotsbohlttcte.euohiy"liievdfgwtdacsfeeoAhenoeesUisdlficnlogalntatrtttvholsrbaehlreieetcaseolcilhsamsxttiscyluiiamstolvoilnaosvdvmtfifisrpufeeotelko2yeesaxraroema,iclrao4l.tooaliovkfe-epfana.eDCtcsksrhtx.oihopmhil,cmnIeovcretooongemeaImcnsdnsxsnotmviteusd,ecrmaee,scoraadrmp2ciptllpyhtd,ioetlasoiiDoe4ucwtnslwi,ni-etqsooedcdrpveouunswioi,revkc-ifl,outdhlaehoieodnw-inrrfilcpho,uttgpehsoeamarcrvrasortdodaeamek.epeebncwcc.hcvaatttteeieiokTebnvdfwnHellnohiteobeostlhodeorepyyxwarwtissythtetr,tsoeeeahktpevhvpigtenidesnetereyaotciotryrhwrsaii,tpahdsrcri.felisaupeoioeulvtdmoynyencneTsthleoiliascuhaianmiriskissisnruebasepsaseaicoleao,lacymivniuscdtttDleaiinyaoty,avsnnhdommtfadwatehahtpitracesiailnsdiatnflog^. CONCLUSION Prim ary Uses for Ruron Are: the populat1io. n.R iIgthits-oaf-wsuapyerbirourshprocodnutcrtolfowr htheries pouakrpaonsed./o r m aple dom inate 2. As an additive to Radapon for bro ad -leaf weed and brush con trol in industrial vegetation control. O klahom a a3n. d RTaenxgaesl.and brush control by a ir application in M issouri, A rkansas, 16001 -10- 4. Weed control in rice. users. 5. Control of re sista n t and general w eeds in tu rf by professional 6. Bidweed control by spot treatm en t. Wwpa uiegsllohc^aadilntwDfnaoooyrwwsKshpupsarreeoovecdnei fucihsclcoeat msaufrsoehleyrascdswopwlmhiemhecperieireatteelitiditpiostrdnoege,bxvrlcteeehealmeoltspes.wsm, taeyapnnotidstaewnondept ieassnlha olufeoussreldspu smraortameok,oeetasieontvandebrwliyni shhteihlfeetfhowpirstea statos. OOIV 1 017173 16 I * 'r r ?. i t l i P l o o I-4 }-* M @ W ^SMJCAL COMPANY DOYIJ027211 XaZySLA2M5.) i960 ?. Ritty Agricultural Chemisai Development Abbott Road Building cowoents on bollxtin sntitlxs. "aquatic tooeation control WITH KURON" BY MART 0 . ILT3R I have reviewed the bulletin and would like to sake the following auggeatlons In the section entitled, "Safety to Uaer". Kuron herbicide Is low In toxicity and presents a low degree of hazard In handling and use. -V When Kuron herbicide was fad by Intubation to groups of 7~ various anlaal species, the LDe0 values were found to h as follows: rat, 1070 m g A g ; guinea pig, 850 rabbit, r oA z8 5 0 m g A g i aouse, 210 m g A g and chicks, 2000 m g A g - From these data. It aay be concluded that there should be no pro blem from Ingestion inoldental to the handling and use of o this product. If large quantities are aswwaalllowed, accident- ally or willfully, some injury night result However, the* llkellKood o f serious in^urjr is remot^e"! TlTiSeverthelssa, Xuron oO m Z3 herbicide sffould not be wHiare children or livestock have access to It Cattle, sheep, swine, ducks and chickens have oonsuned water containing Kuron herbicide at 50 ppn over a four week period with no adverse effects as determined by water oonauaptlon, body weight gains, and gross observations, Including gestation and parturatioo in sheep. These data Indicate that foliage or water treated uith Kuron herbicide, as recommended, should not present a hazard from ingestion. Skin irritation tests conducted upen rabbits have Indicated that Kuron herbicide and Its dilutions are slightly Irritat ing, upon repeated prolonged contact. In these studies, there was no evidence of absorption through the akin In acutely toxic amounts. The observation of reasonable care and personal cleanliness practices should be adequate to avoid skin diffi culties . Kuron herbicide, when diluted to one per sent with watar, caused no primary irritation nor allargenlc responses when applied to P. Ritty 2 May 25, i 960 \ the akin of 50 human volunteers using a repeated insult technique. One subject did develop a olid fatiguing res ponse. In addition, the product was "patch tested" on a second group of 50 human subjects at concentrations up to 50 per cent without cutaneous reaction. Sven when applied G K) K> undiluted to the skin for 2 hours, it caused no. skin response. 10 Thus, it may be concluded with a high degree of assurance that when used as directed, this product should cause no skin irritation or skin sensitization responses. When tested on the eyes of rabbits, Kuron herbicide and its solutions produced moderate pain but only slight irritation. Thus, this product presents no unusual hazards from eye c o n A tact. However, suitable eye protection, such as safety glasses, may be worn simply to avoid the discomfort that might result from contact. n --- - I u s e zunderstand that many local and state laws governing the O of hazardous substances require that all literature giving -n directions for use must include a copy of the precautionary -- label. While Kuron is not highly hazardous, I believe this O is a good practice and therefore I recommend that the follqw-111 ^ ing section be added to the bulletin: j2 Recommended Precautionary Labeling for Kuron Herbicide ~ CAUTION MAY CAUSE SKIN IRRITATION Avoid contact with eyes, skin and clothing If there are any questions concerning tne above, please call me. Marie A. Wolf Biochemical Research Laboratory 1701 BJildlng Phone ME 6-2776 MAW/jd cc: L. L. Coulter M. G. Wlltse 18004 //+.r ir AQUATIC VEGETATION CONTROL WITH KURON* 11 0141 by Marie a. Viltae * THE- DOW CHEMICAL COMPANY 6 3 - t o a DOWJ 027202 Aquatic weed growth has become an increasing problem in recreational waters of the eastern half of the United States. Vegetation has restricted utilization of waters for such pur poses as bathing, water skiing, boating, and In some instances have destroyed the normal beauty of aquatic areas. Fish pro duction has often been limited by excessive growth of water weeds. A number of control methods have been employed with varying degrees of success. Mechanical contrivances have ranged from under water cutt bars to hand rakes. Although these siechanlcal methods are ofte effective for a short time, regrowth from roots or rooting of stem fragments often Increases the problem. The method Is generally laborious and provides only temporary relief. Sodium arsenlte has been used as a herbicide for several years. In same areas, particularly static waters, this well known chesdnal has given outstanding results. Principle limitations to Its use have been Its Inherent toxicity, resistance to dec&n* position and failure to control a broad range of vegetation. Several workers have been actively evaluating products which would control submerged aquatic weeds and overoosM the limitations of previously existing methods. The New Jersey Division of Fish -- --i' and Game inaugurated a five-year research program In 1951 financed by Dlngell-Johnson funds to find an aquatic herbicide (8). In the course of this work, Kuron/was found adaptable to this problem and seemed to offer control comparable to sodium arsenlte (8). Karon contains the active Ingredient allvex 2(2-4,5-trichlorophenery) propionic acid as the propylene glycol -2 - DUWJ 027203 butyl ether ester and acts as a plant growth regulator. Aquatic Weeds Controlled ,1 Early tests Indicated that Kuron at 5 quarts per acre foot /\ would control many of the troublesome submerged aquatic weeds in the northeastern United States (1,2,3,4,8). Experimental tests in 1957 and 195^ in several sections of the country evaluated the effectiveness of this concentration on several aquatic weeds. Some tests were conducted at reduced concentrations by certain workers (2). Commercial applications in 1958 and 1959 contributed additional performance information for controlling certain spedies. The following list summarizes some of the weeds controlled by Kuron. Aquatic Weeds Controlled by Kuron at 1.25, 2.5 and 5 quarts per acre foot ^ /iCuron/1 1/4-quarts/acre foot or less ( L)t-Y ^ White water Lilly- (Nymphaea spp.) Pickerel weed ^ (Pontederla cordata L.) n O z c oC m Z$ A t (^Kurgnr^2.5 quarts/acre foot or less Yellow water 14f*$l. (Nuphar spp.) Mud Planttn (Heteranthea- spp.) Water Milfoil (Myrlophyllum heterophyllum) quarts/acre foot or less C Bladdei^jyort (Utrlcularia spp.) Water^ahield (Brasenia 'tohreberi) Cpontail (Ceratophyllum demerj^um) Fanjrfort Waterweed (Cabomba carollniana) .A S A ****** s. (fVrxlsa canadensis ) Variable pond weed (Potcttogaton dlverayfojl (Potoaogeton aaplifol^ujs D01YJ 027204 3- - Burly .Pondweed Spike Rush Tape grass Water_^taiv'wj^rt Soft rush Bulrush Bur Reed (Najas flexllis) (Eleocharis spp.) (Valllsnerla amerlcana) (Callltrlche spp.) (Juncus effusus) (Sclrpus americanus) (Sparganlum spp.) In some treatments, these weeds were controlled at lower concentrations, hut there were not sufficient tests to indicate consistent effectiveness at the lower rates. Treated areas observed two years after treatment indicated a continued control over this period of time. In total treatments on ponds and lakes with Kuron at 5 quarts/acre foot 2 years control has been obtained in some instances. Application Technique n O z n Emerged species were controlled in many instances by using Kuron at one gallon per 100 gallons of spray solution applied to m Z the emerged foliage as a thorough wetting spray. The applications for the control of the submerged aquatic weeds were generally applied by diluting the Kuron at 1 gallon in 10 to 40 gallons of water and directing this solution on or into the^ water^ Pro- -- , --*^4 Cr-M-r<v> >i f 1"-!* portioning pumps were often used to deliver the-Knrnn soliittniT tcj^bocag which would distribute the Kimm solution over a wide swath. Uniform distribution appeared to be desirable to allow a lethal concentration of the Kuron to come In lmaedte contact <=^L withythe vegetative growth. Injection of the undilutedQKuronJformulation^was used in some equipment, but on a limited basis. 16007 -4- Environmental Effects' Kurort /^pplications/appeared to be most effective if treat DOW-1 02^205 ments were, made during periods of active growth. Treatments applied when water temperatures have been 65P or higher have been most effective. The water temperature may not influence the reaction of the chemical to a significant degree, but the aquatic weeds may be in their moat active growth at these higher temperatures and thus more susceptible. Undoubtedly, the most active growth periods vary for the various aquatic weed species. Applications with Kuron have been most effective on sub merged aquatle plants in lakes and ponds where there is no or limited water movement. Less satisfactory control of some plant a has been observed where water currents replace the treated wate: O soon after application. Translocation has been demonstrated j 2 in water lilies where applications to the leaf surface has caused a herblcldal effect on the rootstock. However, some aquatic plants have only prlmatlve vascular systems which may O o rrt O 2* not be functional and translocation to root areas probably is not important. In these plants, a lethal concentration of Kuran \to contact all the vegetative portions of the plant which J are capable of growth or reproduction 'may be required.\ Adequate m i si !-- m aiuuiiiniiu pimii iu ausimiiu u n m a r et or LTlb KU1TJ1U Ul uue4-- 0 Although the exact minimum contact or exposure time required is not clearly defined, 46 to 72 hours exposure to treated water has given control. Truchelut and Williams (7) compared the effectiveness of Kuron for controlling coontail (Ceratophyllum demersun) in greenhouse tank experiments at three pH levels and three con- eeatretloos of oalaliM ions. Karoo was meet effective eo 16008 -5 - DOWJ 027206 ooontall growing in slightly acid water. It was- also more active on coontail growing in water with 250 and 500 ppm of calcium i ion than in water with no calcium. In these tests, the effect of calcium was not differentiated from a possible effect of chloride ion which was added in equivalent amounts. Field plot treatments and ocnmercial application have been only slightly better under acid water conditions compared with treat ments to neutral or slightly alkaline water. Perhaps the water pH is only important in water situations with a low level of calcium ions or similar dissolved ions. Safety to Fish and Other Aquatic Organisms The experimental treatments to plots and ponds have oaused no fish injury at(Kuron)concentrations/of 1.2 5 to n O z 5 quarts per acre foot.Cceaserlcal applications at concentrations o m of 5 quarts per acre foot or less have given no appreciable fishfili o O * in numerous treatments throughout the country. Slight fish kill has occurred in some instances where applications were made at higher concentrations. The higher concentrations scmetlams occurred In shallow areas where the spraying equipment could not operate properly *nd thus higher concentrations were developed. There ham, been no fish Injury in over 99Jf of the treatments applied... Rapid Incorporation of the spray solution particularly those associated with rates In excess of 5 quarts per acre foot of Kuron should be avoided where fish kill cannot be tolerated. Pierce (4,5,6) found that(lCuron)applicatlons/had no In fluence on oxygen content in treated plots. Aquatic weeds treated with Kuron normally deccsqpose slowly, In most situations 10 to 21 days are required for decomposition. This slow decom- 1S0G9 - 6- DOVILI 027207 position apparently does not lower the oxygen content of the water. This is & problem with some aquatic herbicides which give rapid kill of weeds. Pierce also reported that Kuron treatments showed no effect on population of benthic organisms represented by the following groups; Annelida, mostly leeches; Molluscs, including 7 species of Gastropoda and 1 species of Pelecypoda (Sphaerium); Amphipoda; Insects, larvae of mayflies, damsel flies, dragon flies, midges and bedlesi.. ^(kKuutroo^^i#Applications temporarily decreased populations of stane plankton, but within two weeks after treatment the populations were equal to untreated areas. These plankton consisted of fifty identified species in the following large groups: Myxophyceae, Chlorophyceae, Desmidaceae, Diatomaceae, Flagellata, other Protozoa, Hematoda a Rotifers, Annelida, Crustacea. There was no deleterious effect on large aquatic vertebrates such as frogs and turtles in the treated areas. Prolific algae growth is often a problem soon after treat n O z "71 o oO m Z3 ing aquatic weeds with sene aquatic herbicides. Algae growth 3 4has no^n^rmally occurred until to weeks after^Kurop treat m e n t ^ T h e delay In appearanoe of algae apparently is associated with tha slow kill of the uatlc weeds and thus the delay In release of nutrients; e water from t k ? ' fi Kuron^ia a(relatively safe material to use. When Kuron V* was fed by intubation to groups of various animal species, the U p v a l u e s were found to be as follows: rat 1070 ISifeg; guinea pig, 850 mg/kg; rabbit 850 mg/kg; mouse, 2140 mg/kg and chicken, 2000 mg^cg. Thus Kuron is low in acute oral toociaity. A-/ Q 07J Z 0 i'lifm in-o ther-teat, Cattle, sheep, cks and chickens consumed water containing(50 p Kuron^over a four-week No adverse effects \were* demonstrated in-any-uf Lite- spetflwa of animals tooted as- determined by water consumption, body weight gains, and gross observations, including gestation; and parturation in sheep, i-- Results of dermatological Studies indicate with a high degree of assurance that Kuron will not cause skin irritation or skin sensitization when used according to label directions, Generally accepted methods of handling agricultural chemicals associated with good personal cleanliness should be sufficient for the use of Kuron. Effect on Water Use Kuron may remain in water for 3 to 4 months after treat- j 2 ment where no dllutlnn occurs. An 3d acre lake was treated in New York after the water level was lowered 2 feet. No flow occurred through the outlet until 3 months after treatment o m z D o 3 In analysis of the lake water 30 days after treatment, 2.4 ppm of sllvex from Kuron was present, essentially the same amount that was applied. Analysis of the lake water 70 days after treatment showed 2.1 ppm of sllvex present. Samples of water analyzed 100 days after treatment and there after showed no Kuron present. Chemical analysis.of,the, bottom mud indicated U JtcciJu * no build-up of Kuron. Since Kuron^la an organic compound, the components would be expected to be bacterlologlcally decomposed principally to the elements carbon, hydrogen and oxygen. Sllvex acts as a growth regulating compound on terrestrial broadleafed plants and is used as a stop-drop treatment prior DOWJ 027209 -8 - to harvest of apples at concentrations of 10 to 20 ppm. Al though 2 ppm of sllvex as used for aquatic weed control might not cause injury if sprayed on some broadleafed plants, some susceptible species may be affected. Accordingly, it is suggested that water treated with Kuron should not be used for spray purposes or for irrigation during the season of treatment until more information is available on the possible hazards to crops. 1 n O Dow Summary Kuron^s|^)^ffectiv^/aquatic herbioide^on several sub Z i merged and emerged aquatic weeds. Applications to still wat< at 5 quarts per acre foot are suggested for general aquatic weed control. Lower rates are effective on certain specios. Conditions for growth, pH and dissolved ion oontent of water may influence the effectiveness of Kuron. The low mammalian toxicity, slow actl<^, and safety on fish food organisms are desirable propertieafo Kuron^use as an) aquatic herbiolde. ? Literature Cited DOWJ 0 2 7 2 1 0 1. Boschetti, M. M., "yield Testing of Kuron as an Aquatic Herbicide In Massachusetts," Proc. NEWCC, 13:315-321. 1959 2. Cortell, J. M., "Re-Evaluatlnn of the Concentrations Required for Effective Aquatic Weed Control with Silvex." NEWCC 14 :478-482. i960 3. Hall, W. C., "Control of Various Aquatic Weeds with Silvex." Proc. NEWCC 14:476-477. i960 4. Pierce, M. E., "The Effect of the Weedlclde Kuron upon the Flora and Fauna of Two Experimental Areas of Long Pond, Dutchess County, New York" Proc. NEWCC 12:338-343. 1958 n 5. _____________ "Further Studies of the Effect of Kuron Upor O the Flora and Fauna of Long Pond, Dutchess County, N. Y. z -n o Proc. NEWCC 13:310-314. 1959 4: O m O 6 . _____________ "Progress Report of the Effect of Kuron upo^i Z the Biota of Long Pond, Dutchess County, N. Y." Proc. NEWCC 14:472-475. I960 7. Truchelut, 0. B., Williams R. C., "Sosm Observations on the Influence of Dissolved Ions on The Effectiveness of Phenoxy- type Herbicides on Submersed Aquatic Weeds." Proc. SVCC* ^ I960 3 3! - 8. Youngs^:'[ J t . 'ii- "A Preliminary Report on Controlling Aquatic Vegstatlon; In New Jersey with Kuron." DOWN TO EARTH, Spring 1958 9 . Younger, R. R., "Progress Report on the Use of Kuron, 2,4-D and 2,4,5-T? Granules on Aquatic Herbicides." Proc. NEWCC 13:322-329. 1959 16013 aTs M g ^SMJCL COMPANY DOYU0 27211 MIStAND itey 2^ I960 ?. Bitty Agricultural Chemical Development Abbott Road Building COMMENTS ON BULLETIN XNTIYLJED, "AQUATIC VSQSTATION CONTROL WITH KUHON" BY MARK Q. WILT I have reviewed the bulletin and would like to sake the following suggestions in the section entitled "Safety to User". Kuron herbicide is low in toxicity and presents a low degree of hazard in handling and use. When Kuron herbicide was fed by intubation to groups of various animal species the LD,-0 values were found to as follows: rat 1070 mg/kg; guinea plg 850 (^7kg; rabbit 50 mg/kg; mouse 210 mg/kg and chicks 2000 mg/kg. From these data It aay be concluded that there should be no pro blem froa ingestion Incidental to the handling and use of this product. If large quantities are swallowed accident ally or willfully some injury mlghb result. However the llkeliHood of serious injury is remote^ Nevertheless Kuron herbicidesfiould not be left Fere children or livestock have access to It. Cattle sheep swine ducks and ohlckens have consumed water containing Kuron herbicide at 50 ppm over a four week period with no adverse effects as determined by water consumption ~ body weight gains and gross observations including gestation and parturatlott In sheep. These data Indicate that foliage or water treated 1th Kuron herbicide as recommended should not present a hazard from Ingestion. Skin Irritation tests conducted upon rabbits have Indicated that Kuron herbicide and Its dilutions are slightly Irritat ing upon repeated prolonged oontact. In these studies there was no evidence cf absorption through the skin In acutely toxic amounts. The observation of reasonable care and personal cleanliness practices should be adequate to avoid skin diffi culties . Xurcn herbicide when diluted to one per cent with water caused no primary irritation nor allergenic responses when applied to 16014 D M lU 0 2 7 2 1 2 P. Ritty 2 May 25j i960 the akin of 50 human volunteers using a repeated Insult technique. Okm subject did develop a mild fatiguing res ponse. In additionj the product was "patch tested" on a second group of 50 human subjects at concentrations up to 50 per cent without cutaneous reaction. Sven when applied undiluted to the .skin for 2 hours, it caused no- skin response Thus, it may be concluded with a high degree of assurance that when used as directed, this product should cause no skin irritation or skin sensitization responses. When tested on the eyes of rabbits, Kuron herbicide and its solutions produced moderate pain but only slight irritation. Thus, this product presents no unusual hazards from eye con-___ A tact. However, suitable eye protection, such as safety glasses, may be worn simply to avoid the discomfort that might resul from contact. I understand that many local and state laws governing the ujse 2 of hazardous substances require that all literature giving directions for use must Include a copy of the precautionary label. While Kuron is not highly hazardous, I believe this is a good practice and therefore I recommend that the follqw lng section be added to th bulletin: flecoamended Precautionary Labeling for Kuron Herbicide CAUTION WAY CAUSE SKIN IRRITATION Avoid contact with eyes, skin and clothing If there are any questions concerning the above, please call me. 'V Mark k\ Wolf Biochemical Research Laboratory 1701 Building Phone ME 6-2776 MAW/jd cc : L. L. Coulter M. G. Wlltse 16015 DOIYJ 027213 r< sj Sil "Vj rri ft) c"< Ii i- M. G. Wilts e Ag. Cham. Dev. ARB Paper: Aquatic Vegetation Control with Kuron Midland, Mich. May 13, I960 This paper is approved for outside, presentation and publication. We are retaining ^ copy (ies) for our files. o O z -n --O o i i > sfm 36-B-6602 'T-* To be Presen-te1d ^'***' E . Monroe Applications Liaisor. Center To be Published; J fa w handouts to interested ACD cooperators from ACD available literature file. c c : D. M. Plum m er M. Ondrus 16016 f ROUTING SHEET FOR THE RELEASE OF TECHNICAL INFORMATION CINTRAL RISIARCH INOIX 344 wilding. Midland, Michigan in order to safeguard the Interest of The Dow Chemical Company and its authors, all talks, papers, publications, a rtic le s ,' news releases, etc. for release outside the company must FIRST BE APPROVED. Technical information must be approved by Midland Central Research Index and other m aterial by the Public Relations Department. INFORMATION TO BE SUPPLIED AT SOURCE: o TitleofproposedTalkorPublication: Aquatia Vegetation Control with Kron ro Authors: Or. Hark G Wlltse Submitted By: D r # Q W lltS O Date: 0 To what process is the information in this paper related? Hone Is this information covered by patents -- patent disclosures? Yrtr-- Deadline Date: n o z Where and when talk is to be presented: Hot applicable. gaacuTnievctr iKvciaoeA.-icx O R 25 196 probablepubucationordistributioo: 500 copies to be made for use as Dow handoutf to Interested ACD cooperatora from ACD available literature HCTMi year tohtontom toto m tm m ym m kmmt, to. tototo. / toto 1-toiwwlCTwill wmi uw to. mtowtodewtoi Approved By Comments Dept, Head ROUTING DOW Dow International ^ DALopiw'mprioItnvatet-eidor-nfAso:mr re"erliecaanse --b--y-: - __ J r/ - ' j __c . . . . . . / . / __ ' '> ~ /^ ) au-i mnn n 1.1.1. ni-u om 16017 : A\\ ! ( yt THE D O W CHjEMICAL COMPAI\r8j4 MIDLAMD, Michigan March 26, 1965 -C3 H. L. Gordon, M. D. Medical Department 607 Building cc : B- B- Holder, M.D., Medical Department, 607 Building C. G. Kramer, M.D., Medical Department, 607 Building H. H. Gay, M.D., Medical Department, 607 Building R. D. Stewart, M.D., Medical Department, .607 Building K. J. Olson, Biochemical Research Lab., 1701 Building L. G. Silverstein, Biochemical Research, 1701 Building H. R. Hoyle,^ Biochemical Research Lab., 1701 Building E. M. Adams,\ Biochemical Research Lab., 1701 Building V. K. Rowe, Biochemical Research Lab., 1701 Building S. E. Sadek, 'Biochemical Research Lab., 1701 Building C. P. 0 'Hare, biochemical Research Lab., 1701 Building T36 2*5-66681-6 b cc Co THE INEFFECTIVENESS OF WASHING AS A PREVENTIVE MEASURE IN THE FORMATION OF FOLLICULITIS IN THE RABBIT EAR FOLLOWING REPEATED APPLICATIONS OF 2,3,7,8-TETRACHLORODIBENZO-p-DIOXIN IN CORN OIL Problem To examine the effectiveness of washing with soap and water as a prophylactic measure in the control of folliculitis produced in the rabbit ear by repeated applications of various .concen trations of 2 ,3 ,7 ,8-tetrachlorodibenzo-p-dioxin in corn oil. A previous report (T36.25-66681-2) summarized the effect of washing the material from the ear when applied in benzene as a solvent. The material is relatively soluble in benzene. It was of Interest to employ similar techniques by applying the dioxin in oil in which it is essentially Insoluble. Materials Used 0.01 Per cent and 0.001 per cent 2,3 ,7 ,8-tetrachlorcdibenzo-p- dioxln Isolated from caustic Insoluble oil. Solvent -- Corn oil Soap -- DJ.ai Tap water 16018 Dr. Gordon 2 March 26, 1965 Washing Procedure Ears were thoroughly washed with rich soap lather for 30 seconds and subsequently rinsed in copious amounts of freely-flowing tap water, after which they were blotted dry with'paper towels. Exposure Times Selected For Study (l) Five seconds (time taken to uniformly spread solutions de scribed above on rabbit ear). (2) Two hours. (3) Four hours. Cl Experimental Procedure The effectiveness of washing with soap and water as a prophylactic measure was studied in the lab, by repeatedly applying the solu tions described above to rabbit ears -- 0 .1 cc/ear/day -- and allowing the material to remain for controlled periods of time before washing. Two animals were used to demonstrate each point represented by a chemical concentration and a particular exposure time. Controls for each chemical concentration and for the sol vent were incorporated into the study. A total of 18 animals were used in the evaluation. Results And Conclusions Results of this study indicate that concentrations as low as 0.001 per cent 2 ,3 ,7 ,8-tetrachlorodibenzo-p-dioxin in corn oil produced a discernable folliculitis as a result of sixteen applications in 24 d V/hen compared to a previous similar experiment in which benzene was incorporated as the solvent, results Indicate that the use of benzene hastens the development of folliculitis. Under the conditions of the experiment it appears that washing with soap and water is quite ineffective as a preventive measure even when the dioxin is applied in an essentially insoluble form. C. P. O'Hare K. J. Olson Biochemical Research Laboratory Biochemical Research Laboratory 1701 Building 1701 Building sjl attachment 16019 Solution Strength 0.01# 0.01# 0.001# 0.001# Number Of Applications 16 14 16 16 Days Exposed 24 24 24 24 Washed No No No No 0.01# 0.01# 0.001# 0.001# 11 17 At once 14 20 At once 16 24 At once 16 24 At once 0.01# 0.01# 7 13 2 hours 6 11 2 hours '0.001# 16 24 2 hours 0.001# 14 20 2 hours 0.1# 0.01# 16 24 4 hours 16 24 4 hours 0.001# 16 24 4 hours 0.001# 16 24 4 hours Corn oil Control Corn oil Control 16 16 24 No 24 2 hours 16020 Summary of Results Ear Appearance First Appearance of Follicullt Applications Days Expose Moderate-severe folliculitis Severe folliculitis Slight folliculitis Slight folliculitis 12 12 16 16 18 21 8k 2k Severe folliculitis Severe folliculitis Slight folliculitis Very slight folliculitis 9 12 16 16 13" 21.8k 2k Severe folliculitis Slight folliculitis (Animal died) Slight folliculitis Severe folliculitis 6 10 6n 16 2 k 11 17 Mouerate folliculitis 15 21 Moderate folliculitis Slight folliculitis Slight folliculitis 15 16 16 21 22 kk O.K. O.K. D01V 092087 FOR DOW PERSONNEL ONLY NOT FOR OUTSIDE DISTRIBUTION 1714 /> 7 ^ 3 `CD" Project Status Report - Document No. 16793 \kIi . . f AQUATIC VEGETATION CONTROL WITH KURON i- I(i by . L. L., Coulter June 16* 1958 Copies to: J..F. Maddox W. F. Richarda J. W. Britton ACD Circulation P. M. Ritty H. A. Nation R. L. Warden J. W. Gibson. R. Raynor -J. R,. Fisher ... M. 0. Wilts*: '. "* F. S. Pearae J. S V/ilson B. Seeker S. A. Gendregake J. E. Johnson J. K. Leasure A. J. Watson A. W. Swezey R. W- Colby W. W. Allen E. T. Coon E* M* Lutz H.- L. Smith (4) V- K. Rowe W* R. Mullison J. A. Kelly W. VanValkenburg D. L. Conner H. H. McIntyre T. Foster B. L. Fayerweather B. Dosser `]vTwS'wrf^i2.y~i-''visr- - 16021 r 8 8 0 2 6 0 1 MOQ DOW CONFIDENTIAL | AQUATIC VEGETATION. CONTROL WITH HURON by L. L. Coulter Summary Huron at one gallon per acre foot of water has given excellent control of water milfoil in the east. The potomagetons as- a group have been resistant to this- dosage. No fish kill has been noted at this rate. This product will not be recommended by The Dow Chemical Company for this use in 1958 but.an intensive development program is proposed to define the limitations and provide the basi3 for labeling in 1559 Introduction Huron has been evaluated for emergent and submergent aquatic weed control by a number of experiment stations during the last two years. Investigation has been most Intensive in New Jersey. The work there was reviewed by Roy Younger of the New Jersey Fisheries Commission in the spring issue of DOWN TO EARTH. Some of the re sults have been rather spectacular, and in the absence of any other truly satisfactory aquatic herbicide, Huron has naturally stirred up a great deal of interest, particularly In the eastern areas where the problem Is severe. This Interest has been Intensified by the several papersl>2,3 on the use of Huron which have been publishedthis winter and by the discussions which have taken place In the various weed conferences and fishery society meetings. With this interest manifested, it is logical to expect that many people with aquatic weed problems will be interested in the use of Huron for aquatic weed control during 1958, and we will.be under pressure to supply Huron recommendations and guidance for It3 use. This report is prepared to bring together the information that we have and to point out certain information that we do not have In order to facil itate proper handling of the anticipated inquiries. A section la also devoted to the development program and its objectives. 1. "A Preliminary Report On Controlling Aquatic Vegetation In New Jersey Witte Huron", Younger, Roy R. DOWN TO EARTH 13:^ Spring, 1958. - 2. "Aquatic Weed Control in Kentucky and Preliminary Research With Certain Herbicides Used For Their Control", Charles C. Bowers, Proc. N.C.W.C.C., December, 1957- 3. "The Effect of the Weedicide Huron Upon the Flora and Fauna of Two Experimental Areas of Long Pond, Dutchess County, N.Y. Pierce, Madeline E. Proc. N.E.W.C.C., January, 1958. 16022 DOW1092089 Performance Kuron Is applied In a manner which permits the build up of a given concentration in .the water of the entire treated area. Thus, a dosage of two ppm is an application of Kuron sufficient to give a concentration of two ppm of silvex equivalent in the entire pond or lake. Obviously,' the concentration in the spray tank Is of little significance. Many emergent and submergent aquatic plants have been reported satisfactorily controlled with Kuron at concentrations of two ppm acid equivalent or less. These are: white water lily, Nymphaea; yellow water lily, Nuphar; mud plantin, Heteranthera; waterweed, Anacharls; water milfoil, Myrlophyllum; bladderwort, Utrlcularla; arrowhead, Sagittaria; water shield, Brasenia; fanworFJ Cobomba; wild celery, Valll3irla;-coontall, Ceratophy1lum. Of this group, water milfoil or Myrlophyllum and white pond lily, Nymphaea are probably the most susceptible. The Potamogetons appear to be quite tolerant to Kuron. Unfortunately, this is a major aquatic genu3, and while it has not been the dominant trouble species in New Jersey, it Is In some areas, and it could rapidly become a real problem after the more suscep tible species have been controlled with Kuron. We do not have sufficient information to know what concentrations are required: to control Potamogetn. In fact, there is some doubt that this weed can be practically controlled with Kuron.' Duck weed, Lemna minor, is tolerant to Kuron as it is to most herbicides. Some satisfactory control has been reported by multiple application within one or two day periods so that as the plants are shifted about the pond new .plants which were previously protected from an application can be sprayed. However, even with this promise, we cannot feel that Kuron is going to be the answer to duck weed. It has .not shown any promise as an algaeclde. Speed of Action*:. Hie reaction of most plants to Kuron, particularly submerged weeds, ia very. slow. It ordinarily requires at .least seven days before response is noted, and at the end of*two'to*three weeks, some open areas may be evident as a result of a "settling1* of the. weeds. Milfoil usually disintegrates in about three weeks, and in about one month control-Is obvious and there.may.be a breaking off of large masses of plant tissue which float ashore. This slow action is desirable from a biological standpoint, since the gradual decomposition of organic matter does not create an oxygen shortage in the water as may happen when vegetation Is killed quickly and the entire ma33 disintegrates within a short period. This can happen when sodium arsenlte is used and may. be accompanied by high \ ; t ^ j | \ ! f . 16023 DOW1 0 9 2 0 9 0 t fish mortality a3 a result of low oxygen supply. .From the selling 1 point of view, of course, slow action nay be somewhat undesirable ] since nest folks are anxious to get results quickly. Nature of Action Kuron probably, has the sane physiological effects on aquatic weeds that it has on terrestrial plants. However, the manner of getting it into the plant is quite different since most of the growth is submerged. Thus, by building up a concentration of Kuron in the water surrounding it, a plant is literally bathed in herbi cide, and even though translocation, which may be very limited in these primitive plants, may not occur, lethal action can take place through absorption over the entire exposed area of the plant. We do not know if aquatic weeds as a group are more susceptible to Kuron than they are to other phenoxy growth regulators. However, we feel that one of the reasons that Kuron has been more effective is that it is more persistent in water than either 2,4-D or 2,4,5-T. This has been reported earlier by Barrons in GH Report, "The Rela tive Persistence, of Six Substituted Phenoxy Aliphatic Acids in Pond Water'*, dated February 28, 1951. This work showed conclusively that 2,4-D and 2,4,5-T both decompose rapidly in pond water con taining active micro-organisms, while Kuron persists. This has been verified by analysis of test areas last summer, where no change in Kuron content wa3 indicated two months after treatment. Thi3 longer persistence gives a longer and more continuous exposure of plants to the herbicide. Methods of Application In most of the work that ha3 been reported to date, Kuron has been diluted at a rartio of 1-.40 in the spray tank, and then this diluted spray has been applied to the surface of the water. This has been effective on both emergent and submergent species, however, presumably there are several other methods which might be used to apply Kuron. These would include injection beneath the water sur face, if feasible, and spraying over the surface with other dilutions that would be practical for various types of equipment. In any case, th* main thing is to attempt to build up a lethal concentration in'the water. There is no evidence that emergent species such a3 lily pads are controlled better if the surface is sprayed as compared with the injection below the surface. However, in many cases this would be the most feasible way to make the application. Methods of injecting the chemical directly into the water without pre-mixing are being Investigated. . ' fce. i.. "t 16024 DOW1 092091 _3. 1DOW CONFIDENTIAL \ fish mortality as a result of'low.oxygen supply. From the selling point of view, of course, slow action may be somewhat undesirable since most folks are. anxious to get results quickly. Nature of Action Kuron probably has the same physiological effects on aquatic weeds that It has on terrestrial plants. However, the manner of getting it. into the plant is quite different since most of the growth is submerged. Thus, by building up a concentration of Kuron In the water surrounding it, a plant 13 literally bathed In herbi cide, and even though translocation, which may be very limited in these primitive plants, may not occur,-lethal action can take place through absorption over the entire exposed area of the plant. We do not know If aquatic weeds as a group are-more susceptible to Kuron than they are to other phenoxy growth regulators.. However, we feel that one of the reasons that Kuron has been more effective is that it is more persistent in water than either 2,4-D or 2,4,5-T. This has been reported earlier by Barrons in GH Report, "The Rela tive Persistence of Six Substituted Phenoxy Aliphatic Acids in Pond Water", dated February 28,-1951- This work showed conclusively that 2,4-D and 2,4,5-T both decompose rapidly in pond water con taining active micro-organisms, while Kuron persists. This has been verified by analysis of test areas last summer, where no change in Kuron content was indicated two months after treatment. This longer persistence gives a longer and more continuous exposure of plants to the herbicide. Methods of Application In most of the work that has been reported to date, Kuron has been diluted at a ratio of 1-40 In the spray tank, and then this diluted spray has been applied to the surface of the water. This has been effective on both emergent and submergent species, however, presumably there are several other methods which might be used to apply Kuron,;.. Theses would include Injection beneath the water sur face, if feasible, and spraying over the surface with other dilutions that would be practical for various types of equipment. In any case, the main thing is to attempt to build up a lethal concentration in the water. 'There is no evidence that emergent speciet such as lily pads are controlled better if the surface is sprayed as compared with the injection below the surface. However, in many cases this would be the most feasible way to make the application. Methods of injecting the chemical directly into the water without pre-mixing are being investigated. -4- Toxicity Pish - There has been no significant fish kill in any of the reported field tests. Laboratory data indicates that if fish are exposed to Kuron at concentrations of seven or more parts per million, considerable mortality can occur. In field work where applications as h i g h as five parts per mil l i o n have been made, no evidence of f i s h kill has been seen. We feel that there is a reasonable margin cf safety based on the field experience to date. Conceivably, some f i s h could be. killed if trapped in areas of h i g h concentration. Some research workers have reported that fish caught in Kuron treated water were completely free of any flavor change, and as far as they w e r e concerned, there was no change in quality as a result of Kuron treatment. However, one report, and some laboratory findings, Indicate that Kuron treatment can affect fish quality. Therefore, more information Is needed before defi nite statements are made. On the basis of acute oral toxicity data, we do not expect Kuron, used in the suggested manner, to be harmful to livestock. Plankton Present evidence indicates that KUron does not effect pond plankton. However, this group of pond flora and fauna is suffi ciently complex and important that we should encourage more research on this aspect of Kuron use. OTHER HAZARDS CONNECTED WITH KORON USE Vegetation Stirrounding Ponds In two years -of experience in New Jersey,, no effects have been noted on trees or other vegetation growing on the banks of treated ponds. Therefore, there is reason for hope that we may not have a problem. However, it"Is important to realize that many of the places where TCUroo ultimately may be used will be on estates or other resort developments where vegetation around the pond border may be dense and valuable. We must consider injury to be a possi bility unti> we have more conclusive evidence that there is or is ' not a hazard. ^ -C-o-n-t-am-i-n-a-t-io'ney-o'-f--I-r-r-i-g-a-t-i-o-n-';-W-a-t-e-r Any time an herbicide is put into water that is ultimately going to be used on desirable plants, there is a possible hazardto plants that are sprayed or irrigated. We know- that if this concentration is applied to the more succulent, vegetable crops or to flowers, we can expect trouble, and in view cf the uncertainties DOW10 9 2 0 9 TO 16028 DOW1092093 ] DOW CONFIDENTIAL | of the situation, we would have to recommend that Kuron treated water should not be used for any irrigation or spraying purposes. Potable Reservoirs One of the aquatic weed problems in >;he east is in potable water reservoirs. Kuron can cause an off flavor in water, and we cannot recommend its use in this type of a situation. We hope that some of the water reservoir -people will evaluate this prob lem for themselves so ultimately the product could be cleared. Actually, they would want to do much of their own work regardless of what we do here,.and we will have to depend largely on them to make the decision. Suggestions for 1958 Use This is a new field for the Agricultural Chemical Department. We have some reason to believe that we have a winner (though an unprotected product), Thi3 new field may be fraught with hazards some of which, we have yet to recognize. We should not let our limited success so far lead us to become blind to these possible hazards, and our 1958 program has to be pursued cautiously. Kuron will not be recommended for aquatic weed control by The Dow Cneraical Company in 1958. The following suggestions are offered*; for those' conducting evaluations of the product. For control of such aquatic weeds as water milfoil, Myrlophyllum, fanwort, Cabomba; white water lily, Nymphaea, use one gallon of Kuron per acre foot of water (l.e., a pond one acre in surface area and one foot deep would require one gallon of KUron. If it averaged rive feet deep, it would require five gallons of Kuron). In addition: Treat small areas not entire lakes. Avoid bathing areas. Don't treat water used for watering livestock, irrigating or spraying crops or for human consumption. Avoid lakes with valuable shade trees or ocher plantings on the pond margins. Application can be made early in the growing season, after weed growth 1stwell underway, in any safe manner which will give uniform distribution over or under t&e water surface. This con centration will.not control most weeds in the potamogetn group, and other species may be.resistant. 1953 PROGRAM Agricultural Chemical Development A full scale development program on the product Kuron is planned for 1958. This will- be designed to get the following DOW1092094 -6- Information where feasible: (1) Spectrum of activity; (2) limitations in use; (3) addi tional Information on toxicity to adult fish, fingerlings, egg masses and plankton; (4) feasibility of injection type equipment; (5) general areas of utility; ( 5 ) best tine.for application; (7) persistence in the water; (8)- hazards of use; (9) possible effect on taste of water and/or fish and (10) duration of control. rnhe aquatic weed control field is a new one to Dow, and now that re have Kuron, we have a good opportunity of developing mere know-how in this field, making some sales, and laying the ground work for development and sales methods for new products which may be coming down the line. Kuron could well be Just a starter in this field. There are a number of possibilities In using 3ilvex in forms other than Kuron. These Include granular (acid or ester), amine salts, etc. We cannot overlook potential competition from related compounds such as 2 , U - D which Is now being sold (daringly) by another company. This competition may be expected to "flood" the research organizations with many types of related materials in 1958* We should watch the resulting experiments closely. In the meantime, we have a good record of field successes with Kuron which is a commercial product. We should agressively pursue Its development in 1958. We will, of course, do sufficient basic work on granulars so that we can move in that direction if' It. appears desirable later. 1742 Dov; Chemical Co. EPA Hearing Submissions Re: Cancellation - Volume 2 OflW1 15171S 16. "Petition for the Establishment of Tolerances for the Pesticide Chemical, (2,4,5-T) on Raw Agricultural Commodities", Sec. C: Full Reports of Investigations re: 2,4,5-T, 12/8/67* (1) Summary of 11 tests on safety of 2,4,5-T (A-K below) (2) Conclusion: -more data on 2,4,-D than 2,4,5-T is available, but indi cations are that two materials are comparable; acute oral toxicity of both in lab animals is in same range, 300- 1000 mg/kg. -long history of usefulness not produced evidence of unusual toxicity. A. "Acute Oral Toxicity of 2, 4,5-T to Rats, Mice, Guinea Pigs and Chicks", Rowe,. McCollister and Spencer, (D o w , 1950).1 (1) Single oral doses (administered by stomach tube) of 2,4, 5-T as a 10# suspension in olive oil, to mixed sex group of rats , mice and guinea pigs, 3% solution in olive oil given to chicks. 2( ) Symptons of poisoning = ataxia, myotonia; death at highest dosage levels; doses ranged from 0.1 - 1.0 grams/kg. (3) LD 50's: rats mice guinea pigs chicks 0.500 grams/kg. O .389 O.38I " " O.31O " (4) 2,4,5-T significantly more toxic to chicks than to rats. B. "Toxicity of 2.4-D and 2,4,5-T - a report on their acute and chronic toxicity in dogs", Drill and Hiratzka, 1953. ("There have been no reports concerning the toxic properties of 2,4,5-T"). (1) Experimental Procedures: adult mongrel dogs of both sexes 1 K 16029 1 used, fed "Fri ski es " ad lib, commercial 2,4-D and 2,4,5-T used. -single oral dose administered in capsules. Survivors autopsied after 14 days (acute studies). -*-- * -oral administration in capsules imbedded in 4-5 gram p i e c e ^ S of commercial canned dog food, 5 days/wk for 13 weeks a- (chronic studies). ^ 51719 (2) Results of Acute Studies : (a) 2,4-D; -400 mg/kg caused death in 2/2 dogs in 2-3 days fol lowing administration. -250 mg/kg - death in 3/3 in 4-8 days -100 mg/kg - 2/4 died in 9 days, 2 survived to 14th day - 25 mg/kg - no deaths, all 3 survived to day 14 (b) 2 , 4 ,5-%T: -400 mg/kg -1/1 died on day 2 -250 mg/kg -1/1 died on day 3 -100 mg/kg -1/4 died on day 7, 3survived to day 14 - 50 mg/kg -no deaths, all survived to day 14 (c) Oral for 2,4-D = approx. 100 mg/kg; for 2,4,5-T, = 100 mg/kg or higher (d) Body weight - decrease with larger doses of both 2,4-D and 2,4,5-f; these animals developed anorexia, those that died refused food towards end. (e) Symptoms : ataxia, stiffness in hind legs, myotonia 1GQ30 2 (f) Pathology: gastrointestinal changes - redness ofmuccsa in small intestine, some necrosis and inflammation, hepatic necrosis, mild renal tubular degeneration. Most deaths due to nonspecific changes - hepatic congestion, many cases of death due to pneumonia. (3) Results of Chronic Studies: (a) Mortality - -2,5,10 mg 2 , ^ - D or 2,il,5-T/kg: all dogs survived 90-day test period -20 mg/kg of compounds: all dogs died during study (b) Body Height - loss in weight occurred significantly only in those animals that died (c) Symptoms - survivors were free of any symptoms; in both 2,4-D and 2,^,5-T dead, weakness, leg stiffness, difficulty in swallowing food, bleeding from gums (d) Blood Count - only change observed = fall in % of lympho%cytes in 3 animals that died. (e) Organ Weights - no change in survivors; in 2 of 3 2, i-D deaths, slight increase in heart and kidney weight,, similar, change in 2 of H 2,4,5-T deaths. (f) Gross Pathology - 2,iJ-D`2 dogs showed areas of red ness in duodenum ; 2,^,5-T ' one dog showed diffusely reddened duodenum and jejunum, another demonstrated a generalized icterus. (g) Microscopic Changes - 5 cases of focal necrosis in the liver (not related to dosages nor death, thus, of no significance). Some duodenal hyperemia, some early infiltration of cells in the mucosa. Sub^ucosa aria serosa were normal. Slight increase in # of casts in kidney sections in some dogs (unrelated to dosages and of doubtful significance). 18031 3 ( ) Comment : I 151721 -effects of 2,4,5-T not as severe as those of 2 , ^ - D in acute studies. -delayed death in chronic studies with 2,*J-D may indicate a cumulative effect of 2,^-D. -signs observed in dying animals in acute study differed from those in chronic study. (5) Summary ; 2,4-D acute oral LD^Q in dogs = 100 mg/kg, doses at this level or higher produced a definite myotonia with anorexia and weight los s . 2,4,5-T acute oral in dogs = 100 mg/kg or higher; such doses produced only signs of a mild spasticity. Death during the repeated administration of 2,*1-D or 2,4, 5-T was not related to pathological changes in the liver, kidney, or other organs examined. C. "Summary of Toxicological Information on 2,JJ-D and 2,^,5-T Type Herbicides and an Evaluation of the Hazards to livestock associated with their use", (Rowe and Hymas, 195*0. (1) Early in 1950, Grigsby and Farwell published results of experiments with 2,4-D and 2,4,5-T involving domestic livestock, concluded "it seems that the farm use of these materials for pasture weed control is a reasonably safe p r o c e d u r e ." (2) Commercial Herbicides - formulations of active ingredients appearing as a salt Cwater-soluble) or an ester (soluble in oil); most formulations also contain a dispersant, a solvent, a wotting agent, perhaps a diluent (usually con sidered inert ingredients though they may affect herbicidal effectiveness). (3) Oral Administration of Single Doses : (a) test materials administered primarily by intubation. (b) aqueous, or olive oil or corn oil, solutions used 16032 n (c) LD50 's : 2,4,5-T 2,4-D flflH 151722 rats mice guinea pigs chicks dogs 500 mg/kg 389 mg/kg 381 mg/kg 310 mg/kg 100 mg/kg 375 mg/kg 368 mg/kg 469 mg/kg 541 mg/kg 100 mg/kg (d) toxic symptons of LD^0 ,s include loss of appetite, weight loss, depression, roughness of coat, general tenseness, muscular weakness; post mortem findings stomach irritation, minor liver and kidney injury, lung congestion. (4 ) Oral Administration of Repeated Doses -of 2,4 - D : (a) Rats - fed 2,4-D 5 times/week by intubation, in olive oil solutions. Dosages were 0.0, 3-0, 10.0, 30.0, 100.0, 300 mg/kg. Results - no adverse effects at control, 3, 10, 30 mg/kg `levels; 100 mg/kg group - gastrointestinal irritation, swelling in liver,- depressed growth rate; 300 mg/kg group failed .rapidly - died, severe gastro irritation observed. (b) Another Rat Study - fed 2,4-D for 113 days at levels of 0, 100, 300, 1000, 3000 and 10,000 ppm. Results - no adverse effects in control, 100 and 300 ppm groups; 1000 ppm group suffered depressed growth rate, excessive mortality, slightly increased liver weights, liver swelling; 3000 and 10,000 ppm groups were destroyed after 12 days since they wer^ not eating and were losing weight; examination revealed increased liver and kidney weight, 1. and k. patho logical changes. (c) Chicks - fed 2,4-D for 7 days at levels of 0,500, 1,000 and 3000 ppm. Results - only adverse effects in 3000 ppm group reduction in food intake and retarded growth rate (no histopathological exams made). 16033 5 DOW 1 1 5 1 7 2 3 (5) Oral Administration to Steers - (experiments performed to see if extrapolation of data on small animals to larger animals is justified). (a) "Esteron Brush Killer" used (formulation of esters of 27if-D~and-- administrations made by intubation. -experiment # 1 : 291 kg steer given single dose of 1000 mg/kg - no toxic symptoms. -experiment # 2 : 295 kg steer given 1000 mg/kg esteron for 3 days. results: general depression, decreased food and water intake, decreased rumen motility; animal died on 3rd day after last dose (death was undramatic). Necropsy revealed dry rumen contents with strong smell of esteron, abomasum was im pacted, intestinal contents entirely fluid, con gested mesenteric vessels, spleen dark and shrunken. -experiment # 3 ' 295 kg steer given 500 mg/kg for 2 days.t % results: on 3rd day, animal was off feed, rumen motility ceased. On 4th day, steer appeared perfectly normal, no discernible after-effects. -experiment # 4 ; 336 kg steer given 500 mg/kg for 3' days. results: no toxic symptoms observed, animal remained on full feed. -experiment # 5 : 250 kg steer given 100 mg/kg for 15 days. results: outward appearance normal. Killed 4b hrs after last dose for study. Duodenal hemorrhage, abomasum irritation, hemorrhagic necrosis of liver, fatty degeneration, slight edema- and congestion in kidneys were found. 16034 6 & lV I' (b) "Kuron" used In another experiment: 250 kg steer given 100 mg/kg Kuron for 15 days. results: outward appearance normal. Killed 18 hours after last dose for examination. Very slight edema in kidney, but this is frequently observed in untreated animals,* its significance is questionable. (6) Discussion: (a) Dogs more susceptible.to 2,4-D and 2,4,5-T than other species studied; chicks appear tolerant. (b) "Inert" ingredients in commercial formulations have no effect on toxicity of active materials. (c) 2,4-D and 2,4,5-T can be tolerated without adverse effects in doses only slightly smaller than those which cause toxic effects when given only once - these mater ials have a low degree of chronicity, therefore. (d) T h e m is a similarity in susceptibility of cattle and small% lab animals to these herbicides. (e) If esteron were applied at the normal rate of no more than J7 m g / s q . ft. (or 2 q t s . per acre) a 350 kg (770 lb.) animal would have to consume all forage on 7^4 s q . ft.to acquire a 100 mg/kg dose of herbicide, a level at which ill effects would not be expected. (f) ". . . there is little, if any, direct hazard to live stock or wild-life foraging areas treated with herbi cides of the type described herein. This has been con firmed by the extensive use of these materials over a number of years without any proved cases of adverse e f f e c t s ." (g) Spraying of certain plants with 2,^1--D can increase their nitrite content to hazardous levels, but some of these plants were sprayed accidentally, and others are not ordinarily eaten by livestock. Toxic amounts of these materials can be obtained if animals have access to spray tanks or other containers of the material. 16035 7 1 151724 151725 D. "Results of Toxicological Tests on (2,il,5-T)", D o w , August 1950. (data submitted to 1?DA Hearing on residue tolerances), C>i^ (1) Because of similarities between 2 Jl-D and 2,^,5-T, residue tolerances for both should be same - 20 ppm "would provide -- * a wide margin of safety." (2) 10/5 solution of 2,4,5-T in propylene glycol introduced into rabbit eye caused pain and irritation immediately, severe conjunctivitis and moderate corneal damage apparent 5 hours later, continued for 2 days before healing began. (3) 10 solution of 2,^,5-T in butyl carbitol acetate applied to rabbit ear and abdomen caused slight irritation. ( H) 2,4,5-T is moderate in acute oral toxicity for the four species, rat, mouse, cavie, and chick (rat more resistant, chick most susceptible). (5) Handling hazards and precautions: -swallowing, although unlikely, could cause serious ill effects; induce vomiting. -avoid contact with eyes and skin, d o n 't wear clothing or shoes contaminated with material. -no inhalation studies to date, but doubtful that toxic concentrations would be inhaled due to irritation it will produce in upper respiratory passages. E. "Toxicity tests in NuAmine D / T " , Report to Diamond Alkali Company by Hazleton labs, February 1962. (1) NuAmine D/T = 1,3 - propylene diamine esters of 2,^-D and 2,4,5-T. (2) Acute Oral Administration - NuAmine D/T given to SpragueDawley rats (6 groups of 5 each) by stomach tube, either in water emulsion or undiluted dosages of 10,31.6, 100, 316, 1000 or 3160 micrograms/kg body weight. Concentra tions of material varied from 1JS, 10$, or 1005Z. Observa tion period of 14 days following dosing. 8 (a) Mortality : After 24 hrs., 2 in 1000 microgram/kg X j y group, and all (5/5) in 3160 microgram/kg group died.'^ s On day 12, another in 1000 microgram group died, and another on day 14. These were only deaths recorded. (b) -O-t--h--e--r---E--f--f--e--c--t--s: ^ -10,31.6, and 100 micrograms /leg groups: n o r m a l ^ appearance and behavior, increase in body weight, noct pathological findings. - 316 micr o g ./kg : 4/5 seemed normal, 1 was depresse on days 12-14. Slight increase in average body weight. 2/5 showed congestio'h and hemorrhage of lungs. - 1000 mlcrog./kg: 4/5 normal at first, 1 showed depression, ataxia, and labored respiration after 4 hrs. 2 died after 24 hrs., survivors showed depression and labored respiration. After 48 hrs., all survivors appeared normal; at 2nd week, all showed unthriftiness, depression, labored respiration and ataxia. 2 more died on days 122:14. Autopsies showed lung,adrenal congestion, kidney e and stomach hemorrhage, hematuria, intestinal inflama- tilm, discoloration and/or reduced size in kidneys spleen and liver, stomach inflammation, congestion of fat around tests. - 3160 micrograms/kg: appeared normal following intubation; depression and ataxia after 1 hr.; pros tration, ptosis, salivation, labored respiration, poor reflexes after 4 hours; 1 death at 5 hours, survivors showed hematuria. Total mortality by 24 hours. Autopsies revealed congestion of lungs, adrenals, liver and spleen; kidney and stomach mucosa hemorrhage; intestinal inflammation; bloody fluid in stomach and urinary bladder. ( 3 ) Acute Eye Application - NuAmine D/T applied to eyes of 3 albino rabbius Cleft eye only, right served as control). 16(337 9 RJW 4 1 5 1 7 2 7 Single application of 0.05 ml of undiluted test material made into conjunctival sac. Periodic observations for 1 week. Pood (Purina rabbit pellets) and water ad l i b . (a) Results: Animals seemed normal throughout study, slight decrease in body weights in some. Eyes showed erythema, film over cornea, slight vas cularization of sclera and nictitating membrane, lacrimation, edema of lids (obscuring eye and preventing thorough exam after a few hours), exudation, corneal opacity, and corneal lesion (1 animal). (4) Acute Dermal Application' - albino rabbits used; single application of 5 0 1 volume/volume aqueous emulsion of NuAmine D/T at dose of 0.1 mg/kg body weight, and single application of undiluted test material at doses of 0.1, 0.5, 2.0 ml/kg. Test material applied to abdominal skin. "Purina Rabbit Pellets" and water ad'lib. (a) Results: 3 deaths at 2 ml/kg level, no deaths at any other level. Estimated acute dermal LD.5-0n of NuAmine D/T for albino rabbits = 1.2 ml/kg. 1. * 50% emulsion: a p p l i c a t i o n ^ .1 ml/kg) produced no signs of systemic toxicity, no pathological findings. 24 hours after application - moderate erythema and edema. At fourth and fifth days, erythema and edema subsided, but animals showed slight or moderate atonla and desquamation. By 12th day, almost all signs of irritation gone. 2. Undiluted: -0.1 ml/kg - normal appearance and behavior. Autopsy showed kidney congestion, mottled and blanched livers. -0.5 ml/kg - normal appearance and behavior. Autopsy showed kidney congestion, and granular appear ance of liver. c 16038 10 W lf 1 1 5 1 7 2 3 -2.0 ml/kg - 3 deaths at this level, on 4th, 5th, and 7th days of observation. 2*1 h r s . post application, 3 animals showed depression and labored respiration, 4th seemed normal. Toxic signs gradu ally became more severe: depressed reflexes and coordination, labored respiration, ptosis, ataxia, coma phonation, salivation. Autopsies showed con gestion or hemorrhage of lungs and kidney; bloody urine in 1 bladder, bright yellow urine in another; liver damage (blanching and discoloration) and toughened liver surface; spongy brain tissue with excessive fluid in skull; extremely congested or hemorrhagic appearance of skull cap and bone marrow. One survivor was sacrificed, showed congestion of kidneys. Subcutaneous edema, damage to all layers of the skin. Dermal' effects - 24 hrs. after application, ski.n at all dosage levels showed edema and blanched areas surrounded by moderate erythema. In 3 animals that died at highest dosage, derma], irritation was relatively unchanged at time of death. Survivors in all levels - edema subsided after 3-5 day:., scab formations or marked desquamation, atonia, %coriaceousness, and fissuring developed to end of observation. (5) Repeated Dermal Applications - albino rabbits given 1 ml/kg NuAmine D/T in varying strengths (4, 12, 20 oz./gal. aqueous emulsions) 5 days a week for 4 weeks. Results: each group showed moderate degree of dermal irritation - erythema, edema, atonia, desquamation. Several in 20 oz./gal. group showed fissuring. One animal in each of the test groups died, all showed systemic toxicity - depression, labored respiration, sprawling of limbs, weakness, weight loss. Moribund animals also showed prostration, poor coordination, depressed reflexes, clonic convulsions. Abnormal blood and/or urine findings in each group, severe liver, kidney and skin damage in 4 and 20 oz./gal. groups. E-l "Microscopic examination of bone marrow sections" from NuAmine D/T study, Hazleton Labs report to Diamond Alkali Co., 12/16/65- - supplement to report of 2/23/62; tests on bone marrow taken from rabbits receiving repeated dermal applications of NuAmlne-D/T. 18039 Results: No distinctive effect on bone marrow at 2 concentrations (4 and 12 oz./gal.). Higher con centration (20 oz./gal.) group showed somewhat atrophied adipose tissue. A possible effect - mega karyocytes (in 20 oz./gal. group) underwent degen erative changes, more so than in controls. P. "Results of 90-day Diet.-ry Feeding Studies of Dowanol 97B (ester of 2,4,5-T) in Rats", Dow, 11/27/61 (1) Dowanol 97B ester of 2,4,5-T is an agricultural herbicideo (amber liquid) (2) experimental procedure; 5 groups of 20 m & f rats were maintained for 90 days on diets containing O.O(control), 0.3, 0.1, 0.03, and 0.01$ of the ester. Food (ground Famo Laboratory Chow) and w a t e r ad_ l i b . (3) Results : 0.03 and 0.01% levels: no evidence of adverse effects; increase in average weight ,of spleen in males, Increase in body weight of females - believed due merely to chance. 0.3% level: growth retardation in males, liver and kidney/body weight ratio increased in males. M and F livers were large and light in color, some swelling and necrosis. Some swelling in male kidneys; female kidneys appeared greenish, some swelling and necrosis. Increase in serum alkaline-phosphatase determinations in males. 0.1% level: livers (m and f) showed some swelling and necrosis, females showed hypercellularity of glomerular tuft, swelling of renal tubular epithelium. Increase in average male kidney weight. Conclusions: the Dowanol 97B ester of 2,4-,5-T is moderate in repeated oral toxicity in 90 day feedings. Levels of 0 .03$ and below were tolerated without evidence of adverse effect. Male and female rats showed some injurious effects (liver & kidney pathology) at levels of 0.1$ and above. Long-term dietary studies (2 years, with rats and dogs) may be required if ester is found in significant amounts as residue in food. G. "The Toxicologic Effects of Certain Fungicides and Herbicides on Sheep and Cattle", Palmer and Radeleff, 1964 (1) "In contrast to insecticides, organic fungicides and herbi cides (with only a few exceptions) have generally been considered to provide comfortable margins of safety for grazing livestock when the compounds are used according to directions." 16040 12 (2) Sheep and cattle maintained on grain concentrates with hay supplements. (3) Commercially available formulations used, as fluid dilutions or in gelatin capsules; number of doses varies. Results: (1) Fungicides - a) "Captan" : sheep are regularly poisoned by doses of 250 mg./leg or higher; reduction to 50 or 100 mg/kg permits animals to eliminate most of material without being harmed. Cattle more tolerant of Captan than sheep. Depression and anorexia, tendency to stay away from group were only toxic signs in sheep; in one heifer, diarrhea and abortion observed. At necropsy, hepatic and renal changes noted but not remarkable. b) "Zineb11: Single doses of 500 mg/kg. tolerated by sheep and cattle. 90 daily doses of 100 or 250 mg./kg. did not poison sheep. In single poisoned sheep (15 doses of 500 mg./kg.), anorexia and bright yellow diarrhea observed. Necropsy showed congestion of the lungs, hepatitis, and nephritis. % c) "Ceresan M " : Sheep fed 1, 1.5, or 2 lbs. of treated grain per day. Lethal to all, at doses of 1 lb./day x 33 doses, 1.5 lb./day x 22 doses, or 2 lb./day x 6 doses. Signs of poisoning included anorexia, diarrhea, weight loss, nasal discharge, stilted gait and lameness. Necropsy showed .lesions characteristic for mercurial poisoning. (Ceresan contains mercury). (2) Herbicides - a) 2,4 - D : administered as alkanolamine salt and as propylene glycol butyl ether ester to sheep and cattle. Very little difference in toxicity of 2 derivatives. "Remark able tolerance" of 481 daily doses of 100 mg./kg. by sheep Indicates little probability of acute poisoning in normal applications of the compounds. Toxic signs in sheep - anorexia, depression, weight loss; in cattle muscular weakness, ataxia, dry, cracked muzzle, ulcera tion of nasal mucous membrane. Necropsy - lesions varied, usually liver and kidney degeneration;rumen stasis with bright, undigested inger-ta; hemorrhages in heart and excess of pericardial fluid. 13 151731 b) 2_j_, 5-T: administered as tricthylamine salt and as propylene glycol butyl ether ester to sheep and cattle. Salt appeared least toxic (sheep tolerated 48l doses of 100 mg./kg.) while esters were lethal at 369 doses of 100 ing./kg. Esters were lethal to sheep and cattle after 7 doses of 250 mg./kg. 2, l), 5-T somewhat moi'e toxic to sheep and cattle than 2, ^--D , "although poisoning under ordinary circumstances of use would be most unlikely." c) 2, 4, 5-TP (2 - (2, 4, 5-trichlorophenoxy) - propionic acid) administered as butyl ether esters of propionic acid derivative to sheep and cattle. Markedly more toxic than 2;^-D or 2, 4, 5-T (sheep succumbed to 11 doses of 100 mg./kg., cattle to 29 such doses). Signs of poisoning: anorexia .& progressive weight loss. Necropsy showed degeneration of liver and kidneys, hemorrhages on heart surface, congestion of visceral blood vessels, swelling of lymph glands, rumen atony with large quantities of lngesta. (3) Benzoic Acid Compounds - dimethylamine salts of 2, 3 , 6-trichloro- (Trysben) and 2-methoxy - 3j6-dichloro enzoic acids (Banvel D) tested. Both compounds slightly more toxic than phenoxyacetic acids studies. Trysben at dosage of 250 mg./kg. x 10 doses was lethal to the one sheep, but the cow was unaffected; at 500 mg./kg. x 2 doses, the compound produced mild poisoning in one other cow. Banvel D in doses of 250 mg./kg. x 10 doses did not affect a sheep, but killed another sheep at 500 mg./kg. x 2 doses. A cow was not affected by 5 doses of 250mg/kg. Signs of poisoning: salivation, trembling, depression, tympanites. Necropsy showed congested lungs, hemorrhages on heart, pericardium and larger blood vessels, undigested feed in rumen, edema in respiratory system, inflamed kidneys, liver engorged with blood. (*0 Trlazines - (Propazine, Simazine, and Atrazine) : admin istered to sheep and cattle; A trazine was lethal at all doses'tested (50 mg./kg. x 199 doses, 100 mg. x 1 6 , 250 x 2) for sheep, and lethal to the cow tested at 250 mg./kg. x 2 doses. At the 250 mg./kg. level in sheep, Simazine was more toxic than Propazine; at 50 mg./kg. Simazine was more toxic than Atrazine. Signs of poisoning (Propazine) anorexia and depression. Signs of poisoning (Atrazine and Simazine): muscular spasms and fasciculation, stiff gait, increased respiratory rates. Necropsy in sheep and cattle given Atrazine showed degeneration and dis coloration of the adrenal glands; congestion of lungs, liver and kidneys; presence of undigested food in rumens. 16042. (5) Miscellaneous compounds: a) Dalapon (2, 2-dichloropropionic acid) - sodium salt is of a low order of toxicity (500 mg./kg. x 10 doses not toxic to sheep or cattle, one sheep tolerated *j8l doses of 100 mg./kg.) No poisonous signs. __ ^ b) MCF Amine (2-methyl (4-chloro-o-toloxyacetic acid) - 1-- 4 alkanolamine salts poisoned one sheep lethally at ^ 383 doses of 100 mg./kg.; a cow was poisoned by 8 , doses of 500 mg./leg. but survived. Signs of poison- ^ ing in cattle: anorexia., chronic tympanites; in sheep, anorexia, depression and ataxia before death. c) Fenuron (3-phenol-l, "1-dimethyl urea) - appeared more toxiv. than most herbicides discussed, but high dosages still required to produce poisoning (e.g., 250-500 mg./kg. x 2-10 doses). Toxic signs: de pression, anorexia, complete incoordination (heifer abortion); slow recovery. Necropsy: lung congestion, heart hemorrhages. d) Bandane (polychlorodicyclo pentadiene isomers) - sheep poisoned by 3 doses of 250 mg./kg. but survived, while same dosage was lethal for cattle. Toxic-signs in sheep: salivation, anorexia, tympanites, dyspnea and depression. Toxic signs in cattle: tense muscles, muscular spasms. (Even when dosing stopped, signs progressed, duplicating tetanus). Death preceded by convulsions. Necropsy: hemorrhages of cerebrum and medulla oblongata, hemorrhage of right psoas muscle, skeletal fat replaced by gelatinous material, lung congestion. (6) Discussion: studies offer no "reason to alter the already generally accepted concept of the hazards pre sented by these herbicides." Further study needed . toxic signs. (7) Conclusions: feeding Ceresan M (13-38'mg./kg.) on treated grain by mistake can easily poison sheep; other materials studied are safe when used as recom mended . H. "Commercial Fishery Investigations", Philip A. Butler - Acute and Chronic Toxicity Studies, 1$641 (1) purpose of project: to learn how to protect and pre serve marine environment from possibly adverse effects of agricultural chemicals ; discovery of pesticides that may be useful In improving fish harvests 16043 15 fill 1 1 5 1 7 3 3 (2) "The need for this research does not imply that the widespread use of pesticide formulations automatically constitutes a serious threat to marine life." (3) "Even the most harmless of chemicals, including water, is toxic when present in sufficient quantity." (*0 different forms of marine life may react quite dif ferently to the same chemical (5) four bioassay groups (phytoplankton metabolism, oyster shell growth, shrimp survival, fish survival) tested for sensitivity to four pesticides (dyrene, methyl parathion, phosdrin, phosphamidon). Phosdrin and phosphamidon produced the least reaction; dyrene had some effect on all 4 groups, especially fish survival; shrimp survival was very sensitive to methyl parathion. (6) phytoplankton - microscopic sea plants, essential link in conversion of solar energy into food for more complex marine animals. Using decrease in growth, or decrease in carbon fixation as a standard, toxicities of pesticides may be compared. (7) Crustacea - shrimp is most valuable fishery; most pesticides kill terrestial members of shrimp's phylum .(arthropod) . Some pesticides paralyze shrimp and'other crustaceans, rather than kill; toxic cri teria for this group is effective concentration causing paralysis or death to half the samples within a stated period (EC^) (8) mollusks - clams and oysters store high concentrations of chemicals that exist in only trace amounts in the surrounding sea water. Mollusks, however, are able to close their valves and protect themselves from toxic substances in the environment. Thus, tests must be conducted at sublethal concentrations; growth is an objective index to measure, using EC,_q measure of effect. (9) fish.- younger specimens usually most quickly affected by pesticides. (10) 2, ^ , 5-T (polyglycol butyl ether ester): - ECrQ for oyster shell growth = 0.1^ mg./liter (96 h r s .), 1 v/e^k recovery period.I. I. "Commercial Fisheries Investigations," Philip A. Butler Laboratory Studies and Toxicology 16 (1) phytoplankton - majority of chemicals tested caused significant decrease in productivity at 1 ppm, al though at lower concentrations an increase in pro ductivity rate was frequently observed (probably because pesticide was toxic to animal part of natural phytoplankton community). Herbicides and DDT very toxic to some plant species. (2) Crustacea - post-larvae of brown shrimp and blue crabs are quite sensitive to chlorinated hydrocarbon insecticides. All shrimp and most crab tests con ducted in sea water with acetone stock solution of pesticide (constant flow systems, in which test solu tions are renewed continually, have advantage of in suring sufficient oxygen and desired concentration of pesticide). After,,exposure to lethal or near lethal concentrations, crabs and shrimps often mori bund for hours. (3) mollusks - oyster and clam tested, constant flow system with acetone-stock solutions of pesticides. Oyster closes its shell when sufficiently irritated by contaminated water - does not feed while closed and therefore does not grow; therefore relative chemical toxicity is indicated by changes in growth rate (shell growth). Controls used to compare growth rates. Chlor inated hydrocarbon insecticides were most toxic pesti cides to oysters - most inhibited shell growth at well beJow 1 ppm; other pesticides (erganophosphorus and carbamate insecticides) had little or no effect on oyster growth - they decomposed in water. Meta bolism increased at summer temperatures, therefore, at higher temperatures some chlorinated hydrocarbon insecticides killed oysters at concentrations which at lower winter temperatures only stopped growth. 1-- 4 week recovery period for reduced growth rate; data indicates that "a single field application which might temporarily affect oyster growth would probably not have a lasting effect." Chronic, rather than acute, exposure to pollutants is more likely. Chemicals tested included aldrin, dieldrin, DDT, toxaphene, malathion ond acetone (acetone used as a solvent in program, so tested for possible toxicity). In general, no decrease in growth rate; treated groups sometimes grew slightly better than controls. Oysters did not acquire tolerance to pesticides. -ECC(. for decrease in shell growth: J 2,4,5-T acid (temps, of 16, 30C) - no decrease at 2 ppm 2,4-D acid (temps: 9, 30C) - no decrease at 2 ppm 16045 (4) fish - juvenile white mullet & longnose killifish used as test animals in running sea water aquaria. 24 and 1)8 hr. median tolerated limit values (TLm) obtained. Chronic low-level pollution studies im portant, since many marine fish pass their early growth stages in estuaries. BOB 115173 3 groups of Spot (leiostoinus xanthurus) exposed 3 m o s . to sublethal concentrations of dieldrin (0.1, 0.01, 0.001 ppb), in running sea water. High mortalities, 3 0 - 3 1 % , but also in controls. No dif ferences in mean lengths, though some experimental fish had axial skeletal distortions, not in controls. Survivors exposed to 2 ppb dieldrin to determine if earlier low-level exposure had created any resistance: 802 of experimental fish survived 24-hr. exposure, while previously unexposed fish all died. cn -2, 4,5-T acid tested on longnose killifish showed, no effect at 50 ppm (24 and 48 h r s . TLm) with 19 C water temperature. -Esteron 99 (formulation): TLm for 50% mortality in mullet - 1.5 ppm (24 and 48 hrs.) at 20C; in killifish = 3-5 ppm (24 hrs.) and 3*0 ppm (48 hrs.) att 19C. % (5) Future considerations: "... to determine which pesticides now considered necessary may be expected to cause the least damage to marine resources. . . careful selection of the control agent and method of application can lessen the current pesticide hazards." J. "Commercial Fishery Investigations", P.A. Butler - Acute Toxicity, 19(>5 (1) Crustacea - shrimp - most valuable commercial fishery resource, spend part of life span in estuaries sus ceptible to pesticide pollution. Since they are rather closely related to insects, insecticides are particularly toxic to them - either kill quickly or paralyze them so they lose sense of balance. Tests conducted 24, 48 hrs. in flowing seawater. Results : 2;4,5-T acid had no effect on brown shrimp mortaxity or equilibrium at 1 ppm after 24, 48 hrs. (avg. water temp. = 28C) 2 , 4 .5-T polyglycol butyl ether ester tested on brown shrimp in 28C water caused 102 mortality (or loss of equilibrium) at 1 ppm after 24 hrs., and 202 mortality at 1 ppm after 48 hrs. 1-6046 18 Veon 245 tested on brown shrimp in 28C water had no efi'ect on mortality or equilibrium after 24 hr. and 48 hr. exposure at 1 ppm level. (2) Fish - younger specimens most quickly affected > therefore juveniles used in tests. Sea water used Results : -2,4,5-T polyglycol butyl ether ester tested ^ on Spot in lbC water temp.; had 24 and 48 hr ,y.. EC-0 of 0.32 ppm for mortality. CO -Veon 2 4 5 , also tested on Spot, in 27C, had Gt no effect after 24 and 48-hr. concentrations at 1 ppm. K. "Recommendations for Minimizing Dangers of Pest Control and Pesticides to Fish and Wildlife", John L. Georgq June, 1963 (1) be sure there is real need for pesticide use (2) discuss possible hazards with biologists prior to use (3) avoid treatment of any significant portion of range of a rare species or one with specialized habits consult with conservation officials % % (4) treat minimum necessary area; avoid direct treatment of streams, etc., consider danger of runoff contam ination (5) judge danger of chemical both by its toxicity and its disappearance rate (6) use method of application which will minimize contact with wildlife. Emulsions are more toxic to water environ ments than oil solutions or suspensions. Granules often concentrate the effect of the toxicant in one stratum. (7) no double-dosing (8) avoid main spring migration, nesting periods of birds, etc. when choosing time of treatment - consider possi bility of using repellants or scare devices to move mobile wildlife from area. (9) physical or biological control methods have advantage over chemical methods - more specific, reduce pests without loss of beneficial population. (10) susceptibility to different pesticides varies greatly among animals 19 (11) DDT susceptibility: 0.1 - 5 lbs./acre - U9K 1 1 5 1 7 3 7 ~ rn heavy kill effect on crustaceans and fish, moderate kill to amphibians and reptiles, some kill to birds, no effect on mammals until 5 lbs./acre level (12) table with toxicities of other chemicals as compared to DDT: 2,4,5-T derivatives (DDT=1): rats LD50 of 0.4 (single oral dose ) bobwhites - 0.2 chronic toxicity LD50 (10-100 day pheasants - 0.1 - II II LD 50 ft mallards 0.2 11 11 LD 50 II bluegilis - LD50 of 0.1 (96 hr. test ) (13) disposal of pesticides always difficult procedure unopened containers should be returned to wholesaler or sold) disposal of opened containers: - burned in a h o t flame (liquid organic chemicals) addition of lime (wettable powders) - dumping into sanitary landfill-type dump, contain erized if soluble - empty containers - burned or dumped - do not clean equipment at creeks or waterways 20 1 6 0 4 8  ''~-' ~>yz'r'--`r U.- ;.-;?'t'" :'. ' - : ^ iy.t'r~-::zi: ''' " .' OOW 1151350H ,< ) t J/Q . 0 9 ~ rV > - n - a 7 CLINICAL AND EXPERIilRNTAL INVESTIGATIONS CONCERNING THE .1 U ETIOLOGY OF CHLORACNE :3 can jhwss "by E.H. Schulz Arch.klih. exp. Derm. , 206 (1957) Pe- i i -"rlssl" -! (/ 569 - 596 PtStiCS?!- l . / O Eaifiia- A number of workers in a chemical factory at Hamburg developed certain dermatological symptoms between the middle of 1954 and spring 1955 -'iI. On the basis of anamneses and diagnoses, these symptoms were attributed 14I: to chloracne. Altogether 31 people were affected, whose individual clinical pictures will not be discussed in the present article. The clinical picture corresponded to that frequently obtained in occupations necessitating contact with perohlorinated naphthalenes and diphenyls. The symptoms comprised numerous comedones, pustules, some furuncles and retention cysts, all affecting invariably the face, neck, and the nape (see Fig. l), and in some cases also the back, chest, genitals, and the 16050 4F V m i 151351 2 In addition to dermatological symptoms, several patients presented chronic conjunctivitis- and blepharitis* General subjective com plaints, such as loss of appetite, debility,- and nausea were often . expressed* Fortunately, however, objectively detectable affections of the liver, kidneys, central nervous system, and the hemopoietio apparatus, were always absent. All the patients had worked in the 'Trichlorophenol Section' of the factory, manufacturing 2 ,4 ,5-trichlorophenoxyacetic acid, which is a widely.used, highly aotive herbicide, prepared from a-hexachloro* cyclohexane in a multistage process whose last two steps, being the most important ones in the present context, are as follows! ,1* Preparation of trichlorophenol by the alkaline hydrolysis of tetrachlorobenzene, carried out at 170C in the presence of sodium 'Tetrachloro benzene 2 ,4 5-trichloro phenol 2* Preparation of the final product by the addition of chloroacetio acid and sodium hydroxide to the trichlorophenol! 2 ,4 ,5-trichloro- 2,4,5-trichlorophenoxy- phenol acetio acid It was soon found that only those workers were affected who were engaged in the preparation and the furthor processing of trichloro phenol. 1 6 .0 5 1 I I E IS I14W It should, be mentioned In this connection that cases of chloracne have been found among personnel engaged in the manufacture of trichlorophenol in chemical works not only in Hamburg, but also in Southern and in Western Germany, these cases being occasionally accompanied by severe afflictions of the liver Trichlorophenol itself was first assumed to be the original oause of intoxication. According to previous reports^,' contact with highly chlorinated phenols, e.g. pentachlorophenol, causes chloracne This . assumption, however, soon had to be abandoned, for. the following two reasons* .... 1 Work with trichlorophenol had proceeded for two years without I. resulting in any harmful effect. The complaints first arose after a change in the preparation of trichlorophenol, whose details can no longer be neglected. ; ; ; >* - 2 The results of the animal experiments clearly disprove the causative function of pure 2 ,4 ,5-triahlorophenol. - Animal experiments The animal experiments were carried out on rabbits' ears, on which HU- J.U1CU~1A_A O_ A_AJU *ATl C- _u_u_o_iw4 , Braun , and Landes and ethers used highly chlori nated naphthalenes and induced symptoms very similar to those of chlor acne In human subjects. In each animal, the inside of one ear was painted daily with the substances to be tested for their chloracne-inducing activity, whilst the other ear, serving as a control, was treated with the solvent only. The duration of the experiments varied between 3 and 8 weeks. The chemical plant mentioned above supplied the technical 2,4,5-trichlorophenol (95^ pure), which was employed in 25# and 5# solutions in polyglycol and resulted in the following symptoms* inflammation of the , ears, accompanied by the reddening of the surface and moderate swelling, 161/52 developed in about 5 to 7 daysj a few days later the picture changed the diffuse inflammation had subsided and new symptoms appeared, which closely resembled those of chloracne in man. Follicles,filled with hyperkeratotic material, projected out of the plane of the skin, so C9 that the surface of the latter assumed a sandpapery appearance (see S S Fig. 2). In contrast, ears treated with the solvent alone developeaa no symptoms, ` ; vV:\, d. Fig, 2 - 03 d 03 Babbit's ear afte a 3-week treatment with a li solution of tech nical txichlorophenol in polyglycol (follicular hyperkeratosis, follicular distension) ' From the histological point of view, an acanthotic thickening of the epidermis was observed, together with edema and moderateoell infil tration in the cutis. The follicles were strong and their epithelia, distended almost infundibularly and filled with keratotic material, were extended. Dnlike technical trichlorophenol, chemically pure, twice-distilled trichlorophenol did not induce these symptoms even after an 8-week application. Experiments using the distillation residua gave once more the some pooitive results. The results are shown in Table 1 iaiowc: O Table 1 . Results of animal experiments carried out with a view to determining the . etiology of chloracne (by painting rabbits' ears) cn CO. cn Substance 2 ,4 ,5-Trichlorophenol (technical grade) 2 ,4 ,5-Trichlorophenol (chemically pure) 1 2 ,4,5-Tetrachlorobenzene * `. '> Distillation residue o f trio h lo ro p h e n o l Structural formula Concentration * R esults Hepatic Ear toxicity oh . 5 + + slight OH CI : c i-y 'V -c i 5-10 5-10 / / m 1-5 + + slight - None It emerges from these results that the substance causing chloracne is not trichlorophenol itself, but arises in all probability as a by product in the alkaline hydrolysis of tetrachlorobenzene into trichloro phenol Further investigations aimed at gaining more information of the nature of the substances causing chloracne. Since, owing to extraneous circum stances, the residue could not bo separated, synthetic compounds were used in these experiments. Naturally, such compounds were selected that were likely to be formed in the industrial production of trichloro phenol from totrachlorobenzeno. The results are listed in Table 2. , * Carried out in collaboration with Nr. Sorge, Hoad of tho Trichloro- phenol Section. 16054 Table g; Eesults of animal experiments carried out with a view to deter mining the etiology of chloracne (by painting rabbits' ears) CJl (-* cocn on Substance Structural formula Diphenyl ether 0~0 Mono- , di-, tri-, a and tetrachlorin- X ated diphenyl - .V ethers ~ a" X V Concerntration * 5-10 5-10 Results Ear Hepatic Remarks toxicity /J slight Diphenylene oxide (dibenzofuran) O ^q ; Monochlorinated dibenzofuran j' X( ^ ) 5-io 5-10 Tri- and tetra ohlorinated di benzofuran / b * none b.l-5 b/ / /PositiaE Iof the very s Cl atoms <+) strong 1are un certain Experiments with diphenyl ethers showed that neither the unsubstituted nor any of the mono-, tri- , and tetrachlorinated ethers was capable of pro ducing symptoms of chloracne in the rabbits' ears* Since, their formation under the relevant reaction conditions is possible, tho chlorino derivatives of dibenzofuran (diphenylene oxide) were next tested. Dibenzofuran differs from diphenyl ether in the presence of a furan structure by ring closure tdcing place between two benzene rings. . Tho unsubstituted and the monochlorinated compounds were found to be Translator's noto Dio. Dichlorodiphenyl ether is omitted. 16055 51356 inactive in the animal experiments. The tri- and the tetrachlori- nated dibenzofurana, on the other hand, exhibited a strong hepatic toxicity. Daily painting of the ears (over an area having a diameter of about 3 cm) with 0 .1 and 0 .5$ solutions led to death in 2 to 3 weeks. Autopsy revealed an appreciable engorgement of the liver and distended necrotic tissues, occasionally imbibed through hemorrhages. A single peroral application of a doge of 1 -led to severe hepatic conditions, which could be studied with the aid of the Hofmann 5 Oettel modification of the bromosulfthalein reaction. The symptoms described above appeared also on the ears of. the animals, but to a smaller extent, as in the experiments with the distillation residue. Therefore the question still remains whether tri- and tetrachlorinated dibenzofurans were the true cause of the cases of chloracne under 'consideration. _ .* Although the question may be posed whether the hi&ly chlorinated naphthalenes and diphenyls, whose chloracne-inducing activity has long been known, could be regarded as the cause in the present case as well, from a chemical viewpoint it is hardly probable that these compounds can be formed under the reaction conditions in question. ` Clinical observation led a step nearer to elucidating the nature of the cause. A chemical laboratory assistant ha3 recently developed severe chloracne. This patient had been engaged in the laboratory preparation of highly chlorinated diphenylene dioxides in a laboratory outside Hamburg, where, after about 10-14 days, he developed chloracne in con junction with facial dermatitis. Since the patient worked with chemically pure compounds, it must be assumed that highly chlorinated diphenylene dioxides axe capable of evoking symptoms of chloracne in man. a a a l-ci Tetrachlorodiphenylena dioxide (positions of the Cl atoms ar9 uncertain) These oompounds may have a causative function in tho chloracne cases |i2etsT I found in the chemioal plant as well, since, from a chemical view- SS point, chlorinated diphenylene dioxides may be formed in the hydrol of tetrachlorobenzene into trichloropheriol. .r Animal experiments with chlorinated diphenylene dioxides are in pro gress, and the results obtained so far indicate that tetrachlorodiph lene dioxide has a high hepatic toxicity in rabbits. Although the proof is still incomplete and the distillation residue of the technical trichlorophenol has not been investigated, it is hoped that a contribution has been made to the etiology of chloracne, parti cularly with the aid of the highly chlorinated diphenylene dioxides. Further investigations are aimed at the final elucidation of this problem. ' : ',,.'y.'. V'" ' ; ' Discussion 4. A. Szakall (Hamburg)t Comedones on the zygomatio arch of patients wearing speotaoles are "probably ascribable to the chafing of the surface "cells of the horny layer, followed by cell proliferation with increased horny formation. The inner41 surface of the spectacle frame in contaot with the skin becomes rough in use, and gives rise to friction. Pinkus J. invest, derm., 2 , 431 (1952)J7 has shown that a weakening, of the horny layer leads to cell proliferation, with increased horn formation. The removal of four surface cell-layers is sufficient to result in cell proliferation, .; P. Keller (Aix-la-Chapelle)x Is it possible that the formation of large comedones around the eyes in patients wearing spectacles is due to a chlorine content of the synthetic material of the frame ? These comedones were found in a tank officer around that eye only, which he used with the periscope, and the formation of the comedones persisted for years afterwards. *. Translator's notci Sic. 18057 i -< t vr; - -:i| > . jc=- ' 7c 't 'xj; <V if '( .I `I j I Jl \ \ >f1- ij|l:r i DOW1 1 5 1 3 5 8 9 0 Braun-Fnlco (llainz) j With respect to Prof, Keller's renarks concerning the follicular 'spectacles hyperkeratosis', this .is believed to have a physical cause (e.g. the pressure of the frane), and resenbles in this, connection the comedones appearing after x-rs; contact irradiation* .. : References! .... ;' 1* E.W. Baader and H*J. Bauer, Industrial intoxication due to~ pentachlorophenol* Industr.- Med. a* Surg. 20, 286-290 (1951). 2* W. Braun, Chlorakne, Monographien zur Zeitschrift Berufsderaatosen (Chloracne, Monographs of the Journal of Occupational Dermatosis) vol. 1* Aulendorf: printed by Editio Cantor. i. . . . 3* H. Grimmer, Occupational acne caused by chlorinated aromatic hydro carbons, Zbl. Arbeitsmed. u. Arbeitsschutz, 76-33 (1955) 4c E* Th* Hofmann, and W* Neumann, Animal experimental investigations of the dermatological effect of chlorinated naphthalenes, Zbl* Arbeitsmed. u. Arbeitsschutz _2, 169-173 (1952). 3. E.Th* Hofmann, and H. Oettel, The use of the bromosulfthalein . reaotion as a simple micromethod in the study of the hepatio function,Arztl, Wschr. 1954. 965-967 . . 6* E. Landes, Discussion, Bemerk. Dermat. Wschr. 150. 1191 (1954). -y'.*`...*~.**;,-i*. O . ./* " :.7 r If "i; j'*? gcetsUMlJO : Uf. O ~ a 13- 11-37 CLINICAL AITO BPERIWF3TAL INVESTIGATIONS CONCERNING THS ETIOLOGY OF CHLORACNE by E.H. Schulz Arch.klih. exp. Perm., 2 0 6 (1957) i / 589 - 596 Paso J L fetta?) I./ Esito A number of workers in a chemical factory at Hamburg developed certain dermatological symptoms between the middle of 1954 and spring 1955 On the basis of anamneses and diagnoses, these symptoms were attributed to chloracne. Altogether 31 people were affected, whose individual clinical pictures will not be discussed in the present article. The 'clinical picture corresponded to that frequently obtained in occupations necessitating contaot with perohlorinated naphthalenes and diphenyls. The symptoms comprised numerous comedones, pustules, some furuncles and retention cysts, all affecting invariably the face, neck, and the nape (see Fig. l) , vand in some cases also the back, chest, genitals, and the limbs, ' - , Fig. 1: Chloracne arising from contact with technical trichlorophenol (chemical worker, aged. 35) J- FQ 9/7 16059  . . ' .^;;v _ .; . . 2 In addition to dermatological symptoms, several patients presented chronic conjunctivitis- and blepharitis. General subjective com plaints , such as loss of appetite, debility,'and nausea were often expressed. Fortunately, however, objectively detectable affection of the liver, kidneys, central nervous system, and the hemopoietio apparatus, were always absent. All the patents had worked in the 'Trichlorophenol Section1 of the factory, manufacturing 2,4,5-trichlorophenoxyacetic acid, which is a widely used, highly active herbicide, prepared from a-hexachlorocyclohexone in a multistage process whose last two steps, being the most important ones in the present context, are as followsi ,1. Preparation of trichlorophenol by the alkaline hydrolysis of tetrachlorobenzene, carried out at 170C in the presence of sodium hydroxide end aethanolt .* Tetrachloro benzene , 2 ,4,5-trichloro- phenol 2. Preparation of the final product by the addition of chioroacetio acid and sodium hydroxide to the trichlorophenol* : ; 2 ,4,5-trichloro- phenol 2 ,4,5-trichlorophenoxyacetic acid Xt was soon found that only those workers were affeoted who were engaged in the preparation and the further processing of trichloro phenol. 1 T: It should, be mentioned in this connection that cases of chloracne have been found among personnel engaged in the manufacture of tri- chlorophenol in chemical works not only in Hamburg, but also in Southern and in Western Germany, these cases being occasionally accompanied by severe afflictions of the liver, . '. Trichlorophenol Itself was first assumed to he the original oause of intoxication. According to previous reports^-,' contact with highly chlorinated phenols, e.g. pentacblorophenol, causes chloracne. This . .assumption, however, soon had to be abandoned, for the following two reasons: ; - * *- 1, Work with trichlorophenol had proceeded for two years without resulting in any harmful effect. The complaints first arose after a change in the preparation of trichlorophenol, whose-details can no longer be neglected. !-v- . %^ '* 2, The results of the animal experiments clearly disprove the causative funotion of pure 2 ,45-triohlorophenol. - Animal experiments ;.V.. The animal experiments were carried out on rabbits' ears, on which H U- Xi*U-lC..U.i~.U OMUj i1tI6. .U,M ,OU 4, 74 f ,,_- _--_----2 f nd Landes'_6' and others CL rrVOwv nated naphthalenes and induced symptoms very similar to those of chlor acne in human subjects. In each animal, the inside of one ear was painted daily with the substances to be tested for their chloracne-inducing activity, whilst the other ear, serving as a control, was treated with the solvent only. The duration of the experiments varied between 3 and 8 weeks. The chemical plant mentioned above supplied the technical 2,4,5-trichlorophenol (957* pure) , which was employed in 2# and 57^ solutions in polyglycol and resulted in the following symptoms* inflammation of the , .j.ears, accompanied by the reddening of tho surface and moderate swelling, / tJ&i developed in about 5 to 7 daysf a few days later the picture changed - the diffuse inflammation had subsided and new symptoms appeared, which closely resembled those of chloracne in man. Follicles, filled with _ hyperkeratotic material, projected out of the plane of the skin, so G ! that the surface of the latter assumed a sandpapery appearance (see Fig. 2). In contrast, ears treated with the solvent alone develope^-- t cn ; .H -co ' :''CT5 CO From the histological point of view, an acanthotic thickening of the epidermis was observed, together with edema and moderate, oell infil tration in the cutis. The follicles were strong and their epithelia, distended almost infundibularly and filled with keratotic material, were extended. Unlike technical trichlorophenol, chemically pure, twice-distilled trichlorophcnol did not induce these symptoms even after an 8-week application. Experiments using the distillation residue gave once more the same positive results. Tho results are shown in Table 1 below.  -1 ' * :ni*l .f I " -lIi .-|it I i :| i i J. .1 ;l DOW1.151303 i 5 Table 1. Results of animal experiments carried out with a view to determining the . etiology of chloracne (by painting rabbits* ears) Substance Structural formula Concentration * R esults Hepatic Ear toxicity 2 ,4,5-Trichlorophenol (technical grade) 2,4,5-Trichlorophenol o h * -:' .* .4 vrl i J " OH * V !-- 5 ++ slight (chemically pure) 5-10 1 2,4,5-Tetrachloro- benzene . ta ::: cCli--- W - c Cil 5-10 > Distillation residue of triohlorophenol 1-5 ++ slight /i " None It emerges from these results that the substance causing chloracne is not trichlorophenol itself, but arises in all probability as a by product in the alkaline hydrolysis of tetrachlorobenzene into trichloro phenol, * Further investigations aimed at gaining more information of the nature of the substances causing chloracne. Since, owing to extraneous circum stances, the residue could not bo separated, synthetic conpounde were used in these experiments. Naturally, such compounds were selected that were likely to be formed in the industrial production of trichloro phenol from totrnchlorobenzeno. The results are listed in Table 2. * Carried out in collaboration with Dr Sorge, Read of the Trichloro- phenol Seotion. 16063 Table 2: Eesults of animal experiments carried out with a view to deter mining the etiology of chloxacne (by painting rabbits' ears) cn GO cn> Substance Structural formula Concentration * Diphenyl ether ,0^0; Mono-, di-, tri-, a a - and tetrachlorin ated diphenyl ethers -- 5-10 5-10 Results Ear Hepatic Remarks toxicity i/ . slight Diphenylene oxide (dibenzofuran) .0^0.. / Monochlorinated dibenzofuran 5-10 5-10 Tri- and tetra ohlorinated di benzofuran h m none b.i-5 f/ V jPositiar Iof the very sCl atoms (+) strong Iare un certain Experiments with diphenyl ethers showed that neither the unsubstituted nor any of the mono- tri- and tetrachlorinated ethers was capable of pro ducing symptoms of chloracne in the rabbits' ears. Since, their formation under the relevant reaction conditions is possible, tho chlorine derivatives of dibenzofuran (diphenylene oxide) wore next tested, Dibenzofuran differs from diphenyl ether in the presence of a furan structure by ring clooure talcing place between two benzene rings, . The unsubstituted and the monochlorinated compounds were found to bo * Tronolator'a note 3io. Dichlorodiphenyl ether is omitted. nyjr, G9GTST inactive in the aniaal experiments* The tri- and the tetrachlorinated dibenzofurar.s, on the other hand, exhibited a strong bepatic toxicity. Daily painting of the ears (over an area having a diameter of about 3 cm) "with 0.1 and 0.5/ solutions led to death in 2 to 3 weeks. Autopsy revealed an appreciable engorgement of the liver and distended necrotic tissues, occasionally imbibed through hemorrhages. A single peroral application of a doge qf 1 fflg/iSg led to seYere hepatic conditions, which could be studied with the aid of the HofmannOettel^ modification of the bromooulfthalein reaction. The symptoms described above appeared also on the ears of. the animals, but to a smaller extent, as in the experiments with the distillation residue. Therefore the question still remains whether tri- and tetrachlorinated dibenzofurans were the true cause of the cases of chloracne under 'consideration. Although the. question may be posed whether the highly chlorinated naphthalenes and diphenyls, whose chloracne-inducing activity has long been known, could be regarded as the cause in the present case as well, from a chemical viewpoint it is hardly probable that these compounds can be formed under the reaotlon conditions in question. Clinical observation led a step nearer to elucidating the nature of the 'cause. A chemical laboratory assistant has recently developed severe chloracne. This patient had been engaged in the laboratory preparation of highly chlorinated diphenylene dioxides in a laboratory outside Hamburg, where, after about 10-14 days, he developed chloracne in con junction with facial dermatitis. Since the patient worked with chemically pure compounds, it must be assumed that highly chlorinated diphenylene dioxides are capable of evoking symptoms of chloracne in man. aa Tetrachlorodiphenylene dioxide (positions of tho Cl atoms are uncertain) These compounds nay have a causative function in tho chloracno cases found in the chemioal plant as wall, since, iron a chemical view point, chlorinated diphenylene dioxides may be formed in the bydrolyi&As of tetrachloroben'zeno into trichloropheriol. . " ^ . ' :. CO C73 Animal experiments with chlorinated diphenylene dioxides are in pro-^j^ gress, and the results obtained so far indicate that tetracblorodipheny- lene dioxide has a high hepatic toxicity in rabbits. Although the proof is still incomplete and the distillation residue of the technical trichlorophcnol has not been investigated, it is hoped that a contribution has been made to the etiology of chloracne, parti cularly with the aid of the highly chlorinated diphenylene dioxides. Further investigations are aimed at the final elucidation of this ' problem. Discussion . ' L.:# :' " v ` J..' \'r' A. Szakall (Hamburg)x Comedones on the zygomatic arch of patients wearing speotacles are 'probably ascribable to the chafing of the surface 'cells of the horny layer, followed by cell proliferation with increased horny formation. The inner surface of the spectacle frame in contaot with the skin becomes rough in use, and gives rise to friction. Pinku3 /~J. invest, derm., l^f 431 (1952)_7 has shown that a weakening, of the horny layer leads to cell proliferation, with increased horn formation. The removal of four surface cell-layers is sufficient to result in cell proliferation. P. Keller (Aix-la--Chapollo)x Ig -t possible that the formation of large comedones around the eyes in patients wearing spectacles is due to a chlorine content of the synthetic material of the frame *1 These comedones were found in a tank officer around that eye only, which he used with the periscope, and the formation of the comedones persisted for years afterwards. Translator's note: Sio. 16068 151367 0. Braun-Falco (Mainz) i With respect to Prof Keller's remarks s concerning the follicular 'spectacles hyperkeratosis', this.is believed to have a physical cause (e.g. the pressure of the frame), and resembles in this connection the comedones appearing after x-ray contact irradiation .v References: 1 E.W. Baader and HJ. Bauer, Industrial Intoxication due to' pentachlorophenol Industr.--Med. a Surg. 20, 286-290 (1951). 2 W. Braun, Chlorakne, Monographien zur Zeitschrift Berufsdersatosen (Chloracne, Monographs of the Journal of Occupational Dermatosis) vol 1 Aulendorf: printed by Editio Cantor. l. , ' 3* H. Grimmer, Occupational acne caused by chlorinated aromatic hydro carbons, Zbl. Arbeitsmed. u. Arbeitsschutz, Jj, 76-83 (1955) 4 E, Th. Hofmann, and W. Newmann, Animal experimental investigations of the^dermatological effect of chlorinated naphthalenes, Zbl. Arbeitsmed. u. Arbeitsschutz 2 , 169-173 (1952). 5 H.Th. Hofmann, and E. Oettel, The use of the bromosulfthalein reaotion as a simple micromethod in the study of the hepatio function,Arztl. Wschr. 1954. 965-967. `r 6 E. Landes, Discussion, Bemerk. Dermat. Wschr 130. 1191 (1954). : w ^ Cl m * n Ah 0 , I f.s M - s u O w y w 'i / - 1151368 .. ? - C f] 7 3 -11-37 .,.I lifizicrlin Etinop)icn-Tt ; !j K. H. Scnuu: Untcrsiicluiiigiiu zur tiologie der Clilonn-nc 6S9 !i. *t negativ, dium ist. n-vli >i;Ji inti4fsduegnnidk"slaetaisroBntis.etEdluwaimnroadhnnlluengsrccca--hiit.iuiviiM.ie:vir;, .; einer sekundren, duu i, i Fnnktions-itrimg dir A [sprechen. Ohne Tic-rti. k- s negativen Ausfalls de I , i - : Durchschnitt wesentlich hher als hei der Psoriasis, doch nur wenig ber Jeu Werten des konstitutionellen Ekzems lagen. Besonders au'llig und ..ji.iTNdaecrhpPremfupnhgigauusf b(1re4itFerlelre)BatsriostzweLrtcseornscdheresinthomhierrdiDe uFrecshtssctehlnluitntsg-, r.iidnophilic nur zu */7, die Derm atitis herpetifonnis (12 Flle) dagegen fast in der H lfte der Flle negative Thom-Tcsto hatte. Das Verhallen de Pemphigus ist um so bemerkenswerter, als es sich ja bei ihm um eine schwere Erkrankung handelt und auerdem sehr hohe AGTH- b/.w. Cortison-Dosen nugewendet werden .knnen, ohne da, wie hei anderen b,cj i g m it besonders filierer Zuverlssigkeit uu>t- ); * Dermatosen, auf eine derartig forcierte Hormontherapie verstrkte Rckflle folgen. Ich fasse zusammen: Ein negativer Ausfall des Thorn-Tests braucht durchaus nicht Ausdruck einer primren oder sekundren Rindcn- *? il pro sehr die erh 10 Tage eblichen lAanhg- FIfuilnfcktdioens spstcrrournaglcznu Cseoirnt.isEonr -bTeedsatsr,f aduefr jedbeenr Fdaiell Adenrs"prcbcehrpbrarfkucnigt mdeirt lieb jedoch dabei crlul- Peripherie Auskunft gibt. Die intravense Modifikation des Eosinophilen- c sich der Thom-To-t * dagegen die il, (fgl. e>--S C E ortbonDepot- Tests nach Tkorx ist ein zuverlssiges, auch in grerem Umfange an wendbares und daher empicldcnswertos Verfahren. Es ergab sich, da im dermatologischen Krankengut der Thorn-Tcst relativ oft negativ aus dculung.skveise zu einer r r i Leistung des Rinden- i niid'itnl ci usnioenl lec uBn de esicnhtrwacchh- gelten sollte, nfilclht tunoddedriedoHchhenidcehrt Eaollseiinnopdhaiflenr -mAuasggaenbgesnwd eirstte. aDlleemr sAicnhscahuesindnieaseehr Feststellung ergebende Fragenkomplex bedarf . weiterer eingehender Bearbeitung. n Thorakal- bzw. im I u einem inehr oder niorn-Werte. ] > sei in CS. IC. IT. Schulz-H am burg: Klinische und cxporinm dcllc U tiler- . S`v;ivtiiiiin u. llonv* Hichungcn zur tiologie der Chlnraciie. Mit 2 Textabbildungen. hincren ihrer I*.it ii-sinhntcr-Kr.-'cliciiunr.vn In einem Hamburger chemischen Work traten in der Zeit von Mitto 1054 bis Frhjahr lik>5 bei einer Anzahl von Arbeitern Haiitvcrndcriin- I rin negatives En:cbn die Zuvi-rl.'-ivki ii nl, nie lirkuuni i-r. im i-rlih.-'.ikeir auf ACTfl -'rn auf, die nach Anamnese und Befund als sogenannte C'liliaacne mzusprechen waren. Insgesamt .waren .11 Personen erkrankt. Auf das klinische Bild soll hier nicht im einzelnen oingcgangenw erden. Es ent sprach weitgehend den nach beruilichem JCuntuki mit perc!iimi<`itfu X ,.|.bk.dinen lind Dii-licnrlcn hufiger beobachteten ICrankiiciisbiMcn:. Die I .thi'e.-rv Kiint.i-ncrkelirriTt-c-d-tici!'i.T Mi.-Iiiinven e&r l'-gi:-.;'. unbci lieh.'ieliti'jl. * i ui (Id Falle) fiel d -r ui (07 Flle) sogar -'i; Anette hier zwar im hrseheinungen setzten sielt au zahlreichen Comodi-ncn, Pusteln, fiiivti'lRJ*> Furunkeln und ib-ientionsevsten 'zusammen und cr.siieckten sielt ruueailiiiRTiPckaielnc,uBaruufatG, eGsiecnhitt,alHieanlss,oNwaieckdeien.EBxetiremmeihtreterennbKefraallnekne(nAwitabr.el)n. Neben den Vernderungen der Haut wiesen mehrere Patienten 'Rhurioidn.ies.esleihcwCerodnejnu.uwcliicvAiiipdfeAitiitulnndsigBkliedpt,hMaraitttiidgekneiat.uUf.br.lSkuebitjewktairveen Amlclghcr-elt zu eruieren. Objektiv nachweisbare Schdigungen von Leber, t>irX 'H 16068 U H IV V W W '< * 500 K. H. SciruLz: : i\-r * j.` V.4 ;*..rs iS '-V3 ;1 Uieren, Zentralnervensystem und des blutbildenden Apparates wurdtu erfreulicherweise aber in keinem Falle festgcstellt. Die K ranken arbeiteten alle im sogenannten Trichlorphcnolbetriob iles W erkes, in dom ein viel verwendetes, hochwirksames Unkrnutver- tilgungsm ittel, die Triehlorphcnoxyessigsure, hergestellt wurde. Der Herstellungsgang dieses Produktes geht vonm a-Hexachlorcyclohexan aus und durchluft m ehrere Stufen. Die beiden letzten, fr uns wichtig, aten rhasen sind: . 1. die H erstellung von Trichlorphenol durch alkalische Verseifung von Tetrachlorbcnzol bei Tem peraturen von 170C in Gegenwart, von Xation- lauco und M ethanol CI OH eine im <ier Hcrsich die 2.D: urschlic H"4, .-GH -- !1 i .ii r 01 ++ XCah,OOHH / H l : t" * CD ci * i .I :i Tetrachlorbcnzol 2, 4, 5-Trichlorphenol und 2. die Gewinnung des Endproduktes aus Trichlorphcuol unter Zugabe von Monochloressigsure und Xatronlauge: OCH.COOH ti + CI CH, COOII -t- X OH l'^l-- CI CI-- 1 ) 2,4, 5 Trichlorphcnol t. 2, 4, 5-Tricldorphenoxycssigsure Es zeigte sich nun bald, da nur diejenigen A rbeiter erkrankt waren, n die bei der Herstellung und W eiterverarbeitung des Trichlorphcnois be schftigt waren. An dieser Stehe sei erwhnt, da auch in chemischen Fabriken auer halb H am burgs in Sd- und U V -tdcuts'-hlnud bei d er G ew innung vm AM,. 1. CIi 4 :J Trichlorphcnnl Erkrankungen an Chlnracnc, die zum Teil m it schweren Leber.sehilen koinbiiu-.M t waren, aufgol relen sind. Unsere Vermutung giui; zuneh-t dahin. da das TricJiorpbcnol selbst die urschliche Xoxe darslellt, zumal in der L iteratur MittcihuiL'vu existieren, wonach der Umgang mit hoher chlorierten Phenolen, z. H. Pent.ieliloiple-nul. zu Ei kritkungcu au Chloracnc g efhrt htte (D aa ujik u . a c k i: u. a.j. Diese Annahme m uten wir ab er bald fallen lassen, und zwar aus furzenden Grnden: 1. Mit Triehlurpbenol war schon etw a 2 Jah re lang g earb eitet wurden, Zu d nir.chen irsihclil'lenen c! iues 0; -cclicn! mir mit ohne da Gesundheit'Schden beubachtct worden waren. E rst nachdem Wiivlieii H -3 16069. I DOW 1151370 1't < i ^ * i r ' - 1-r ' - r"v< ~ -- -- len Apparates wurden . ' ciTrrkgrisccnshmtlcoelrlsjtihUwenuuokrlrdlaieeu.ltrivDfe-er!-r. ^tHateexna,ilfilor ruenysclwoliicehxtiagu. .lische Verseifung vm -.;>>* egemvart von Nut ron- ^l 011 W y Vi ' ! -5 M richlorphcnol ; -Ij; lorplicnol unter Zugabe <4 OCHjCOOII \-a ` t j>JkctK\ycsaigsiiure :<<-*itTririrelrikkurapnheknt owl-atreIwn-. :!\ .elu n Kaliiiken auer;i n li-r iniuiu;; vu: J iitii Teil m it schneien s3i Trii hnrphcnol selb-f i l.itrratur MilU-iluiigi-n ~ ) ; lt'atrtnell ig'leivftiuhlrctU . h*a.tt1 e!. ` tl wir aller bald fallen f ing ge.ir'n'itet wnuleii. i waren. K ist nachdem Untersuchungen zur tiologie der Chloraciio 591 eine ini einzelnen nicht m ehr zu bersehende VerfallrcnsumstclJung bei der Herstellung von Trichiorphcnol vorgenommen worden war, stellten sieh die E rkrankungen ein. 2. Die Ergebnisse von Tierversuchen sprachen eindeutig gegen die urschliche Bedeutung von reinem 2, 4, 5-Trichlorphenol. rs! a r- P :. ,;.. -,rfwTiTi r *. v V\ :hv'v-. . ' V . . --,S'*"- - //.- -, : ;1 )- t%;!' .-N-- - J --- - . -. .. .. . . /. .... Abb. l. Cliloracne 1k* ju lir. ClcmicariK.iter, na*li Umianj; mit tetho. TrlclilfriJtcnol entstunden T ie rc riK -n 'i/irnti? Zu den ticrcxperimenlellcn Untcrsucliungcn licuutzlcu wir das Knniuclicnolir, a n dem H n n u x x u. N kvman.n, 13i:a i-X, L anuts u. a. m it hoclichloricrtcu Naplitlialim.'n Vernderungen erzeugen konnten, die denen der mcnsclilielieu Cliloracnc weitgehend hneln. Die Jnncuseilc eines Ohres wurilc m it dc-n auf chloraciu-er/.cugeitde 'W irkung 7.n unterMif.hcndcu Substanzen tglich gepinselt, das zweite O hr zur Kuntrolle nur m it du tu Esungsuiittcl 1/diaudell. Die Ver.suchsdancr betrug 3--S U'ochcn. i'.ii r-- iyt J i1 l *'i 3 1 Jt -.'3 ? ;< i 2 I H *j - isl ..... * ' . .. r. 502 K. H. Schulz: I V-- r M it dem von dem chemischen W erk zur Verfgung gestellten Tri. chlorpheuol, das als technisches Produkt zu etwa 00% reines 2, 4, 5-Tri. chlorphcuol enthlt und in 2% sowie 5% Lsung in Polyglykol verwendet . w urde, traten folgende V ernderungen auf: Etw a 5--7 Tage nach ]><.-. ginn der Pinselungen entwickelte sich zunchst eine m it flchcnhafur i | chemImisc< jvn auc. .Irm De uissc. I: Tzb- ./ I ..i j4 \I j .i .{ .;(it -(tl4e.e5b-nTr. ;] i Cd.-Tr | * tclicir.is ! TelracL | (symrzr vIVoniliTii. > llllkl !Ahb t. Kaninrhnolir lu(wKliolUtiwkuOLt iirtcicltlfypJi*cTliakicnrJaIfunir^.-u.mit .1% icvlm. Trirltluri'fii'uol iu l'olyirlyk-* j lor r.h . jilier.L- B tung und miger .Schwellung cinhcrgehondc Entzndung des Ohres. 7 /u Einige Tage spter nderte sich das liild; Die diffuse Entzndung bildete l)r. > ich zurck, und es traten nun Vernderungen auf, die m it denen der wim;.: m enschlichen Chloraene sehr verw andt sind: erw eiterte, m it I fy] <`.r- 'las:?.?- keratosen angefiilltc Follikel, die ber das Jiautuivoau hervorragt eis. so da die Oberflche ein reibciscnartigi-s.Aus.scheu annahm . Das nur tui: Tiiiv.. dem Lsungsmittel behandelte Ohr wies demgegenber keine Vernde IN u; I rungen auf. M-iu. Histologisch fanden sich eine aeanthotischc Verdickung der Epider mis sowie ein dem und mige Zob'udiltration in der Cut is. Die Fc.lla ! tu ili-r Walen stark, fast trichterfrm ig erw eitert und von koratotischen M a-'cu 7.x n^ofiillt, das FolIiLrli'iiiilicl vcrlnviu-rt. i 16071 I ' Untersuchungen zur tiologie der Chloracno - 593 I rung gestellten Trireines 2, 4, 5-Tri- Poiyjrlykol verwendet 5--7 Tuge nach Be ine mit flchcuhaftcr I ! | Im Gegensatz zum technischen Trichlorphcnol lieen .sich nun m it chemisch reinem, doppelt destilliertem Trichlurphcnnl diese Vernderungen auch nach Swchiger Pinselung nicht hervorrufen. Die Versuche m it dem Destillation.srckstand zeigten wieder die gleichen positiven Ergehnisse. In der nun folgenden Tabelle sind die Resultate wiedergegeben. | J Tabelle 1. Ticrcxperi(mPciuntseellluenUg nvteornsuKchnunnmgcelnicznuorhretnio)logie der Chioracne Solutus Strukturformel sreroOtrf&koUHo*ii ** KreebnUse Ohr toLxeibceirt-'t OH ' 2(t,e'ic,5h-nT. rPicrholdourkpht)rnol S(e.h'fe.Srn-Tisrcilcihrleoirnp)l-ii'nol <T OH s ` . + + schwach 6--10 0 0 -n -trundum : des Ohres. Kutziin'liiiig bildete X In* mit denen der eiterte, mit llyi'vi1 uHo.iu lurvurragtcu. u iiu Iuh. l)-is n u r mir uiU-r keine Vernde- nlivkuii_' i*-r C u ti'. dDeire FEoplildikeer-l ki-ratnti-chi'U .Mas.-iii T(scytmramchcllorr.bcehnezmolisch rein) cc ii-^Z JVt -cc ii 5--10 0 0 DvocnstTilLriicthiolonrsprhcclnoostland ' -- ; 1-- 3 + + schwach Aus diesen Befunden geht hervor, da der chloracneauslsendc F ak tor nicht im Trichlorphcnol selbst zu suchen ist, sondern als Nebenpro dukt bei der alkalischen Verseifung von Tctrachlorbenzol zu Trichlor phcnol entstanden sein mute. Ziel der weiteren Untersuchungen, die in Zusam m enarbeit m it H errn Dr. Slten, dem Leiter des Trichlorphcnolbotriebes, durchgefhrt wurden, war cs nun, filier die N atur der zur Chloracnc fhrenden Sub stanzen Nheres zu erfahren. Da diu Isolierung ans dem Rckstand aus ueren Grnden bisher noch nicht mglich war, versuchten wir, auf dem Umweg ber synthetisierte Verbindungen dem Ziel naher zu kom m en. Es wurden naturgem solche Substanzen heraugezogeu. fr die W ahr scheinlichkeit besteht, da sie sich bei-der technischen Herstellung von Trichlorplu-nol aus Tetra eh lorbenzol bilden. Diu Ergebnisse finden sich in der Tab. 2. Z unchst w urden chlorierte D iheu untersucht. Dabei zeigte sich, da w eder der unsubstituierte D iphenylther noch die 1, 3 und Arrli. Ulli. i`S|>. IS-riu., 1!J. Uli (Kuirrri'lUx-riihl) 3>> co * ro - I 16072 t 594 K . I L S c u v lz: - CJV 4fach chlorierten" V erbindungen in der Lage w aren, am Kaninchcuohr CO irgendwelche Erscheinungen im Sinne einer Chloracnc hervorrurufen. Von Intercs.se schienen uns w eiterhin Chloricrungsprodukte de. CO ( =Dibenzofuran-s D ipbcnvlenoxyd) zu sein, deren E n tste h u n g u n ter di-;, genannten Kcaktionsbedingungen ebenfalls mglich ist. Vom Diphc-tuith er unterscheidet sielt L ibcnzofuran dadurch, da liier zwischen zu...: Tabelle 2. Titr(X}K(rPimin*s.eiilluilnhg UvonntcnKuacnhiunncgliccnnozhttfrct)iologie der CMoraaie Suhrtan* Strukturformel knorarni%ltofr-an- Erh'elmiua' Ohr tcLxelbrielr.-it Mcratr- kunsru 0 schwach ,.; (+) seshtarrk dSeterllCuIn-g Asniticcohhnetire Benzolringen ein Ringscltln zum F unin erfolgt- ist.D ie unsubstituierte und eiufuelt chlorierten Substanzen waren im Tierversuch unwirksam. Dagegen zeigten die tri- und tctrac-hlorierten Dil.icnzoftirane eine starke hcpalot-ivi-: lu- W iii.niv'- Die tgliche J'insclung eines fiinfntatkstf-k- groen Ohrhczirkc* 3 W ochen /.um Tod m it der ,-V\, Tiere. uttil 0,l% ig Auii>ptieh cu flirtc innerii::lb von fatulen sich an der Leber -a bis us gedehnte. z. 1'. hm orrhagisch im bi! hotte X ekruscn und erhebliche Ver fettun g . Eine einm alig peroral applizierte Dosis von 1 m g kg fhrte zu einem schweren Lcher-whadcu, die sieh m it der von H ovmann u. O kttkl angegebenen Modifikation dos iirom thulcm tcstcs gut verfolgen lie. Au den Ohren der Tiere traten aueii die oben beschriebener. Krsohcinunzeu A MW.l 151374 :c ahmcrrKornznuirnucfhccnn.ohr onjiigspruduktc des ittstcliung unter den . rit. Vom DiplipnvJJ liier zwischen zwei *r\ l<y]it d tr Chiomate 'i ; CtUt- i U nlfiU I Bcoicr* kurtfea .>? ich ich ehr Utk Stellile;; ilcr CInAietollmi e ich e r ':r u n su b stitu ie rten r-ult u n w irk sa m , furane e in e s t n ik c * fuiifin arkM iick- -Kuif-difte.trliili\ebneur 2anbsis- m l e rh e b lic h e \\-ri mg. kg fhrte zu i AnH 't .t N x u. O t : r n : i. 'e r f lle n lie. icn E rsch ein u n g en Untersuchungen zur tiologie der Clilqracno 695 auf, jedoch w aren diese geringer ausgeprgt r.Is in den V ersuchen m it dem Destillationsrckstand, so da es noch fraglich bleibt, ob die 3- und -jfnch chlorierten D iheuziofuraue die eigentliche U rsache bei unseren Chloracncfllen dnrstcllcn. 1 H au knnte sich fragen, ob nicht hher chlorierte X aphlhalinc und Biphenyle, deren chlorncnecrzcugcnde W irkung seit langem immer beschrieben worden ist, auch bei unseren Fllen als Ursache in Frage kommen. Es ist vom chemischen Standpunkt aber sehr wenig wahrschein lich, da sich diese Verbindungen unter diesen Reaktionsbedingungen bilden knnen. . Einen Schritt weiter bei der Klrung der Ursache kamen wir durch eine klinische Beobachtung. Vor kurzem kam ein chemisch technischer Assistent m it einer schweren Chloracuc zu uns. Iireinein chemischen Labor auerhalb Hamburgs war er mit der laboratoriiinismigcn H er stellung von mehrfach chlorierten Diphenylendioxyden beschftigt.. Etwa 10-- 14 Tage nach Beginn dieser T tigkeit entw ickelte sich die Erkrankung im Anschlu au eine Gesichtsdcrmatitis.'D a der Patient m it chemisch reinen Verbindungen gearbeitet hatte, kann angenommen werden, da mehrfach chlorierte Diphctiylctidiozyde in der Lage sind beim Menschen das K rankheitsbild einer Chloracuc hervorzurufen. CI CI S J y r xu Tctrachlordiphcnylcndioxyd Stellung der Cl-Atome. nicht sicher. Auch fr die in der rheinischen Fabrik aufgetretenen Erkrankungen kommen diese Verbindungen urschlich in Frage, denn nach Ansicht der Chemiker ist durchaus damit zu rechnen, da ich chlorierte Diphcnylen dioxyde bei der Verseifung von TelrathJorbcuzol zu Trieblorphcnol bilden. Die Tierversuche mit chlorierten Diphouyhntdloxyden stehen erst am Anfang. N ach den lti~ln-ricit.-ii Befunden scheint dem aus dieser R eihe untersuchten Ten-.vebl-iiii'i.henvleiulinwd beim K aninchen eine groe Lcbcrtoxicilt ei ren zu sein. W enn aueli die Beei>kctte noch nicht vollstndig ist und insbesou-. dere der. Nachweis im D otiilationsi iiei;.-laml des .verwendeten techni schen Triehloq.hcnols noch fehlt, so glauben u ir doch, m it den hher chlorierten Diphciiylcudiosyiku Verbindungen in den Hnden zu haben, die mit der eigentlichen Xo.\c zu mindest nahe verwandt sind. W eiteren U ntersuchungen wird es Vorbehalten sein, hier endgltig K lar heit zu schaen. OS* i o n u i g w w . n i w ' i j i i v M WI u l i_ . If . ~ ^'I.m ia ^ i.n 1.1 i , ' u . e v ' u.i u w ii' i : ^ y ',tT ^ . }f -m m 'nj m9 L Wy i * t m 506 B.K x i c k : . Literatur B a a d e r , K . \V-, ii. H . J . H a i t i *.: Industriel Intoxication duo to pcntachlnr- plicnol. Industr. M ed. a. Surg. 20, 230-- 200 (1971). -- B r a d n , W .: Chlorakn, Monographien zur Zeitschrift B c n ifsd crin a tosen B and 1. A ulcnd oiT : V crl. Kdiiio Cantor. -- G r im m e r , H .: Beruflich bedingte Aktie durcit chlorierte aromatische K ohlen asserslnilc (Ohloraknc, Peniakrnnklicit). Z b l. Arbcitsm cd. u. ArbciN- S c h u t z , 70-- SO ( l.'i). -- H o f m a x x , H . T ji.. u . \V . K eitm a n n *: Kino Methode zur ticrexpcrim cn teilen Prfung der H n iitw irk u n g ch h iricrlc r X a p h tlia lin c. Zbl. A rb v iU in c d . u. Arbeitsschutz 2, 1G9-- 170 (1972). -- H o e >i a n n , H . T ii., u . H . OirrT t x : D ie Lcbcrfiiiiktion.sprfuiig m it dem Brom sulfthulcintcst als einfache Mikrom t h o d e . Ar/.tl. W schr. 197-1, UC-- 907. -- L a n d e s , E . : D isk.-B em erk . Donnt. W ohr. 130, 1101 (19.74). Ausspracho . A. S z n k a ll-H a m b u rg : C om cdo n cii hei B rille n tr g e rn ber den Jochbgen sind wohl durch Abschabung der olx-rstcn Zcllagcti der H o ruschicht m ul an- sclilicOeiidc Xcllprolifcratkm mit vermehrter Hornbildung zu erklren. D ie Bgel der H ornbrillen werden im Cch rauch an der die H a u t berhrenden Innenflche rauh, wodurch die H e ilw irk u n g entsteht. D a eine V erd n nung der ]Iornchicht tu Zellprolilenitiou mit vermehrter H ornbildung fhrt, konnte P inkits (J. Invest. D cn n a lo lo g ) 19, -121, 19.72) zeigen. E s gengt, nur 4 ohe.rtlehiielie Zciiageu der H o m se h iciit abzuziel-.en, um Zcllp rn lilcra tio n im llc te zu erzielen. _l*lu K e ller-A ach e n : K e lle r fragt, ob die hutig bei B rillcu tr g ern zu be obachtenden enormen Comedoncr.hildungcn. die lediglich in der Augcntinigebung gehuft Vorkommen, a u f einen Chlorgehalt der Brillengestelle aus KunsUtuiVcti zurckzufhren sind. E r hat diese C onirdoiicu bei einem Pauzeroffizier n u r einseitig an dein Auge beobachtet, mit dem dieser durch das Periskop blickte; die B ildu ng der Comcduin-ii perastierte noch jahrelang spter. ^* 0 . B r.iu n -ralcn -M .iin z zu Prof. K e l i.kks Bemerkungen iiher die follikulre ,,Brillcnhypcrkcrato~ e": glaubt, da diese follikulren Keratosen phy*il.'u!iseh (z. B . D ru ck des Brillengestelles) bedingt sind und erinnert in diesem Zusam m en hang au die Comedonenreaktion nach l'im tgcnnslihestruhlung. .69. B. Knick-Mainz: Cortisouproldemc im Grenzgebiet von innerer Medizin und DernuioUigie. Bei internen Erkrankungen reagiert die H aut als Gc-samtorgau ccwohnlich in auerordentlich starkem Mae m it. so auf extrem e Stre;Situationen, Infekticmshclastiuigcn, endogene mul exogene Noxen. An ihr als Substrat sind in be.snndercm Mae Grm idsym ptom e der ursch lichen Erkrankung. Krauklu-itsvi-rlauf und Anspreeheu auf die dwrehgeffihrte Therapie zu verfolgen. Dies gilt gleichermaen fr Systemerkraiikungen mit H .iittm auifestaiionen. wie 11. d a s Bocckschc Sarkoid die Lymphogranulomatose, Lupus erythem atodes und die klassischen Kollagenosen. m oi siew sid! etw ; Thr den 11.11 - und | auf: seil. SOU har. Enknt lu; 1h i *c\i -On*.l: | vt t kxv la lut trr i i V U- ) r*; ii ,i-, t it i\; lUt i! Ilr I E - W f n M u m ; vnm - n p j x ti ./ i i h .u i ; h 1S0751 f^mrn "STETST 1746 '"r-:-:,` v.y\ Scientif8icTTSraINnCsOlRaAPtOinoRnnAATSEre!b!r,ovri,cMe ich. Clinical P icture and E tiology o r Ciiloracne By K. H. Scultz, U niversity Dermatology Clinic, H nm burg-Eppendorf /nu,anmacfccasWcenapaffaatmetoniipnIpmttsifhttwvisdr(nnnonhmirhiihanruysnkaicapelcxxppnaTaritueaaegnsoaeioaovcxaschdoieTeutunTGTJnsbnTIayidnCtrrttdppnamtarurlamrqeunyoteorrrttnirutebieesseecdls,tecwhrlihhoueehnhuriecleeerkhruymdrleenclyrstlbtlsrgrerAtinraavaeseeesrnhmnrmerehaltehsxeo,dianeelocaaeroaaoteee.vprreetasm.nengrpaenplaenbsrohgnomrdhnobc,csioritdsdspltsrblfccaruacurotdtahtIHtayff;dhdoaaktifadmaaofu.okalicsdeilaaoeeUpicn.sctcilomeymerceiulneociiedrsusnpiHisaifieitotselfnhlttnntngieIseknslncspasnrrfyahedriyhbroionaaedwcilTaitnrteeeevygeosgsouae.cfedsoifaci,aslehtrcsufweteeltralcstinrfaathnxatiincsondeantifyaiufigtaosaintihantrmo-yIausrasennnfnoataetoonnieaosxhicslsdmpSimmsilicr,enlgsmunsdlstzdlncesofdteosgrnIsuiaiteleantnhmtde.lnncrncmeodbacvdoilpnmenmasunp)elspatmdrHeinomeeofeedaadfoomothadb.iuioibtesnitteanrrmsitreirfsfsgrecmclattdhtra.wcnmtwooebylehesymeoalcoifs,ieti.aeudiatftlGgpnneceesoeaypmroaeqseoyvaonumroerioeyihxSaploc,OaetnorxerxaaiyneDndsona-nc,iunmfepehrrtrrigiharnanseefzulglrksp,eaanacysreameenforde(ceeoieiainnmblvecndoasaseerdoott,rhnertsSmwarns.oofenoratmghshohtiieatdtcelftssdeealsi,dhdikmerennecihtroectireyolmy,il,iefrwheieentolallaedicaailpedipenehoiftsccudeafIyhsanynwtnducailihsnivymgrl,nsrdhuecahert;mmlmceon)frpl`letganifisctaaayaise.mcyhfrcrheemIrishbevovSopcidfaottbdpgottttlecaccncaiaehytuiscoTaaaeiosieoolTgrrdtceyecchnncninaoepuehntlseoiemrrh,tteohnwt,ktiabplsoihlndeghtth.ooesdesrihfenthehnltdvntvoledgiegfgrtahal,oathupt,ny.dmolhnnaidaesetdeehiooesladliiIouseitntuttpehrlatgooa,y,urniocirniteadinsernnciimirezosigsccnahoaeaaotcetehpngtupared(msnsfnahtta)rapi.tmpieinc,sieSrslnanyephltrcilccr.oicwnodnaanngaftndelci.srncnryoocseat.BrmhhteothiaaIcgssantndpuswem,oogiaeedasonsehseehnneneneccvhllnccBiePgdohnnssm,islpmoo.aaaotedsiieaeiomoeleulntpciileomansceyrsttiarfyvn"rrrolaarussoionadmrlonoeIieliarslalreeesmiipnpaapakeearwtrincnnlinllinnisaainbmndrtfocuiboanyoeiofnlintmersshdpinrotc,eemellidansaoskeoIuiodrtivl)negcoofagrlirdnaaeesngnuroetirmgoats.pe.bycartanldeco,rrhteaamtfioerdsespaeeiieclyfdanaththcesrpduetoaoou.lseiadGntoFh,txeihsotpneiecldcadepobdetfenophpndfhlstlesldfttieerhrryrulsurluihyberrrHiaooonihirapeioxvepotedtatdvieaeaasnpnaltcoreirriitsfoasrftmoeeqtcciioiearliantreollocielteeonsceatysftcisdnodoaseoyetikuidrftnahrfnirtv,imdontentttwtmdsmftcscoofu,sxsnbel-mtnsiasheihhnifoudeeneuate,fsdtuhsooeatlnmiliiietiroeaneoceoedleerrsaxsioiseneinaotnhrnfnaelnanlrt>ssmvlranenneactrexslrsiaeonhtd.aeeretteeelilr)attoceegtcd,st"trtl(ciosoayvtyrw'ldhater.aysesllcwossehrqaaliieogTntxceep,rccoogaaseamycotsfalcahinfpevuccnprisohdio,ntasofctshnerorituhnpctsrdar(catoeie.lehdnuuhof,iefytenfeuchutieBdogiuiradvsbanilcornspcivtssrs,neoerwoeosnnCfeceftrhieitheehttautertotaeocicpoWefsmlfwriodchafpadduowtldmeoeteoefnnofnveeorlevthyeerfahsiltomeeeiolrmvldam,itnsmhpicdconndidicrniciaketlaedysiclneaxecerdeatep,atoiclsruoenepeekssuiaouphsme.sdecewdtwnmecbaohnnourumdnilrtreriwerdftcopdhesif.tdaiatcssalnli.ifdnAi1asesttr.oerh,oemnarftyohanomoos,lhceiiunce8,dhboemilfanTgapor,noctrondaokrfreBnTpoe9agsnyasDherelataenmoeneranptdtteahf,,li.Ta9oauauiftlregolhecoesgrontcegvhllaeriontlnap,orlianiyenivdyefasdoTpacallhgsccicelmWloieoeietnerdsfylrteneopefeaydvotluuslhoslefoleerehiosnpeannudtuiunor-dnntekepaeioe.prtealak.qdreraacrrpwstmroedhcpos,mndtrdshrenaosm,erolcycutuarionalecohiBooriniureytostcrteanaDdstthemknminebnnmdardaaafifneeopoiealtnlvrlrordtolnasuvcetstgctl.hnsrcoaadsnahesanmooodaitiaeiainttmnmeuntitttlsietpsocnonenelthutenhinihnnurhrlerbiItataraoageyeniosilaieylssyyddingrenireaenegdiessgagsseecalscslrl.,-t--fl. cn o i-- o cc y Mfl " U V . 0 Ji mm JL * T -. 171.1*?.l j -v ' 1 - .,*> '- v: - 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Cl, Cl. 5^?-' .... *y-T; Crt O ro i-? ... i Swr:-..- S r t f & f r .. r -; * ?>. t-v - cr i t ./.* ' I i W{-irVv-"`.'.i'ftS.wtfc-.~'-iV'.'1!;. N aphthalenes containing 5-6 chlorine atom s: -C !i Sftr'"?*::V-t-l.lf-iC2S.-i.il. L- 16079 p.. `>:v/ jp^i P.|J" A' -^7- . *. *>/ *.r;r u .i"-* >7. i' \'.:... jtfSib tt : ;*. .%..- - ji "'' -^A:;rc :'V - _ accesoloychsnagnuslIluoyitnece-:.cammac'lj;ou,vuaanseinsecnrilewfudrseaesaepsdismlotoudlannialta,ttsigissoioebinpntlfeisrnssyothiocmctovoehua,mtihralidipinetotrotiuosubcIsxksneiiedncirxnsna.eaotcteimptSooeraUminndinrnTamtcEalletwyOtehinoAoiiatldirTnthingecUsvadtBonhbcsElskeeetv,hrienmtnteaoesaihdxnpdiotiegehcechcoosiihladnryollneolucryortmagtoisnhtxaeahatisloetciwensodtilasfseiuyvrsbsaenrursreasortplpaeamrenpneacacrdsntteeeeidsscndnestenne.wcredthvhuTlbitorcbhhuorhyees- '--v^s\c\JdpQtTtBDtDtscoCacmtp(lhWohe,.hhtouchchfoeeaouumslBeeBBBaeHGHgDHKHhenHKOHrSSSSTlSxanowIedsl1sdrrotniionoianaiciecckoptrncoho6IrrceleneemrioieoyOeccorn.gmaimhdiusaihhnigh9D-lh,lsersfrrtigfrvormnnle-enscurtxzdAngcuuumeenaebmlmaoI.moaleVem.egcuklakeabncnhr.selltaetscmeie(nflrft-daIrlzze,r,yaeimto8ueft1,hr,tnehfitclySnsddke1,,nlUagreWngetr,elej,9irpt9lyhebWe,.d.,unt,9,hdm,gWhn,dmHdHcr7,nKao5,g,n.eEK,.,nhetW,s1e,HGD1,tC12fJr.isap..epc..KWc.cdi.ie,Ta9.vh(g.,2M:0.)mog:.lyr.rH:hedh1J.x.1oH5rIHr:8,.e,iEy9lIo,fne.gC.rlora9IIi8Aaei5aVer3rKr,C.CBadondo.n.Mda..KiI.dc2r,so.tnmoaU.:(nnfrlr,:.umsr1lhalJ..lih.T17,md1nona'.moiatt(5T:ad9.iaccae1lnU..)ylP91.iac:lSdodcaCnc3n5r:orttn:HFxOnl9mih.Cn9n5KhetinirO8m5oaiuunr;Tc.,Kpcdoo.case3o6.sd..cyerWOwDaelCrp,C.Kona:eeeclni.K4iub7ng)c.lns(Wuoncxnrnrna.aHhi2Hi1.luo)aAilA.SNpct..ntbgPsyiitiesdnc.H5iop0adapcnhc.incas.a2.oglBiec.iiDaat.nDfnhi0tioaicaeihnsa..t0or:lr)nshtsJpoW(MSigolidt1latr;raMon.uou,rhre1ech..ciWereetSlI)csc,idoclsrra.ae29naZh.na.nnnrzcafl2ohnwmccBinaseedct8A4cltrlnsbhst0CkKqnieuNhueoesnotfan8cto7iolcdanb,ahclfeuou:nlp.asurlomieheol)uxeenzunetomoersewg0ncifal.x.lnr(fcrCsu:ifg,(e.drzoepns7H.er.td12icfpostaMcasaiimatm:nenlrhxeotH00CCitoaAi.ec2r.lllnrp:oxohGrodae(6i-pnoe5tnnuir1aonOdehlh1efUnp,irntb,DniAowet.1o4anIenolnbenmx9lrodoouc35nr.)lrcocrtiendcrneiA:3MpiOS.lsefhgcSn3bthhndce(rrmeoi:si/i8uembu7.nu91Ttmceuih,Snglonc,u.Wfcsnhr)roypen9pe,tActthnmpm.soiBoebaBiayF,(so(rna2pmeuOotdelum1co1tnyit,dext.er)eeta8lop1nenoteCcif9mraetsei.cdr1dgnoidp)o9loadelaathnWtoc5mln5cc.o.9a.te5onrDntextlsalt7cu7hi6taDygcK9leWutooeaet5apuoastba)o)h5pab.leheidiinnl,trtr..lmneluorene.oroartudrlsiieondbtmr7a:serrnrnrttndtcsnadpiesmkaoigo6ile.mahscn.uoakixpTtiahn:xn(Ite.tirnfanPptannpneoo(eBneesh..iAso:Wtet1hoahrMced.dnnisieOe2ranmc9lcrwtarMytu(tdo7shschiehaaJ5Cct(rspetcnlj,e8dhioac.Plesaloca5hetionrhhol.,yoelf1acrunrdp)oh)eencrip(roproj9t.rc-iKpcgrcb.y1nhoteiamcor5lhcfmoenaalel8iasosnaedeulm5hoetbctgniain89lsds5au.iirnmGlclllotocnon4.awi9o'noeueteeee,iimlf)i5tened)kgamdtraacdtCZciii.nwi5hanoiucittlaotpnbcm7.oiho4lt5esfslslcoehelaa5(n-B0o6.'rht.shrP1rnley,tprsfp,pgIb.yhmeei.xAe9daonCMe0s(y4oceddrirpaor12pysgnStBau3hrpreoHrooseso9fb7ca9etnho6fnaaoneciaxrnps5yhecr)letbcncfrifaaacdyih;ioag7nome((unaelgccrthe11r.ebg.)rsep,rbcftanecal.eermb99ser)thKoaotsfameBnuonnsdsafo6i5ftlrnueoyokcnlxpnhiotoao17naiibnssadbersndinihdrnodr-))s-.yenec.ly.,--..,. 16080 OflW 1 1 5 0 1 1 3 ?':> I yk. /< ^ ~v>1"'j . T v',.r; '?J;'.W .i; . ' v ' 341 GCpt heleeTAi*Wnwn1trsdineucnydarc,bunbmrhneeM-tlhHsuor is:eartny,osrdgitopOsi.Iehfntbc6oel,tc,snfteutho1dGrtpe0l.h..a0te0toAVai2o(cu,r1lPonctt02mrthaheo1l.opHf8rM.on)a:du.nDmaicnsilPrd.eb.rsaPuBo.sZrr.feogc.sifBl.2eDr0d,1o.ru3F.u,eusSK.sOot.CoIr.aH(aH3c.r0i.ti5:lSBo2cR)roh.ieeuushalezrt ea,l ndr cgUhonhr iyovSdneorrhostnhict,aeyrIbnt DoogxneeislrchmoclalZomtbgol,yl.ofgoofyr.f R etort on MethodolOoilost,faonrdCPhalotrtyinaAtceiddsAromatics in P ats, sADHi.odeBnam&yltiohnJ2fOi0sS0FHt0reoaN1rotv)idioRcneCE,, ShCDeSom,enpiGssau.trrmtRyme.reaHnnPItdrGootGTfeeIcNHctihoBennaOolltaTohngH,dyAE, EMdBnu,uvcariarentoaidonunmD,oeAfnaVnt-aSdIlDciHWenFeceIaeRllf,taEhrFSeSoT,oeOdrWvNiaacEsneh,,diPn(gDDutbriolvuincig, ABSTRACT I * 1 * { i epmdcdwrtctmbfectwbsiaartbos2ctttwotpoaeoeohndoeiaihcaivoriiiienliif,fhnolhnaoooiiistgoTliuAotl3ehrndTraeTnalCTrAcnddislernduteexxesnsmcrlon,eoadtul,ddhassrhoenh4o.epae)lEriuileanbodprnuipcielstenerlporceea,gn2ecpbnoatbdlasebFCaavtm.hivohlhslol,rinish:irtdtIeeuohy3tbeirec-le.sanotte-mnynpmiwofodnliyoaiero.ccefelatswoslrTfdneigaa4iuoeelxzcairtizolfaoripiPncdrocncg.,mrbttff,oihpoehcrdorionnnGtantdraohcsbotegaraptcpdeemioet-epei-eaferdtCwoilsieuileteyrnctpiit-opdqrodcaomfcseinhhisactoitltnreoh-htcil-ssh,hEyphuvcirnydi,gcraaycs,tdfdtdpnmcpheotycletnilertaipehClnrrasotinlrsocleoc(crflaeroaefayooridtsaGeiotacoo.piren-ehdtarrqoiisalapi-irtdtoncxcxcoGadhovrcseollrosecwnhLdeufuddcOtiisefiishtaoopppoaspoenludaufsuupenLeor,eCeetsyerliphsmrnbthstdwterassdtr.rn.rooctyCfuueohceghg.eeesasuceeea.cmodrrdomksfihrdcpioanCTueonmucnvtcwmtoeoseeefrooemelAnehnorwotimdtpode(hooEncrmrbdsgdhfiias1iecollldhpwecoreherfxCsotosspoFieuhktto,loecarcihocteftcmoinh2etpfIsrtetptoeLrhgsthnchadupimnhwlhnhhnikrfx,ocecinfmoeokeoc3dCvtioirtlooIoesndptiidecbtieaositorieendo)ceeflftlsrydenintrhlr.okwclcmr.ebirrsudahnntxecoroecnesmoahahpefanoIiflecbetccsIoioiivswoooBttndnntplasalihszicttftusaanblterofubelonsihfysharcirhttoeueiolnotdtzeoorlttcslrosfneiaiaebhane-aooaltooutaeodsotatpfshripnrbgnthmieounrkohoibcrrrdn-tdnaassnptnmolni-eodoarpgdorIsodler.odcyainssdbldlusnngeecnb,mrpe-alimooyareherfidirrldascdqTceaeefehgtnuianolwyhfnceistoa(entiinbadvcbnnuptoetseohuhixoooaa4tsfinfteutosanitkavceezaieatnlterhoiclscxaleinn)tme.sdurltvootodone1ttsproytlotiat,neei,weiaptdprieirm-nofs-tevrlpolfdscdRodeieoeipoby1csr)oaialoardidsorveslnoascfoereant-dht0ele.snodrfaeee,rtfuceddednlpniGistiGc0lchayroduhpmyninimcnibadioslirteaeedmdocdcaseiorcbarlasiLeLeetdtyrnnsjnaoaimlnaeTsteaexivefiiihecdidnCuiiClgngseo.ntnnylanvctttsnndlo,ehaelszisc.chiisqofudpffnu-tstyeunmzonu.vvaCseooorta,itMouxtstrfcrn,torr(reyreneehbh-amec.irsthednaiimPErafyiobpr-el1iswreaceinefstofdeallospfstioopefCn0o-etsToleiaoIaraeertncpod-syet1elnf0ssonioerncmrtrB-syrdsyohadtcnetftal0nori7somGuayifutaoboiodcdonieadg%,i,tlppoScnhcbirdsxomneahotLrmedlsccdnpethxr(hdetphteaytyfti.lfriqtehiCiofuCeavjeineleponspoinmeeeaologeootnnuv(slditssnnsi)rtzcsghqnoppdsEnowfecau0rnussueetaouutototIoors,uwres,tran,lF)cstrtcnpnhucail2(t-ioomlleiw.tiopcooshanapceyyh)oiitdrbin,rmaoipcmehcm3csoonnndnhlie-cahecefadeHumhersonah,adlfndl.htittideni4dgdaeodaietirotchrenctcoioaielngawl,oinoerrmotorrrcd1odhfkotodTfownrgceiodaltogcghmxht5rfehrdycsenopsreoohhpotuconreooaoi-eameoduecdtaacgaonlnutioelrvhsoddsrhmhfdteecrttosreltgefgtfswmseittuoei(nieiiethateoecionrihsrrrobboas5irumrulcn-nrvomiuii.yccgtensrieodgen,eensnsm)vvrrhhamosn2lpaercrrpneuneieocieaaatrr.lailnhclclatepvzzutr3scocasoiftittrihibpilhafeattceocoai,iyoehrcnenwneoafmacaaioa4oevvtthitiofnxlom--arrlpiarlhucnrecnnfe,tertodppaoeaenailoamo0aviicsscaykdipidddncydaccesrsl-s-sl----tl,-, (! i I I ii t { 16081; * *.r-V ' r7..iu\k m 1 132440 1748 INTERNATIONALER KONGRESS FOR ARBEITSMEDIZIN INTERNATION AL CONGRESS ON OCCUPATIONAL HEALTH CONGRES INTERNATIONAL DE MEDECINE DU TRAVAIL Wien --Vienna --Vienne 19--24 September 1966 PROCEEDINGS r SEPARATUM jL&mz DOl/lf 11 3 2 4 4 1 r 753 AB-1B3 OCCUrATKHAL CHLCBAOC MJUtCQS K. ET., H.O.* w l DONALD J . SHKI1CHAK, K.D.** i, t Tta story of ehloraene 11lostraca* got of cita problema in occupa t tional -hnalth-of on o U elnaletl causing double in an* -application. Actually. t h a n re a nabar of chemicals that art chlnrnrnisgsas. Host of tbaac bava in conaicm a similar c k o l a l eonfiguraciaa. aaamly , they ora 2 ring chlorlaatad compounds, oaphtlyflenea n d d i p h a n y l s h s i n g the anal rin a truetares Tha rabile laaltb Sarrio*`a Division of Occupatlanal Snaltk baa boon Interested lnehloracne since the middle 1930* a ben morbera mho-made synthetic maxes dare loped an son* Ilka eruption and llrer danesa fro* esposare t o chlorinated diphenyls (SrIm a m , 1936). The ocne -occurred not only c m the face ond neck but also on corerad parts ouch as shoul ders cod belt line mfaora conraolnatad clothing robbed. Tbs eoatanlaaud clothing na also responsible for cblornene la the mifa ond child of moa of tbs m o rbera. Xa addition, anna nf tbs morbera with chloraeae -dteel- oped oentp yellor atrophy of the Hear, presumably freo Inhalation -or percutaneous absorption o r both. Chloracna mas first absented by lerxhelner in Germany in 1S99 -mong morbera manufacturing chlorine -clactxolytlcally mlth carbon oloetxodas (Carocxl. 1930). duericen -experience with chloraeae daces bock to 1912 mbon nsieifsctnre of oyntbstlc mames bagan. but there ms re m o published reports matll -Schwartz's In 1936 (Scbusrts at el.. 1937). tbs subas quant empericaos of the Public Bealth Service mlth mutbreaks of chloraeae is.aunmarleed in Table X. la-addition to chloraeae -end llmr -damage, hyparplgmantatlon. hirsutism, porphyria. fatigue, aod irrito, blllty have been noted occasionally. * D. S. Department of Health, education, and Welfare Public Bealth Service Division of Occupational Bealth Cincinnati, Ohio ** UaDPnaredyotnfrDeeoseiSspto.taarrMtt.meiDecUnhetipngaiaorvntfemrOesnicttcyuopfatDioenrmalat&oloZgnyvl6ronSmyapnhciolol loHgeya;lth i f. DOW1 1 3 2 4 4 2 75* TABLE I . CTLCkAOC OPTBgaUS OmtATIOH manufacture of lynthitle as* (Schwartz, 1936) matexial synthetic chu actcceh c chhlolorirnina teeCdadndaplphhtehnaylelnie able atripping (Schwartz 19*3) B e l o w InsulaClan chlorinated naphthalan* -Metal catting chlorinated cut- (Schwartz 4 Barlow 1942) ting oil -chloronaphchalenss hydrochloric ac l d n a w f a o - enaction pendaet unidentified tore (Schwarts ot-al.. of ooal tar rL '1957) and salt l 745-T swnufacture 7,4,5-T herbicide r (Blelbcrg c 1. 1964) eloctrop lacing 'asking chlorine cad naphthalan* dacora tion of bant glass (Birmingham. 1964) -plasticiser In glosa ana-- 1- chlorineCud dl- and trlphenyls barga task repair (McLean. 1964) hydrochloric acid wnldcnclfled and rubber u m i killina (Goldstein, 1962) 2,4,5-T herbicide bottle asking >ld lubricant ''unidentified Outbreaks of chloracns In chemical plants mamifacturlng 2.4,5-T herbicide (Bleiborg ec 1. 1964; Dugols and Coload 1956; KlaaUg and Schut, 1957) and recent reports to the Division of Occupational Health of chloracns among barblclda users, has prompted ns to attanpt to iden tify the chloracnegenlc c o n c e a l nanc(s) Ip C B f t r c l a l 2.4.5-T. Several laveatlgators have previously worked on this problsn sad have ascer tained that^ire 2.4.5-T i s n o c chloracnegenlc and thee on a cbeorecle. basis, the contaminant nay be a chlorinated dibenxo -dloxln (Uaalg and Schux, 1957; loses and Krirek, 1962). The usual laboratory Italicstor Is the rabbit car canal in which chloracns can be produced in two to three weeks (Hofmann and Menneim, 1952; FI-- brick, 1957). The hi atopathology ia distinctive and ainllar to thac of hunan chloracm-- -- taplaaia of sebaceous glands and replacement by keratin plugs ai^ cysts. Using the -rabbit oar eanal as an Indicator we have shown tha* three different brands of 2.4.5-T herbicide are chloracnegenlc and tha p u n 2.4.5-T is not. 16084 v DOW 1 1 3 2 4 4 3 795 BIBLIOGRAPHICAL BEPEKEHCXS Blrminghsn* 0 . J . (1964). Skin 3:38 B le iAb ercrgh,, kJ .n. ,W 8al9l:e7n9,3M ., Brodklo* X.* itad I. L. (1964). C aroIs-x*l***L-.O(f1fl9e3a0*).GeOncecvuap, mpC.lo4n3a3n. d H ealth* v o l. 1. I n te rn a tio n a l D ogo6l3s,:2P62.t. and Colonb, L. (1 9 5 5 ). B u ll. Soc. fra n c , d arn , a t ayoh. G o ld ste in * 0 . V. (1 9 6 2 ). P e rso n a l cn snn nlc a c lo a . Haaferlck, G. V.. J r. (1957). J . Invest. Per. 28:89. HoffnAarimte*l t,eHa.cTh u. tarnd:1N6e9u.eann, H. (1 9 5 2 ). Z a n c ra lb l. A rte lts n e d . u . Jo n as. X. L . and X rlsak , ft, (1 9 6 2 ). J . I n v e s t. P ern . 39:511. ' tta n ig , J . and Schai-...L. H. (1957). D crsueoloalca 115:5*J). McLean* L. Q. (1964). Personal eam n t cation. Schwarts* L. (1936). An. J . Pub. Health 2u:5S6. Schwartz, L. (1943). J . An. Had. Assoc. 122:138 Schwarts* L. and Barlow* 7 . A. (1942). Publ. H ealth Kao. 57:1747. .Schwarts* X,* Tullpan, L., sad Blrmlnghaa, 0. J. (1957). Occupational Diseases of the Skin. 3rd ad., las 6 Feblgor* Philadelphia, p. 568. DOW 1 1 3 1 8 4 2 r*vj f f J ... yhe preparation of Trichloropkanoxy Aoetic Acid Avoiding the Formation of Chlcrukne Exciters 1749 161 pago Z Our synthesis of 2,4,5 trichlcrophonoxy acetic acid runs in the following stages l. TOleiaarobBOatna -fig.- A t.traohlorobanaM. !'' ' 8. Wtraoblorobensan. trlOIaor0^.m,l odltts ` ' Autoclave rosetion b. .Evaporation of CSLOH . ;V . v ; . a : 1.1. . c* Water vapor disttiiilllaattii<on of imiaola d* isolation of trichloropijonol by aoidiflo&tlon end subsequent distillation :\\3r Triohlorojfcsnoi g g g ^ . ^ ^ 00* 2 >4 >5jtriohlorophenoxy- '* 4, ' acetic aoid sodium 4. Additional wording up to pure crystalline 2,4,5 S-aoid . . <.' ' r- ....... , * ' ' *: f *" * / * * la our experience the cblornlno exciting effect on impurities may bo traced bad: to by produx ta that e&n be formed by the usual conventional process only if triohlorophenol eodiua or other alkali salts is prepared from tricolors phenol,-purified, *and " worked up further, and If. there .aro thereby reaction conditions** that are similar to or- exactly* the atuao as those-of a salt melt*' ' f * . : * , / . i - : - . ' - Proa this point of view with regard to the formation of ohlorekno exciter for th individual steps in the method, the following lire.valid ^ ' ?or 1 end 4*_. Those stops are not at all dangerous#- ,Por 2# : *; . ?he chlorskn exciter may bo formed at this step For 2n#- _. la order to pr*v<mfc this in the autoclave reaction it Is ncoeBsary to avoid the super* heating of the uutoelave contents (highest .-- teapar&turo 150c) and in addition cars mustbe taken to aaou^a that tho work ia don at ',, the greatest pegaAble dilution with methanol. 16086 1p6s1go 3 . For 2b#'- vcftioenheralsmoptsrhaeeodrelpabmhtsuhoeerontouthohlaldsanhstoooblduteihdludkemiesndptwoaitlntlibgaleeletxaribkcqoeueneaind'advt1hrot0hyei0dehweCddea*a.itoteirtnTiglthlheaoastftuiomti srapi~ ,; 'F, or 2c *, .. ' siTttnohrhielocurthhwet ialaoowotnroeio.rnlalcvse.abIinop*eftocrn1rtlaheetecidomeinssausmtsa*otiraflylb*laleteihwtfsied*taootnsneporeodf'soiaiusnurmi bdsdtluterrbciivhe(coihnaar|lgdowndrooeaq}dyfp,f hct'/hhtehaanantogl e i* : * ://. For 2. For/'S d** >`. f-.a;IaeIannnnxeddootite'hnhateoereei' sera'*drt/haystitoiesb,eattlpobiteleel'.`d*iassdfeat. woeilroitismttnhehe.,d'an,a,`tolttshefohreolt*ahppthshe/ooeoesdWrncsiddrioubuelim!#r,,dlseet.ittf^l'oropl"irahcp/techrin.hotoloohvlnlroeoonri pvttaehktisens'hsneeiolsl. . . co *-- * 00 CO *.v :: '. tho condensation of sodium trichlorophcnol with. 3 ; . ohloroacotio aoid sodium should never bo eonduotsd ::/; ..>/. in AQ %ans haonuhlyddrboeu'sa vmoeiddisu!m*in Aa lclonccaesnetsr*ation above wbdothefeiestshtttrhtorowItynoiaocthhaisehtvlrloooorvrbriadatyo*kpanbotah'reutiahsreeeon!'a,oxlifendcotgidlht.tliehoatriawto.j.t.ni.intaigs:oem',f',dm&a,myiansyobtrebeieulcetlot-rimxsnaaielgcihdseluonoafbrrfb*is#octo\*haa*uenntdcTieethhoienielret*espfeaiorsnprodetpve2itorootltaieiitn/ssi-l.e-;.;; uSpethpvoinoe*in'nc.int,we,i*ao-cttroh-*tk:maho.i.npetigcelehrmealtoepa.rlreeclayartkia.obnctn*ulee.orjsepseeurxdoofcdffiitaucepocirvpteea.nfrsrrhtaolo1tmy0vu0es.vseCctsee*ln'epa-ta'nsiinrld'a2tcseeapavdnri'id.etd.ee'n3moousefshtooi tbufselds4hutabbigkel.heimt-nvm/aotrtehkiloeatnditn g vs sig n e d | Veyland '> v 16087 DOW 1131841 1750 161 C H* Boohriager Soim 22b liigelheia am Rhein Owaany Bow Chemical Company 1714 E&ataaa Rd. K 1 land, Uichigan USA . ; Feb ruary 11, 1957 Our ref* Dr. Vey/B - * * *1C*- * Raj The ohlorskne. reparation of Trichleuphenol Gentlemeni ' V-,V ,* Ve hereby refer to our 1965 correspondence on the above " . : seuxbpjeercite.nceAwt itthhauts.timeyou ware kind e-no' ugh to sVh. are your, i Sdaa *ibelnts-lyecepra.oitpootuoiy.rfoo,,nuoc*vonan'ncvdlouraskrioenona, cvcao:crmoolpdhlioinsughldincghlilkotreh&akttonbemyeaaxktectiattechrhesi'nrgheasnau lcstohsmoaervttaoil \ -- yVoefxeipl htllaroniapcaelhstliooothrnbaoetp, hwaoefen.cihoiwnanyrtteer raibbecueseetttniioctnoaabyctloeoidu t.tho*negdaivassessuuyrmoaunecet bhoyaftm'ttehhaeens scyoo nnf ttthrhiebissuisti o n ' Vi ".i:,- S in ce re ly - attoJuK , Mr. _ t 4 16088 OW 1 3 0 2 8 EFFECTVSoOIFX2,4,5--T ON MAN AND THE ENVIRO\N4M.E7N5T(1 HEARINGS SRUEBSCOOUMRMCEITST, EAEN.nDOEFNOTItHiE: TENHEEERNGVYI,RNOANTMUERNATL COMMITTEEOPOTNHE COMMERCE UNITED STATES SENATE NINETY-FIRST CONGRES SECOND SESSION ON EFFECTS OF 2,!,5-T ON MAN AND TH E ENVIRONMENT A PR IL 7 AND 13, 1070 Serial 91-60 Printed for the use of the Committee on Commerce Cl U.S. GOVERNMENT PRINTING OFFICE <s-W2 WASHINGTON : 1970 ^ 2 4 1 -2*if \ 16089 Cn). L 241 BlDLIOORAl'lIY sfoddzctoGcSoiAJApa4f"CAiUff1fosatsehahTia.ierfa0n4xrpna.-ls<cOsxtut4d2368571--n1to1911vi12eti1111122C12222t9dsie.uhnsAletaice..e(g........012de8345m069A5i703de214,ho-1c"ehtmaicekvm..au.....m5...r..J..al...i(ncuineBFWsCKPOSSENiseieooea1a.s6t.chcAcie(WM.HFEAYoADHDnoFMriOccoSW,prntrldnc9cakasar1tavtA.,aiioseSoclhofiOthmnpalntlds"0gndbmenlluoai9tauai(.crernwiitocofeRlmonomxttgoel"tSga1de1lcreaeIrnucriCe0cn,ieiyuodetcc3ddnltofcionmE9mrfr,ekn9eos)mdrcltn.agh1zniascl.t'0ehrr,,ioeaie,pt5ru;,.,tttp6,rtChhd,,nelorliaWi)t--toCm,,IotCtaracarSeutn,raaicnoe,1op"Vl3oEglcSlfGeGs,linefDtnhnnr,SJerse1neh,klnnVifnv.aaSPm)yrr.ooriis..a,ieFsS.a,.",9,i,r,,e..in,e,tei.rcoat,OMez,.snp,c"rJm,ccAen.m6eeA,mnndHCMeC.dfdLoTda.REAke.keFRS.t4p1SeLRcdL1W".(siea.tCd.giiA..t.ee..dh.1...sDl.i..,o1,..ci,s.x.o,C.h,,H,rta,p,ertnS,s,so.oEs8e..epD9hirSaWCi,.hhfm.eCece,eyoC.TrLltasooGf,stn-u.ecE,5rFdlDioueeesytietltSa....4uiRnc.tc-on.,,tt-.atvlsee"Scesnta--fa.,o,ritild.Hehs.2trMuikda,eboef,f-nreaccte,tamlrscA)negieanatr,2'fheetnllern,yaxfl,taSssfahtdonke3o.Jeoollt.l.aDeisa,r3Gi,afltbln--,l....sea--nihS.rictvC,cdteoc--"a--..tsa--po"on2l(newldshal----3atvoeata.xaehs1eFlyJamcP,oa.fFfoALgsi--oJlev0.elnPq--nra(nsnna9riliJJPt.lo--llol.r(rt2m.,axbJicJt2.t--sgcsooi.y.u..oe.n,o6dtgodIts--nzfh0"oc--c--1s..ckiio)hJeA,2lmr,,ud1anugoG,cof7,AknWhe,7yuAot..,Pn4ipati)elAJL,oinmSceA"rDc,PinDntbDhedlp,metGt..6moWicer.Ahrc.tJkriA"ry.ddnDimeoos.ore,0urnk--s..htuti1--ya.D.t.(e.so,ygOoorsrAs-u.cs.ogb1,i.OJlo,iMnCcgc6p.isspccrexVetEOEnlafxI(u9.BcmpIcSohh2soieMroutif.akedd1CbHiinIFa.il6.as.er.yer.cFiicirnw,camC.l.,cerce"9ulycieh,celto.rc0,tr(ll(l.nCt.dni.AmeOa..5ekdrsiilktP--.1,tcsope),,aVOCf.c,SneeiehrOLet;ht.,n8Suime9nfMngaxonoaiseJetsdacAl3e,nfeet".)nnoJfbc6agrirtu3id.,..4durtf.iptdml7f,iete"Hc.i,dids,ief1n.s,7torun.5eeclRe,dmdernraAa.tni"tD,t)e.dr6madDS."yenemm.AuOairfWAi.lcPA.c1.dAsn-gVspeocny--.id1nSfmCtoea,A5t2'seooaensgbeerc,pmroDa.3hrScosa,2bu9i)dmlo,drn.uroewA0)rHtDocraoedince,9.s.igsdeLeos.H--ed,3f.il0.3ccn.cyaitmnl"i:tlreo.iomdS8.us.r.el.8ear"iso.Nni,A(3.,,rIarCer2,mau,dcyc,,eesr(1.nfdd0ewC.caO,,31isasrceatalao9S65,c1reBiia.stsp,7n9mnilsfc4Rifeov3fSs62t.73nnrinelf2,treh3rdm2aetC,ls03m8e9M3zc..careg1coFiLm,8e--,Ntt7df.,f,)inh.l4.2Iireeea,),aS.ieS(intk1p.i1e2p1(D--e,AmniWe.ue,1cPActa12n"ehw7,34i"rd(escdstu9k.tnsor0"192,E242ui,e(Pgro(e.csso5nieNE,1df2,,952pmerofMrIrraaonsg9Aa,i9fu,3((9e.e.afnpo)Acnra2o."easr1)1rrf(,6n-.c9lc.)aaus11nmd,myee.--1csGaG9p9,0i"h)dgCCtn4lcs5dst9Onti,5i3u"t.e)a.1eoisuntF4"trrhP5,g.8Si9nobnauCcey"R5ff(FreS9ooo)T)sigfl1ct.aC1apti(."ccfm,e,i,Iu)ercli0eeu"e1cn9coaT..ohe,(niculd--i,d,l"9t"et1Iia3dciaawtirehttoAusricAte"mcFCA5d9tSettrterrhtJeiir.aoSseykg9rs6motte)osl"o.hKepaaaaorma,l,.rstr1)nunnmdcrcirnauIix.,iaouAn)AsiS."ntbsinsa"i4rp,di.nlncdenoahc"drc,AI4mr,sotAiCi,hcLysSdliehceiatitu.tah1.lpttaoosp.hNs,oteeostL,u--otd9l(aeiusitnxenoimnxtc.3oOrx6.unnior4rYbmoiio--sFyrskit0Jin)ycic.d0ensciti,ff,c..s.,,l., OccuCroAiTll'IOOUNNADLS INBTYOXIII.CAltTAIUOKNII,OCKC.UIBIU.--IN-S-Ol-IU--ILX-Z TAIINEDPUllO. DSUriCETOIOELXREORFOC, lIIlLAOMRUOUrHllOENOL INTRODUCTION, GENERAL May 20, 1961 phIennotlhs eh alsa sbt eefenwthyeeacrasu,seprooffegsrsoiounpalo uwtborrekakisn otfh encpurcodinucatitonle aosft cthhrleoerinWateesdt V: UQWT130286 DOW11 3 0 2 8 7 .L 242 tmd0pfgtAcssosapcmwwhcnlaLpfrillovrcpSttllG1f(hoiiohraloteoeeieihoouson1rnfiheaenaeakPavirifoeaegavedwvgntear1rOTAAOugntcarrcddoDnlyttsdteewenmIenintrrl6eiepuirvesuehrtebettfnseEhemalokowrtne0etinlatiautrgopolrlstiaclhle2drshoytrbt1she/ependbncnGcalclosecfihn0onuiaeosyedeuea0neo,ireynclaaatntueawftr11tcnroalsimeiwrsdEtaiw6lbrrlgcoroo.lclgrfi.liel7slihnnaasvbrasugig0toniogsmapmIptthtwpeteisynfeoecciegncdierueihurelgrwtthpceurrheTosnrcahwBstaihiohbdpddpiqirsortdiileooheextsNnsressttictrwciphdsesaeediliuEflmeonIpryin,antetetnypaemm,saowinledd5erorinihoouiuoergoxomlispRdtscoo,lfasoeteiontunfirfrlleaetsorirthnmtpasihtadtlodsitcmatsaGobciuotutmttrlrwi.Mfcdnphlfhpeyiussnew,inluihoisrlaivlrtauiorrtrnayooayfgoe,g,e-rciomedthuolloaohbtbrnabeTnliiepWoeudtmfrncihdrhrwe.fmedInzonmdrheaisaaoecscgwapwochshMfnbslkreJta-bwofrlenfdenatceniokeiteletu1deoeTRfirifhpAentnyowiosaldsgobcscrn.nsereoiahie,cptptesrkhou1vegirdmh2ooyttemeehhc(ntejdcdneisnuocgeakcJeciteerae-aeHc,,spstnaietritrnohestac4sgxuoncrsRfispaslsesoinnhb.raesmlhG.ooiAhay,frc2onhr,nI,ctit,decrdihnfilgoh5teonolneonuonlaisldnsetnzdefefo(ASaecod1tsteu,ynTeolnuhnnfuuetrpisstaas-rieaicnoo7teoavuinhnwoohDtfnocsteemftrtdstgsn4nhxthrwdnfsgergesb:iecermareevvhtslctignhooKisewepseetlehccisirasase6kldtoocneiertnhaccosrdfmboiis3ttodeieitnsehwKv0ac.oawnprrmef'oenfnthr,lho1:reuqaeecit2odeesruarernctnt,lhtsciashehontbuphkhewIro,wnsefblhcotoeodewe,aNaic4rsionstaefiAosm.aeleposoactrndenmobodotdl'ont,hoeki,,liailncnirsiohshiaesap5scaegtcnliicemnadiresolSrueptihssnicictu4mcrec-tlelommhtwatyfuewinsonu,nushsatkhsaiienphilburorpgbif'sreond.sopsrysipryeiafconeidosroel.ewariiferolelutemilaobfl'ceuoetcxnoiteepAdirrl,nrodrdaeedhnPifstrreenol.eoihsiksedcmadeItlrpc.hoyn.msprsuttntcUzs.noo4rdomglxtmeh.eiho'tpl,2eesi.oo.oetogfinghiIbadc.|isoridHtfinrue,>ia.anr.nmsnrmsnttfwis.oig4ryneotelsaeone.ohhrnrnene.tshalHeg.uoson,.fttr.sseiufoaageplprceuaf5c.dwiaesaonewltrie.nnle'fi,)ssgrrrHnso.ihlhtnn,er,eotitll.vgte.toeivasstin-t.Hhlshmuyoomhcoeceelxilsiopn,te,acouttimieissoHolareeenclrehhnTac)t,swrnahnfmorpu.riekwifiu,whs.socerntectgma2drxadwhsantduseoeraodsptllIohpdahwmSet,tte(ienoiregodaarfmn4r)birhetcnwnlotirefnseofsdytrefkallhoeboaciabb,nuhpPaehedineoocvotnl5gopdehndecrolytuldierirlaoenaousewItnlt-oiecroirrricegdl1uuxhnrilhstcnyngnfstsookeldvaptand1oldrrgcdroeotcpyeetchhfgssctxireolhascinrwetNvaarfctwr,rwuisocesiehriaeoapri>ecocoskfnsmhceniiodHosilschpaairvmotinbhmnorawihcooremldea,orldsnneiraiseslohttleeryorsaoonaesesinriorsouiiotcduelhltipatmeeeroakigrnntsemsnowxeb,rtghrtocptycsliuaoorsnvhsittndhidesegoogeoycHatbaerhihnsehprbfwaoalrmehwrdpdlarRttsfbetaeyyolsldshisaumwldiiicsfchusotielttfcmn.kaoreo.hmfeeoldrsd'rrieecpniappeceriaXkivninisngniiiglritlntTbnnoertenoknnouiccrnsrnbtlseicao,hroCKeoopetnichhwfnmhaotearerselrsrobveeadsawl7peaadooetlle2o/.lfeitecsinefMoloeeepeWru,ilffuxur1bsinnosgsoeapialbdruidttnatlrr7tsfpwncpperlginfcciecinmaekyoooa8Aeiidmgivdctootpogaansrhitgiofdrenppipcofsoideoiunnecicuiis.setteeoiaofistinagflntWeehhriissytfaetuertnasnaaxponneotlektirnfaidsreeedscddsluwslsvoactoltnlesncwtegaageinnhtstmser,uhtcrelecnrothhantrntheselbbhoioosoooaay)bnomisiusctsssuivcnseeddto-ddnnyyftof,-esslltf,,f.,,t1i, SOME CLINICAL OBSERVATIONS admpttfohotuatueOrteemhhsnfcopeettulaniotdoolhlt,agtinehteirficenoi3ar5stan1slsir,tdeyuwdfoeoveinngoslsalirtrsovutskohwoere-ebnfnvreasdoifntt,iagebnoccereebfetisyn,trtth.thheieavesiaDnsepctdeenatHetcbelarila,laaimaeblmlr.scligiylhnbieTotrau,yoioftnriingal-otiahnctdcunheoendeonvmi,effeecospulhtomroaraempnocbeomcymklsui,stepsuphn9asuaeettctbtsdiaueoo|orilrvnoefanceacr.olitsatmhtwhNlieeleplyexull,aspmamkkroieennimasncrteulosenasruisrercvksa,oihonnnocodtdgdfhoniimetsmdtipshoea,seednmybdfosceoianhiclrngeoeeaingges-lpatlaa1cnOidnulgnrg tthIhneainrthke*rescoaomrredestidmnuenesd lteoonthgtethhrey dcoIllcionurimicifaeslnctre*ixioausmt*icnmnasitcrihonndfsist.podscarl, Canlidemalslscohento rIntdhueisrtriuendfeorr- DOW1 1 3 0 2 S S L 243 . -sbtggntdgwaGdnsffStwioiaieooeeruroeeoUdrRogieetvTcvrnnIAdsstntiersNynekhehIitodeihksssgMtttirlo,nDehethsaicoanedhnrcuhtdoleeytMlpKarhseseeegn-,frsooysmtsebmrRpeditEvctcttasortftheawcMahrehpRohotnn(nfietuairaelowerBbiidoo,nsamAetbrteestnerchlsrKnlehnXmldena,ces"eotewtTdhceucnNttsfscaccshaccaToirh,opbhydhlgrknr.efilMyiior)e.imcltthno,ndink.hohfd(eefsirApe1hAeracilihHn.soynstmirsta0raaNwchn(ton,sneKdcclNc5FniaaemsNknciedkla0Renntouiwu.lcpeabs,k")lgayfrmeXpciicd)ohoea.snc.T.aansfoceHaufgtHrtrpfheoseutrnnits,eAuhEr-hootelsOr,dnshhlelertouetnIiliuphaLnhtektcMnwsaoehhldhdie"sleTfwltflsesoektpnltEbZh,slcruaiseeiIoseooaRnnsMnrnasgcsrorxrflpylnmpektelhmdetwApsmosmastoI,ense(yehxadcenhNte1pctfamnesuerieaiddc8otsceNitnpconpoioin,i0iparonchl|mmttnsa,m>mnes9ttireteitodgc,cd,dl)esaoifsaeaymiarea,ojTpndsItlounsrnoalewhs.,hEpybelncrtnb,"ictsiraeoLlectcceodptene,hblhrmyueeIEcafhpyeeenanrleIttrasKphlcitVnhfhtocdotuavroleaiggieY.eneefefmbcisecmresentgde,oust,eendotipiisBseclhlobnop.ercyayaqoReenengngruaamrtHucnasiislAsneeovy.lcjeoehptEslddunnUumihsxyftatnRnArteo,tlrcaoNelseogtorcmoyZkcsnhp,smnltnt,to,BeiasthgticvhtcbahtatccElebshecdihaeytyneo|htroyieh>ReteiIdtceelsenecsimslGscnsedssccssdekhutx,rolrs,o,viAnaioripoasoctnsasepcrlmh.enoffcmltoisrktyoaenBdsunisaapersoepRgorlRteccieodtrnroicgoaIclehdAcf,eoo,ipSamardeiasptstUmufsrSetcthtteretttehhehlnkNEholyeaIesnaseydenes,esrr.,-r, TABLE OF FINDIKOS .'^t..'u-rdbcpaofhauiocpEgiarlwfTeoir(ranoonallenonorrleylaibpdEfcebhmthmuedSIgnNtftNnumTcpttApsshoupienGotheeisagsdaks.enetogleeehcehoahcrlensrtriooininsidlurdrnhrreenugoeemtudtnuna=mflittave,vidcoraolaeoicgeeireraoseoonnwamrnnoheieletgndsc;fhpctnnesuetudiaae-.fsca;osietRoniinteasnesconsis;lctaovohsn;iunotrhti,cotaetIaind,drennenomdtrhnsngrdrtlodhisiolscomtejsm,yirleciciehluyereertnreere1ddppvnsctotiougtssmemysgxmianvre;thoth*ha-ecfnauetleadelp.atcdeEneioueawoohtrmoe,saeninrnmnintlma;cmMdcsrvefnrswsii;retc,oUeslseyvotonfdn.eetirccroyer.--e:psaiaorGempibunra.--ahawatgkt;ettnstmuncthnlassiihltiusaeeensNLo=sesoflei.ctePbdepinepmdniror.hlmrnncsronnceesieksseeemodds.dnooona=sdyciofueyocpdopeyneasllsnogiovspeinfTrcrornrenrencmatrofdolenmee;cheargsggsthhlceoaluoetpflimsraort,mr,nlo.hisyoeortbfrob*frmysyaocprintrfpeettgaagnierlornaakerishhoqcyntaitieatnfittortlteconeenohcotecielesenhutnutatpttrnmeedd;hieualdei,;nrumsmeeripcxorbtu.ndlorlrrs;eptrsemae:engeealirpapte;iitc:phnseosleithonalitpamdvlorotMfieo;prisacyadv,titeoengeraeetoen,rinnpanei)sDeeeerrncctdiieluonu.telctdpsenecioonn:fsaroxpaetognsrmie.iaidgepuccitnaecuupcnvrusu;cmsalaayymsulmgeaiituns:ed=in;lennnsbas;d,oitlylcarcicdeemoucttaadacwnDiuueensienpmiiadnptlrriosgbtdanasswpeiediditeisihaeyamfttstnlaaaetsapeciuiverhehresio,cnttostnsi(sfreaefeispre.yhehnnulertfnfdiatbssitsrurenebomeeaefatranatteAiea;ocoishnreueilaloohssttlssbongipktfiresehaaerfriea;luocwmogvculliuorlo;leccs(lsnyaaeneieiweteltticceliio;lactshscidnshomssgamesiaaacetmaiempctieoasme;saeioplkurdslahyroeiptmnino,tinppa)ensiozutkanplaaognnsnlmdryatah;rleaxgfnanlaticcnaniaoloiascsteciletggetayvh.iiiaisuvmsciayiwoihsanotnsleernotaefetnerersi.ecusddersnf)t)ponbeeitsgro.ddois.el.n;iiaa.asfIclidroaI;xvnchdcnf,oianknoncPcatneidmh=oyt(ptctingjfrllleononhedivueaeosyclpheedt.eoeonrgateerssuiispiesidannaocagrcnt;nssnbrsir2Ondmeytienisgsddeoiedwmant.dipp;t;esnmixosyIatnllaioaieseansriltuanfntc:agiythgetfegr(elecrtsldnotuiltpigxeaveneenactatiewdwettr0ho;eotascsedouashptesbfriaslneabkteennotifreslraeaatesbnr,cateiteittstfmsacsinignleolauitrlttsooctfgditiwiecwsaairhceirttteatottaonmieeghhhselosnyybylbtclasnord)s;y;sy;;;seeefad;;eess;.,., eellee1ccOttrrouo-r-eantihycoaongprkliasnplhnalrcctr*nIpdnhuvlecesttoiignavDteioosr.tn.igH.atri.onItsO, CaInlNd IKto anDdr. DPr.UTFtFnSCaTndTARDTr. foRrUcEoDnAduSctifnogr tthhee 16092^5 / vi.. DOW 1 130289 244 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Linn Jones, M.D. and H elen K rizek, Ph.D. ccaccadeitwckhhipwmtw((zzheoohriai71esenaatearichoieamnpnlvvh.lF,o)ttcdthoiaimthh.setieewucnoee2knoariorbhmcnderliaW,cn)inelanubiebhca.oa,ttinrsmhiaatecettniaclotiwtaae0stwtapmAuseanteehantinns.sirslnhics0mgadstino,adtceoct5eslabtrdoacipahermf%htedIufahnilosdteetnhecotoaeipc-lhdpsresnopeywolr0cddeowetvrrmcmhorp.doiuacee0gocreafhemseodbncevepl0yfscrftnkioroedoduopomeobs1cpnskiyprmirsncsunouht%ioetele,esp.tseay.nrns,usnprdat,fdtAwtnsaedecoautrhsatwtdotaieedaubifoohadoenrolfrrcttnahulteilysdeifuugetihssdcvilinoaIiracddtehnsatnnsepihpedeltdroiubnwpeyihidtapfhoenancossextflecleoarrheeytirypitcsensvaqccswigeoihochnnhnttephpnusirssioalcsgitnhuoiagsaupoehisnishmit,vetnrntfrormoetet(yafntleeiikrtsat2olynhancriooeoupendrtcr)caeamnoletagfxo.oceyecleottfftsteihepowre,tiepmicicdEeltovedvntsroiasaniitrhrsteeaxtoneteelhfnihiaechsratznnpmndetayeennpoetmefttefaumlronchaefdeirepipsoeaetndsiuneia2aaxoothxamhflaistnblr,tpubttita3eoitiuircihnueeouanhpylo,lafaire7actnrilnnrtyrhncebitersot,leattnypnas8etestbashdmnaba.hgesed;-nlooiiuiityngersteoamefnTf(cntbeeeststthreohrelernmeft.ta,oaaaeetgauhefea-rlhiptescct.nsiairadnesrhshnireacpoheetnatiiaeHtdeelclmecvnanosbdsboqrousnnegoncaysirbenfcvucrrldactnlotcaoneiieeeaouoeahluddntois,ntdtdnrwundelphiiguneeuctbnlriiwaoeachodtkfaetaeereatahyhoxryrenseretinmindooyr,bprlndzomdcaltaainpfeceaooih-hg1fohscntoaernc-fsai0rerlwknptlpgrhu,nerovuse1ikaire-egmvae|tered4oa>dearisgrihiaao)ildaoipnpcrnga(tsl.erioantuui1ruyodughaciesomnxutonc-tsnthaWittiesei7nedeeseeunbseslniwiist.ddyddrg)nyneesess-s,,, experim ental aaapttmtihonpflluieetPpSdcegtlerrhcrigf1eoveoei0ilgewrdnmi.snr0mgoatnptxtmmimohoswntueiseauachnrptrtrd.ehdwuyoirllergoSeaawertgat|sin,tirrsacoiaocsncwn(b0shi.0nss.hbao.0t3lpii,sw2ltaepe'oesnemnl,mffirdfeeimeiontcdcharhssrratoretiotlusogetgtwdhigmornieoanralenmoavnmsdelbgee.osrs,mib)wceiscatbaeusafdoyrsrouebtfrwsoasgedfecterwdooreoreveshsandaoesiccotifu;hishsoottioenrhnbodbioesfbsnaeieuflnctrdyrohtvadvdereraiaisscttbie,itiraxoholnate1neebncwd,hbmeldifeiatlfdqotr.seheous,caeamsitacde.tuneilsneAtdl0euoevi.dcmn3vne.1cieleaofslmoSlm,rsdreooilemcvif.flnxoreulaogcln1ytlclgie.iyo0ecprd,,tnonutoavml30nyaoei..ne30ssrrf aCzSuuuhdaTPtritcgrhoFWaeehilgrossnyoioenctmnhvrUet,.1es("n7IdetI.ienhamtuceerIa.ecdpl.trlhrSinoCnSetlvoh.wlctdeinetnseidtDo.sncTncaeZoswpiu.poaPep.frIun"ptIbmItoDy.l,rie-ecttnJerhumtdiHnradeoebtofay2llAto0thtng,hhnyee1.u.S0aRe0ADlr2evr.esiMinecpevnae.rerctMtmhiunenegdandincteodarfloDTfCTheMnrveaneeiilnSdroiaiopncrcmigtnieeetn,GNytorUfa.DonniritDvviIAesNnrio-osv4.ineta.ys2-t0OAigo0f-faf,7irt>c-iCeMv2h0eoiU:ciffDa-CgHtehlor)eI-.. m i i329 f 16098v 1753 - C 3-0 ) THE DOW CHEMICAL COMPANY MIDLAND February 22, 1965 - y "EXCITER" PROBLEM, MEETING - FEBRUARY 18, 1965 Present : V . K . Rowe W. P. Falsey K. C. Barrons W. L. Corbin R. C. Hoff H. R. Hoyle D. E. Pletcher W. M. Gill L. Silverstein C. E. Otis G . E. Lynn F. C. Amstutz E. C. Staehling O CO CO Cv cc: J. D. Doedens Otis introduced the meeting by indicating that recent information indicates "Exciter" components may be present in Dow 2.4.5-trichlorophenol'. Bioproducts is concerned about 2,4,5-T acid, esters, formulations, silvex, ronnel, and Erbon. This meeting is to review status of our knowledge of this subject, potential hazards, possible effect on Dow image, legal implications, and need for possible quarantine. These basic decisions are to be made without consideration of economic impact. Summarizing past experiences, V. K. Rowe said that Dow had no chloracne problems related to trichlorophenol production for 25 years until process changes were effected in the spring of 1964. Based on research information accumulated over the years, some ideas have been put together regarding the likely compounds which give rise to this problem. The 2,3,5,8tetrqchlorodibenzodioxin has been pretty well established as a possible contaminant. Also, there is some indication of the possible presence of the 2,3,7,9 derivative and two other components designated as "Unknown No. 1" and "Unknown No. 2". Hoyle said that the rabbit test will detect 4 ppb of the 2,3,7,8-dioxin. VPC will detect 0.2-0.5 ppm of the 2,3,7,8dioxin in trichlorophenol. Also, VPC will detect about 5.0 ppm of the 2,3,7,8-dioxin in 2,4,5-T acid. (By phone on Feb.19', 1965, Hoyle indicated to the writer that it is now felt that VCP will detect 1.0 ppm.) In samples checked from October, 1964, to the present, no dioxin was found in trichlorophenol samples from 349 bldg, using the animal test. The animal test has indicated some activity in one sample of a filter cake which represented impurities removed in T-acid processing. 2,^ "f- *i % ~-y a--7" -2 - DOW J 129845 9 -' Setting of limitsof analytical methods and correlation of VPC and arjimal test data are not complete. Eighteen applications at 4 ppb in TCP represents the threshold for animal reaction. Ten exposures a t *0.5 ppm in TCP gives a mild reaction. A*. * One exposure at 40 ppm in TCP gave a positive reaction. It is encouraging to note that exacting tests have indicated no evidence of-liver damage in exposed operators. It was agreed that Rowe should move ahead with contact with U.S. Public Health Service and Department of Agriculture repre sentatives as-soon as our scientific data is better correlated. Full cooperation'will be offered as regards analytical, testing, and toxicological^information. Process details are not to be revealed. Also,^contacts are to be made with other companies who manufacture trichlorophenol, namely, Diamond, Monsanto, Hercules,-and Hooker. Rowe planned to contact his counterpart in Monsanto' bn February 19, 1965. Where he does not have established contacts, he will suggest that Lew Corbin take care of discussions. Thompson-Hayward do not make trichloro- phenol but are aware of and have been in discussion with Dow on this problem. - - It.,was. agreed that V. K. Rowe should serve as Dow contact for any inquiries'which come to anyone in Dow regarding the "Exciter" problem. Also,-Rowe is to serve as a focal point and advise regarding possible hazards which may result from the sale of trichlorophenol derived bioproducts until this situation is fully resolved. Staehling summarized analytical data on process samples of trichlorophenol as follows: 0 J.O Date Unknown No. 1 2,3,7,9 Dioxin 2,3,7,8 Dioxin Unknown No. 2 Calc'd Dioxin , 1963: June O c t .. <1 3 <1 <0.5 <1 <0.5 6 14 e 17 1964: Feb. June Sept. Nov. Dec. 2 3 253 -3 - 1965: Jan. 7 Feb.8 F e b . 15 8 IOC 3 <1 <1 <1 <0.5 <0.5 <0.5 <0.5 <1.0 - <1 <1 0.8 <0.5 0.8 <0.5 <1 2 4 20 5 3 9 20 10 4 7 45 8 6 17 30 13 BOW 1.129845 -3 - Staehling indicated that there was some evidence that through a process change he could come up with trichlorophenol showing less than 1 ppm of "Unknown No. 1", each of the dioxins, and "Unknown No. 2". * After considerable discussion it was agreed to set a specification of trichlorophenol for bioproducts use to include the designation that none of the dioxins should be present within a sensitivity of 1 ppm and that the specification for the two "Unknowns" should be 10 ppm maximum. This specification should continue until suitable correlation between bio-assay and analytical data are shown to warrant changing the specifications. Ronnel made from trichlorophenol (sample, 2-8-65) (30 ppm of No'. 1 plus No. 2) will be quarantined .unless the bio assay is negative. It was agreed not to use the 2-15 sample of trichlorophenol (13 ppm) for ronriel manufacture. A pre-shipment sample of Monsanto T-acid showed 10 ppm of the 2,3,7,8-dioxin. Analytical data will be obtained on the shipment received and compared with Dow reference samples before a decision is made whether to use or return the T-acid. (NOTE: Hoyle indicated; on Feb. 19, 1965, that this shipment showed 3 to 7 ppm of the dioxin. It was agreed to meet Feb. 22, 1965, to decide on the disposition of the Monsanto T-acid. D. E. PIetcher Bioproducts Department DEP/mm L 16101' 1756 TC- t) T& y-LcuJjLj (J& -ryw yt -^22c /^C jp& Y^ f> . ?3> f w . DOW 1^29422 Of TCDD. TCDD has been recognized as a contaminant of commercial preparations of 2,4,5-T for several years; however, there has been no extensive study of its toxicity. According to Johnson!!/ the acute LDjq for TCDD is 0.022-0.045 mg/kg in the rat and 0.0006-.mg/kg \n -`?" O' the guinea pig. Because of the high potency`of this compound in the guinea pig, these experiments vcrc repeated and confirmed by 16102 DOW 1 129423 -34- Dow Chemical Co. Some information on the toxicity of TCDD is available from a study of TCDD teratogenic effect in the rat (see Section II B, p. 44). No evidence of clinical effect on the dams was found at doses of 0. 0005 mg/kg/day, although embryotoxicity appeared in litters of females given 0.000125 mg/kg/day. Some vaginal hemorrhage was caused by 0.002 mg/kg/day and 0.003 mg/kg/day caused pallor and debilitation. As far as occupational exposure is concerned, it is clear that any danger of 2,4,5-T formulations resides in their TCDD content. The primary manifestation of industrial TCDD intoxication is chloracne, an easily detected, in fact highly disfiguring, dermatitis. It is significant that this condition has not been a problem in factories producing 2,4,5-T with a low content of TCDD, nor among persons who apply the herbicide as . i . a part of their regular occupation. It is,therefore highly unlikely that exposure to traces of TCDD will have any effect on persons who use 2,4,5-T formulations occasionally or who merely encounter possible traces of it in the environment. Data are too limited for a firm conclusion but there Is no evidence to suggest that TCDD as a contaminant In 2,4,5-T is likely to be encountered by animal or man in sufficient dosage to cause toxic reactions. __ References Cited in Section II A 1. Drill, V. A. and T. Jliratzka, 1953. Toxicity of 2,4-dichlorophenoxy- acctic acid and'2,4,5-trichlorophenoxyacetic acid. A Report on * \ - ** ... Their Acute and Chronic Toxicity in Dogs. AMA Arch. Industt~Hyg. Occup. 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'< i>u* y /s /0/ 2/ 3 ,4 fc'T ** iA t\s lOfol IA BT , H *1 JflA U S u jA**dert rdz5 - T"* icf^y S.'L^\s?'x-' St * > fa \ 1 ,"7 ^ *****as 4*-4 I X-^<**JL ix^ **** ' (/*? /K & \ s#*L ' &T 'if Z JtA * >-rl&Tsr*U!jj?' e r Bt signed ,, R a s c i a - 3. D a te // i d h 16111-- o oo o V- ri O-O* 766327 '-Y -T 'W T T ' ^ ^ 'T sirz r^ iD d i r - 'rz *jjQ 1 - qh r-ov S O 7 COS Animai r? - ani Ca^c # G-SV O r i, 0 /t .o d>-l UUllttii ->t- <Ly ,T //j &C^>J1-L`{T ' C L st^ < - e n d DOW 766328 f jsd $JL/L$ l^f^-7/ie>(a g a t^ u . (mJ . O SZ c r no -7 C / a /t,/7 =^Af" .7 *T g n _ o # % - __________________ /L sC<s < >/ ^ K ^ u W s ^ (o -r z jd ? no - 2 z th ni lT T toI H 0.9 .il .yus<- UcSj 6T to fei 3 <**T'- i m 8T ,. /o/a-ar jW //A cr iQ - '/ /e/? X UT LW CT* 0 i teff L\<f io14 0,9 S.U )p. i&t&l a-? , . 4 . :<**'** Q i h , L A A -te^ V L < JL ^ > - G 7" ^-7-- d *-7 /7 * j^/st< r^C ^i>a > fol>4 o .q & 'a*'=[. .itih -\ ^-- d; /0/j3/ /. 8T" )* H * ~ $ `4 f c ' X - , /o i J h * J ///a/^C., S d * . B_r ET U i^ned js U h '^ e -C s 'J H u i , Date //,i i k 16114 rc o D O W 766330 V jn <o $ N \\ \_n ,\ ^ \ ^ sc- ~cT \\ *0 V SV-L-^---\- - --- ;--_ A > >>?.? \ \^ VV \ ^ \ ~ "ctr" \j^ V ^ 3 <0<S)QV,,S iS l - d ^T-7 a ^ TO O r> v Q vi <1 ' V , >> ns - $Z > 9 <JD i H CP tt4 ii I i - ii - 1866 3^9 BUILDINQ D O W 757H2 Sodium trichlorophenate from 199 Building ia received - b y ^ 3^9 Building where it ia neutralized^ which affreebg a ten-fold con centration of the material to provide crude trichlorophenol. .'hlj "wet feed" i3 jMMkt through a drying column; the "dry oil" i . tnen distilled in two color stills. The first animal testa run on 349ysamples in 1957 indicated activity only in the tar from the color stills.. This was mild activity, less than that demonstrated by the caustic Insoluble oil at 199 Building Similar samples taken in early 1964 again showed the tar from the :COlor stills to be active. Samples taken in October 1964 showed activity in the wet feed,rthe dry oil and again^the tar from the color stills. The product was still not active.on a n i m a l s S a m p l e s taken in November 1964 showed activity again in the wet feed/7\thhte dry oil and the product a inactive. The degree of activity in the crude material,^ was less than that in the October samples. JL. The contaminated phenate mentio n e d abevc-r at the end of ft. October 1 964/^was processed by 3^9 Building, ttic -acti vities' pipe fitters and an operator at 349 in early Novembeiyinvolved cleaning* J ^^ lines and changxa^- valves in lines which had carried the contaminated phenate. The actual exposure that brought on chloracne in the 349 Building personnel .is not definitely established but this is the most likely situation which could have caused it. In early November'; Clare Bailey, 349 Building^uperintsndent, issued a written sheet describing precautions to be taken: because of the - 12 DOW p o te n tia l hazard. T h is re su lte d from tne 199 experience and was promulgated on E a l l e y ' s I n i t i a t i v e as a p recau tio n ary measure. About the f i r s t of t h is y e a r, 1 9 6 5 , o b je ctio n s by workmen to working in 349 caused the adoption of f u ll - s c a le p ro te ctiv e measures in that b u ild in g in regard to the trich lo ro p h en o l p ro cess. Fu rth er complaints caused the extension of such p re ca u tio n s to the e n t ir e re a c to r room, in clu d in g the bisphenol p ro ce ss. Wipe t e s t s e v e n tu a lly in d ica te d th at the p'UUH- bisphenol ie *fre e of contamination. In f a c t , only lim ited areas of the trich lo ro p h e n o l s e c tio n show contam ination. Clean-up and f u r th e r wipe t e s t s are being delayed u n t il p ro cess equipment has been moved to a new lo c a tio n o u tsid e the work area of 3^9 B u ild in g . Exte n siv e clean -uj w i l l be necessary in the alleyw ay behind 3**9 because of contam ination from the trich lo ro p h e n o l t a r . A h e a lth s u p e rv iso r i s now sta tio n e d a t 3**9 B u ild in g and f u l l precautions, a re being taken on any Jobs where exposure i s p o s s ib le . Onl; J -3 Jf three cakes have shown up a t 3**9 thus f a r , none sin c e the in cid e n t In *o e a rly November. Composite samples of fin is h e d trich lo ro p h e n o l from 3**9 have been run on anim als at e it h e r a 10^ or lj6 co n ce n tratio n in Dowanol.HM. Under these c o n d itio n s , no fin is h e d product from 3**9 has 3;hrot wn a c t i v i t y j on an im a ls. Quite r e c e n t ly , VPC has succeeded in lowering s e n s it iv it y V ef f o * r TCBD in tric h lo ro p h e n o l to about 1 D D m . They have sin ce analyzed\ some r e t a in e r samples and ' found , + 4* p lus unknowns that appear in the same p lace as the c h lo rin a te d benzofurai These samples were extracted with chloroform for analysis. The chlorofo. extracts, wtaerT'placed on r a b b i t s 1e a r s , are s h ow i n g activity. 16118 1874 IN D U STRIA L TO X ICO LO G Y LA BO R A TO RIES / c* VgAGRCtN 4 * 0 4 3 0 / '/'Si //J 77 *' V FO R M ER LY M YTH LA B O R A TO R IES INDUSTRIAL TOXICOLOGY. IN W IT ltA T IO N O p PUBLIC HEALTH. INDUSTRIAL HEALTH. AHO BACTERIOLOGICAL PBOBLEMB. CLINICAL AND LABORATORY mVEETiaATlOM E O P PHARMACEUTICAL PRODUCT. 34TH STREET BELOW CHESTNUT STREET PHILADELPHIA 4. PA. i H EN R Y F IE L D SM Y TH . M.D.. D r. P H. CONSULTANT JO S EP H STAMRUL, M .D. INTERKIST JO SEPH V. KLA UO ER. M O. d erm a to lo b ist J E P F E R S O N H. C L A R K . M.O. PATHOLOaiST HERM AN A. S H E LA N S K I. PH. O. ro iico Lo aisT HERM AN A. S H E L A N S K I DIRECTOR 1 June 6, 1950 Ur. V. K. Rons The Do Chemical Company Midland, u iohigan Dear Ur , R0we 05 OJ CA I wish to submit the following report on the patch test study made with the materials listed below. 1. 2,4-Dichlorophenoxyaoetic acid (Sample # 1 ) 2. 2,4-Dichlorophenoxyacetic acid (Sample # 2 ) 3. 2,4-Dichloroph-noxyacetic acid Mixed alkanol amine salts. 4. Mono Di, and Tripropylene glycol Butyl Ether (B) 24-Dichlorophenoxyacetata. 5. TCX No. 9 Esteron 44 6. TCX No. 10 Esteron 2457 7. 2,3,4,6-Tetrachlorophenol Sodium Salt. 8. X-Bromo-p-nitroacetophenone 200 unselected human subjects (100 males and 100 females) were studied. The material to be tested was placed in contact with the skin of the back and al lowed to remain for a period of 5 days* At the end of this time the patches were removed and the reactions noted. Three weeks after removal of the first series of patches the material wae again applied to the backs of the same sub jects and allowed to remain in oontact with the skin for a period of 48 hours. At the end of this time the patches were reaoved and the reactions noted. The results obtained a r e a s follows* i 1 2.4-Dichlorophenoxvacetic acid (Sample #l) - 100^ sb supplied First Application 1 male had a 1* reaction 99 males had no reaction. None of the females showed an/ reaction. Second Application None of the m&lea and none of the females showed any reaction. 2 24-Dichlarophenoxyacetic acid (Sample ,t 2 ) - 100^ as supplied First Application - 16118 i ?+ "actions. 85 males had no reaction. [ *dr. V. K. Rowe -2 June 26, 1950 Second Application None of the males and none of the females had any reactions. 3. 24-Dichlorophenoxvacetic acid Mixed alkanol amine salts - 10^ aqueous First Application 3 maleshaA a 1* reaction, 1 males had a 2* reaction* 96 males had no reaction. 2 females had 2+ reactions* 98 females had no reaotion. Second Application 1 male had 2+ reaction* 99 males had no reactions. None of the females had any reactions. t 4 Mono. Dl and Tripropylene glycol Butyl Ether (B) 2,4-Dichlorophenoxyacetate - 100% as supplied First Application None of the females and none of the alee had any reactions. Second Application None of the males and none of the females had any reactions. BOW 75563G 5. TCX No, 9 Esteron 44 - 100# as supplied First Application None of the males and none'of the females had any reactions. Second Application None of the males and none of the females had any reactions. 6 TCX No.10, Sstaron 245T - 100^ as supplied First Application None of the rales and none of the females had any reactions. Second Application None of the males and none of the females had any reactions. 7. 2,3,4,6-Tetrachlorophenol, Sodium Salt - 1j, aqueous First Application - 3 males had 1+ reactions, 2 males had 2+ reactions. 95 males had no reactions. 5 females had 1+ reactions, 2 females had 2* reactions. 93 females had no reactions. Second Application - None of the males or females hd any reactions. P. a-Bromo-p-nitroacetdphenone First Application - Butyl Carbitol Acetate O / None of the males and none of the females had any reactions. Second Application - 1j. Butyl Carbitol Acetate 2 males had 1+ reactions. 96 males had no reactii 2 females had 1+ reactions. 98 females had no rei From the above information, it appears that substances 1, 4, 5, 6, and 8 do not arpeur to be primary irritants. Substancsi 2, 3, gnd 7 have mild primary irritant action if^ kept in contact with the Bkin for a prolonged period of time. None of these materials 16120 i V. K. Rowe 3-- June 26, 1950 tsr.d to appear to be sensitizara* Or* Kluuder'a report will follow ours. If thore is any further information which we can supply, please do not hesitate to call upon us. Very truly yours, INDUSTRIAL TOXICOLOGY LABORATORIES He_ Director e95$$ MOO 1G12 ;f ' ' 1876 LJioveicter 2,1(>'<2 Mi*. Goorco v:. CullInn . resident Claim fLina?:r Lcploycro 1717 boot DKuidtufacluallodflnWcausa.u 1717 Wcot laid Avenue Haohvilla 3, Tenneaoco ' ' -::^V CM Noi 2 Dear Hr. Rillir.ai 'mis 1b In reply to your letter ol* October 26, li>62, asking us for i.hafc irh'urautlcn we cay have relative to the toxicity of 2,4-d and 2,4,j.*! herbicides. The tcnicolcjicsl information vo havo on this type of chealcal lc tmev wall esarlLad in our publication entitled, 'tau .aiv cf Tcnl. clerical'Information on 2,4-D and 2,4,^-T Type ilorblcicin arui un evaluation of tho iiauarda to oivesteik Associ atea with lha-lr L_a''. Thio publication ives the buslo toxic lo:leal li-ormr/eian cn these catcriaio. A copy of this reprint io cr.eloae:.1.. Alta, cLsut 10 ycara ugo, we published an article entitled, "ili-ilta fauat Ja Acecaictcd with cho Handling and Geo of h_:biciC.:3 ,,. thilc thio cicala with materials other than 2,4-D cni 2,4,5-V typo herbicides, you cay find it interesting. A copy of thic ic aleo cr.aleeud. Lccuuco we have received a nue.ber cf quest taco rec*CL:Ji:: the feasible effects of swallowing EuLetur.tiul ua.au.ms cf the material ceeiCentally, we have proparal a cheat iic Lr.j the spratcan, r-ceiLlc effects, and sugr.cstcs treatment far the fcar.a-it ,-of paloan control entera and phyciciune. A c;:p7 cf this io alee c u e m i , but I do not know v.hsU.cr it villi be cf t::y use to ya*a. Is io entitled, '2,4-D and belated Typo Herbie lama, Tencola. '.:ui Information and Susrpctlcaa KoardlL. Tar-tuent fur lea.___ _ e..allcalns 2,4-d and elated Typo iiarblotvl-- Generally speaking, J3,4-D u::i 2,4,5-7 [,___ent very little wizard from tho otaudpDint cl* the user and p._*jv:Ioulljr none to those who eight accidentally to cmsaecd to a c__.ll amount of spray drift. The cluiL3 presented by the lady mentioned in your letter sound to oo to bo propoacerouc. Her difficulty nuct have been oauaed by something entirely unrelated to 2,4-D or 2,4,5-T. now her drinking water supply could have been contaminated to any measurable decree by drift is inconceivable. You ask about our experience with people in the plant who have been handling and making eheue materials for many years, i nave a Ul Cfl CO C5 I I 16122 DOW 755597 'fir. G. tl. fiullins >2 novecbor* 2, 1 $ C 2 cor,suited t i l t h out Koiical Dopartment and they rejail no cases cl* a n y oicnificcnt eystcsio effects. They have, of course, c c z d a n cccccicr.al cues of transitory dermatitis, eye irritation, respiratory irritation duo to dust, ano 1 believe oco case of nausea, tut they ccuLt that this as duo to these materials. This typo of coiparicr.co is typical of most chemical manufactur ing oporotlcoo. I trust this information Mill be helpful to you. ainocroiy yours. V. K. Rrjo Licchcricul iioccarcti Literatory 17 Cl Euildics \~yjd cci C. Q. Kronor, H.D. D. G. Kochlincor V. K. Rowe (2) Tc3.1^-11-20 -- ^ Correspondence 16123 DOW 755593 1877 Dr. V. K. Rows Dow Chemical Company Agricultural Chemicals Dept. Midland, Michigan Address Reply To CMFlflYC MUTUALS O f WAUSAU 1717 WCST CWD SUILSIM8 1717 WCST CMS AVCMUC MAANVIU-C S, TCUSCSSCC SMOMC AlAINK 9-7477 October 26, 1962 CO CM O Dear Dr. Bows: We are the insurers for a misfcer of electric power distributors who use chemical spray for weed and brush control along their right of ways. We are concerned in this particular with the chemical formulation known as 2,/*-D and 2,4,5-T. We have been presented a dain by a lady that some of this cheatcal sprayed along the right of way in the vicinity of her residence found its way into her drinking water supply by sose unexplained mans, presumably by drift, resulting in nausea, bronchitis and defective vision. It is further alleged that die breathed some of the "fumes" from this spray. j We understand that you have research papers on this subject which would be of a great benefit to us in defense of this type of claim, and particularly with reference to workers in seme of your plants tgiere this chemical is made tdio have undergene periodic examinations with no ill effects noted. We would appreciate your kindness in supplying us with Wiatever material you may have on this subject, and any further personal comments you have to cake would be appreciated. Very truly yours, RECEIVED, OCT 3 1 1962 V Biochem. Res. lab. 1612< **4t- 1878 DOW 755561 (larch 31, 1953 o 0C0M K\ rv. O Dear Dr. ICohn This is In is^ply to your letter of torch 24th inquiring ao to whether we huvj any information concerning tho toxicity of 2,4-D to hux:r,o. Insofar as I know there ha3 never been a case of couth or curious illness due to 2,4-E or related products. T..-u- 1.:a o L-cn a few cases of dermatitis alleged to have c-v.r-u L/ this type of material. In each case wuoro a t h a > i i / . ^ i p i g a t i o n has been possible it has been found th_t tl.. c*.-- :.tiw agent was the oils uaod as diluents rathor tlu_n co th,, 2,4-D or 2,4,5-T type materials. This is consistent with the nogotlve recults of sensitization studies conducted cn Luuun subjects with 2#4-D and 2,4,5-T derivatives oomxonly used ao herbicides. I believe tho publication from our laboratory entitled 'fuc- Bfry of fox loolegleal Inforgeation on 2,4-D and 2,4,5-T Type Herbie idea end lci La filiation of the liasa ran to Livestock Associated with Th-it* Use,-11 contains cost of th* pertinent riforonc^a dx.lbhg wuth tho toxicity of these materials. We also puaaor-od on dago and this it reported in an article by L_ ill `Toxicity of 2,4-Dichlcrophenoxy- acctio Acid l.:.w S-vuLclilcrcphcnoxyacotic Acid. A Report on Their Acute uad C.auric Toxicity in Dogs. Reprints of both of these articles are enclosed. Tiic laboratory cxia-wo have obtained together with the very bread experience in t ho uuo of these materials convinces us that they ere axcr.c tho lcaat hazardous of tho chemicals used around the homo or farm. If you have specific questions which you believe we might be able to help you with, please do not hesitate to contact us. Very truly yours, V. K. Ilowe Biochemical Renearoh Laboratory 12-634 Building VKR/ba Snc. 16125 < Affceesa o o w c h c h c o CRANCH SA LES OWPICCS NSi*PALWSWHCONAAHCLSADSBlIlSCEOHNTFEOYHA\VAULRITTOSCOITAERANSTNEARTLLTNONGOGLKGALOOTIECNPTETNOAUNLIHOSOIECINCSASITOY C C V. K. <Ro\!Q W. V.'. Allen Clyde Bryant /T h e D o w C h e m i c a l C o m p a n y M ID LA N D M IC H IG A N July lu, 1931 1834 i__ Mi'. Ciiarlea L. iiovey Eastern States Farmers* Exchange West Springfield, Massachusetts Dear Charlie: Your letter of July 12 to Clyde Bryant has been referred to me. We know of no recent work at Ohio State University which shows that certain crope may .become poisonous when treated with 2,4-D. I believe the report in which you are interested was made by Dr. C. J. Willard of Ohio state University at tne December, 193`~> seventh Annual Meeting of the Northcentral Joed Control Uomerenc in Milwaukee. This paper is found in the proceedings of this oonforenoe, pages 110 through 1 1 2 . I am enclosing, herewith, a copy of the portion of the paper which bears particularly on the problem which you have brought up, al a list of the pertinent references. You are acquainted with Che work undertaken at Michigan state with our various herbicides, which snowed that there is little. If any, danger in grazing treated pasturage. It is quite apparent from the evldeiice to ante, that the Important hazard with regard to the use of nerL-icldea, particularly of the groatn control type, is a possible Indirect effeot as pointed out by Dr. Willard in his article. Since there appears to be same evidence that normally un palatable vegetation may be made attractive to grazing animals by 2,4-D or 2,4,5-T spraya, it would seem logical to keep animals off the treated area for a certain period of time. If the Increased palatablllty is of a temporaly nature and disappears in 72 hours or less, it would be logical to advise keeping stock away from the treated area for three or foui* days after spraying. With brush and trees, the evidence Is as meager as it is with herbaceous, annual or perennial weeds. It may be possible that animals should be kept away from treated brush of certain species for longer than three to four days. In any event, where cherry la present, there la little question but that the safe policy la to advise keeping cattle out of the treated area until the foliage die. 16126 DOW 7 5 5 4 5 2 Hr. Charles L. liovay Ecotorn Statco Fui^ero1 Exchange Paco Two July 18, 1951 As to tho hQccrda Involved in nitrate poisoning, we have little if any movo information than la available in tho excorpt frea tho article by Dr. Willard. It la surprising that there Is so llttlo definite Information to go on, but studies of this sort aro not too easy to undertake. aUp to the prcccnt time, we have not put warning statement on cur labels with regard to keeping livestock away from treated areas. Hcrjovcr, there la a feeling that we may adopt soma sort of a precautionary statement. Sincerely yours, THE DOW CHEMICAL COMPANY Lawrence outhwick Agricultural Chemical Section Technical Service and Development J1 16127  DOW 7 5 5 4 4 3 COPY MISSOURI STATE HIGHWAY DEPARTMENT Jefferson City, Missouri April 2, 1951 1886 COPY o CM z MATERIALS: Handling Herbicides Mr. L. L. Coulter Research and Development Dow Chemical Company.. Midland, Michigan Dear Sir: We have recently received a report from our Workmen's Compensation Department to the effect that one of our maintenance men had a leg infection which was caused by contact with the chemicals used in spraying tree stumps. The chemical used was 2,h,5-T mixed with diesel oil (one pint to five gallons). This is the first report of such injury to come to our attention, and we would like to have your opinion as to the relative possibility of skin irrita tions that might be expected from the ordinary handling of 2,l4-- D, 2,V,5-T and T.C.A. and your suggestions as to safe guards to use in the handling of these chemicals. Very truly yours, (signed) P. V. Reagel Engineer of Materials 16128 1887 Tndlreot Effects of Herbicides C. J. Willard Under "Indirect Effects of Herbicides'1 we hove Included all effects other tnan direct damage to the weeds or cron rlante to which they are polled. The discussion will concern the newer organic herbicides only. This Is an extensive lltreraturo on tr.e effects of sodium chlorate and arsanlcels, which doer not need reviewing here. DOW 7 5 5 4 3 4 The indirect effects we have considered are: 1 , Effects outside the treated field due to drift or vapors of the herbicides, 2 , Unforseen effects on tns "balance of nature", 3* Destruction of wild flowers, ~ame cover, etc,, in roadside arraying, 4, Poisonous effect of herbicides, a. Direct effects b. Poisoning from poisonous plants, not usually eaten, but eaten after spraying, c. Poisoning from ordinarily harmless plants made poisonous by tne effect of sprays on them. 5* Effects on the comcosltlon of crops. The first problem, drift of dust, droplets, or v~oors to adjacent or not-so-adJacent susceptible plants, has been eo widely discussed that I will take time to make Just one point about vsrors. Any effect of vapors must be more or less a mass action effect. Dr, Alban and I have used experimental amounts of esters around Busoertlble plants for years, with no effects on them. But those were small plots. If you Spray 10 acres with esters and wind moves blowly across this area (Have you noticed how almost every atopy of vaoor damage begins "There was hardly any wind*?) the air may easily pick up a toxic load of vapor. As wesd control men, we must constantly emphasise the hatarde Involved In using these extremely Dowerful chemicals, and nereon&lly and by predept, see to 1 r that every precaution Is taker, against damage where no damage la Intended. This oannot be said too often, or made too emphatic. Carelessness In anr>l1 c,'tion has already resulted In some severely restrictive laws, and others will follow If they seem to be needed. Several articles have anpeered expressing the fear that we "weed men" will run wild and exterminate local flora of all kinds 1 n ell plaoes. Killing plants even with modern chemicals, still takes M m e use either awnhdenmaweterdioaln,otwhhia vceh cost money, c.n economic l.'e are not likely to reason for doing so. In so doing we may kill some plants tnr.t we do not intend to >111, simply because they are in bad company. 16129 DOW 7 5 5 4 3 5 <>e snould not be, nor- ./e, n t or oblivious to changes In the balance of n -"<>-e ;id snould study tease chmr-ee and, so far as possible, avoid recommendations that produce un favorable changes, or suggest ways of overcomlnr tnarc, For example, repeated roadside spraying may take out lecrumea end, on many soiig, reaulre nitrogen fertilisation to maintain a healthy sod. The complaint about kill1nf? wild flowers alonpr r-.-as^dcs 1s one to whloh 7-re must, at least partially, plead guilty, _ut -'Itbout apologies. r>oma of these complaints remind me of tne antivivisection rroups throughout the country, to whom, if one were to .ludre by either actions, the liife of a st^av do? ia mors aacrec then' thj lives of children. We will always have some unreasonable complaints, ro for ns in us lies, we should be "wise as serpents and harmless as doves". We should listen to these complaints, "udy them, and then, if the welfrht of evidence is then on the side of weed control, answer them cooperatively and courteously and f?o ahead. Dr, E, P, Sylweater has done this beautifully in hi a roadside spraying crmpaiffn in Iowa. He started trts In cooperation with the Hl?h''ray Derc "tment. In l^U*, The unsightly unremoved, dead bruah along the road started critics talking ao vigorously that the campaign was "soft-pedaled8 in 1*P, resulting in poorer results and gre; tsr expanse for the Highway Department. So, this spring, Dr. Sylvester arranged for a printed debate between himself and one of hie active opponents In the Sunday Das Moinea Register and Tribune, wnlch has a Sunday circulation of nearly half a million. He also defended the roadside spraying program at some 50 meetings throughout the state. As a result, the Iowa road side spraying program Is golns- ahead full steam, with relatively little criticism. His handling of the program was a model of public relations for all of ua. So far as anything I might say here defending roadside spraying is concerned, I could oniy say what Dr. Sylvester sail, or say it lees well. That article has been reprinted several time*, most recently in "Down to Earth1' (Fall, 1 Q 5>0 ). I sup-mest th*t you f?et it. It la a trenchant defense of the beauty, safety, and economy of grasacovered roadsides, produced by spraying, as contrast31 >fi th the mile* of poison ivy, 'lid carrot, brush, hemp, reffweed, etc., etc., which still corstltute rhe average roadside. FolsorUnr by herbicides is r more serious m n ^ t e r . Fortur.r* el;- our r-roblemfi are small comn firei to of the en^onjolmrists, but we definitely do have problems, Tp the first place, any new tr.in? gets blamed for anythlnfr that hpor.ero in its vicinity, ' hen D", ~e~. of our Department made a week*s tnu~ of northwestern Ohio in 1~^7 putting on a few spraying- and dustlnr 1epont"aot1''n3 wi tn 5,*i-D, two reports of nolsonlnp- followed -- hotn Inter soown to he r r m e ou q, but Illustratin' tne tendenev to blame troubles onto ranvthlnr new. Last summer T Investigated a case of allege! sheen ooisonlne: by a 16130 "brush killer" used by an electric coop, Investigation showed that tnero was no reasonable chance that the srraying war. responsible, but the spray truck passed r.lnne: c, Iittl9 before the sheep took sick, so the two things ware linked, both by the farcer arid by the veterinarian Of the new herbicides, TCA is caustic to the skin and the dinltrofl are definitely poitonous The D\!,s are a serious k^zavd to the person applying thee - death has resulted from loner timoaurc; to air contaminated by droplets of DM spray - but eo far no co-.;Lai oz s of livestock poisoning from DN's he ve enee to our attention, and Praz!nr experimentally sprayed areas with them at four tires the recommended doaeo has riven no serious results (). The snr.e is C true of TCA () - 2 755436 There have been a few reports of persons who are allergic to or affected by 2,11-0 There 1 s no reason to suppose that at least some of these reports are not true. These are important to the few individuals concerned, and worthy of serious study, but we nov/ have experience enough to any that they are highly exceptional. To help put the matter in proper perspective, in ray personal experience I know mor people who are poisoned by e^vs than I have definitely heard of being unfavorably affected by 2,^-0, Vany tests (&, 11, 1?) have shown that stock will consume errass sprayed with 2,^-D and ?,b,c.-? readily and without injury under ordinary conditions. There materials have been directly fed to milkcows without injurious effects on the cattle. Host reports also state that there was no effect on the milk - Dr. Grigsby in a letter reporting unpublished work this summer (1 ^50) a a y a that cows fed large quantities of 2,k-D gave- milk with a chsracteri at'n phenol flavor during the feeding and for 12 hours after the 1-at -ose of 2,4-D had been given. These experiments and the experiences of thousands of farmers with sprayed pacturen pretty -rail dispose of direct 2,-'>D toxicity to stock. However, alro'-t mil of us have seen sprayed plants eaten that had not been ester: before -- all the way from 9, M, Haleigh's case of rodents chorning to eat rovrn of corn tr~: tad pre-emergence with 2, fcD to stock Canada thirties (O. -J. ), velvet leaf (J. L. Hutchison), Jlmaon weeds (r . V.'. nii f c ) t wilf parsnip (Geo, Briggs, G, J. v;illc~d.), sunflovorr. (T, F, Yost), docks (Crafts and Harvey), round leaved mallow (N. ^ . Chafer) and unpalatable weeds in general (Chas. J, filbert, H, , W o o d ), Clearly, if any of these vr:.rs were 1nJurous or polypous, their sudden consumption after spraying could cause sickness or death of the stock. Actual instances few but aupr<~Bt iv s . C, J, Gilbert mentions oesea of poisonous range weeds causing death when eaten after arraying, both b>rr-er. Shaw and Oliver Lee report roisoning of cattle from ?,d - D - c r r a y e d . wiId cherry and i f this 16131 -In DOW 755437 definitely polaonoua plant, la present In an area to be sprayed, It would certainly be well to keep stock out of It* J. H, Fleetwood reports herring of a case of awl ne eating arrayed mature cockle-burs with severe sickness following. Grafts and Harvey (4) make a similar report concerning arrayed thistles eaten by lambs, Virgil Freed mentions several instances of ragwort poisoning livestock after being sprayed with 2,U-D, He writes: "Normally, livestock become poisoned on this plant only when they are fnroed to graze 1 t by lack of other vegetation, particularly in the late winter end early soring months. However, 1n the Instances mentioned above, 1 t was a case of the animal actually seeking out this riant two or* three days after unraylw: and consuming sufficient quantltine to he toxlo. Plants that had been treated for a oerlod longer than one to three days did not appear to be palatable to the animal and the Initial palatability was attributed to the marked Increase In sugar that accompanies application of ?,U-D to these plants. Normally the higher sugar content extends from 24 to 7? hours after spraying, thereafter declining steadily." A wise precaution, therefore, would be to keep stock out of sprayed pastures containing any poisonous weeds for 3 ^ days to a week Much the most serious posslole 2,4-D poisoning effect that has been reported was due to the accumulation of nitrates In sugar beet leaves that have been sprayed with sub-lethal amounts of 2,^-D, For these data I am almost sntlrely Indebted to an unpublished naoer submitted tc "Science" by L. M, Stahler and S, Whitehead, which T am abstracting In part. Nitrate poisoning of stock has been known for some time (1, 2, 5 7) especially In connection with oat hay. Beet leaves from a Manitoba field damaged by clrplane spraying of an adjacent wheat field In loll2 caused the dorth of several steers. A local veterinarian recognised the symptoms as those of nitrate poisoning. The standard treatment, Injection with methylene blue, revived living but recumbent steers within an riour. The leaves were analyzed for nitrate and'showed nitrate levels for above those known to be toxic. wereIn August, ld^Q, 'z'r(y acres c f beets on seven fs rre In North Dakota sprayed with lnssol.1 c* le contimi with f, 1-G (lc ). Through the cooperation of Dr, ,Tel~eson and associates, Dr, Stahler obtained samples of b e e t I s ' ves from each field no also from three adjacent untre-t e d f i e l d s . The leirves from u n t r e a t e d fields averaged 0.2? percent fTNOyj the nversge of t h e sever, t r e n d e d fields was k.p percent, h*'0?, with - r,r-nge of l.fl to ?,77 percent. Over 1 . 5 percent of KN03 i n t h e dry m a t t e r of forage 1s csnol toxic. The tonicity of ni tr a - ? i,, not ilr sc', hut In trie yi'-.-n of ruminants, nitrates are roduce.i cr, nt tr1 tea, wr.l cn so >ilter . e blood that. It cannot c; ry oxyver fror,:t:t lur...-, to tr,e t sue,, The blood becomes brown instea d of red, w 1vl n^ a gray-tr r. ap enr.... to the mucous membranes of the noga and mouth, b'nlasa *r e^ te i 6132 I - 5promptly, death may come In a fev hours or less. DOW 7 5 5 4 3 8 Pigweed (Aceranthua ratrof larua) and la.-ioaouartera (Cher.oondlur; cLbua) are coruTon voocie clocely relotccl'To beets w.-.ich Olson ^na br.Ttehead (13) at South Dakota have e-own to accumulate nlt.r: tes In hazardous amounts, even without 2,11-0 treatment a* J. Zahnley writes me of unpublished work by Harold Jones of Kansas State College, showing that lambscjuarters, pigweed, and smartveed (Poly~onur; r c .) treated with 2,^-D were extremely hlrh In nltrats, while troee not treated contained very little. Tills sacred to be due to the 2,1-0 checking the assimilation of nitrates Into protein, so that nitrate accumulated In the treated plant, but wsb used up In the untreated ones* It would surely be risky t.o aoray a pasture containing td *'-= weeds* Presumably, If they are killed outright, they will not accumulate more nitrate before Tenth, but. with the practical Irregu larities In sprsylr.ir we oannot be sure that t-Mn will occur. Corn, sorghum, Droso, sunflower (Hellant bus ar'.) gun-weed (3r1 ndel 1* fon, ) ard eplderwort (Trsdescsntla enr. ) hove also been Indicated TX"T) as containing lethal Quantities of nitrate under some conditions. Mr, C. D. Floyd, State Apiarist for Minnesota, reports one rather oleer eeee of polsonlnr of bees pasturing on mustard apvcyed after it oar,a In bloom. Ha wee not able to dupllo-te the result the next year, even by feeding the beaa syrup contaminated by Bupposedly the earns 2 ,^-D formulftlon used the year before. However, aocr?thlrg killed the bees the preceding yasr Mr, Floyd"eal5'"ho "reports of Injury were received In l^S^* Apparently the trouble Is at le&at unusual. There will be many of'these crobleirs, real and imaginary, at vetd control continues to develop. Cur attitude, as rood voed control men, must be to consider every complaint, even those -r,ich look absurd, cautiously and oarefully, m l then nnyln.r "Impossible" without lnveatlgctlon, or fearfully aoceotlng unproven responsibility. There have been many reports of 2,^-0 Incrorslnr the protein content of grain Co , 1 ^), Ir. jren'"'\-.l, there effects soon phyelologloally to be like the 1 reversed protein obtained In s dry season I that ia, the protein elements In t.hc groin arc laid down first, and If the rrntn does not nroteln then one that, dnea fill, "Uflslu r "l i yv,eila,t it will be least, the higher in p'-oTMr per core her not neon lncronwed by srvrv} r.r. However, r^ny of tl. offset?, on the vegetative parts of plants (1C, '*) are not so slr.vlv e :t r vl le field Is open for* the study of the effects of 2,^-0 t o ' --cl'ind coprounds.on fnrnre. The abatable ren tr,ny veil the -Truster ^*v*lo'->m''nt of fiber ir: rs^.-rat u b , etc,, follow! pc- ?,**-- D tvrr.trents. rr; f1 el i or^rp we have no W s as yat, but the problem lr hlchlv 1 r-o-tent. 16133 - 6- Literature Cited 1, . Blnrcardlbeyy,oatW. B., hay Crpson, H. F. A* and other planta Per.th, 0. A. livestock poison- containing nitrate, Wyoming Ac t , Exp, Station Bui, PUi, lUo. DOW 7 5 5 4 3 9 2, Cook, K, L# The effect of eoll type and fertilisers on nitrate content of tho expressed sop and the total nitrogen content of the tinquee of the snail Kredns. J. Am, aoc. Apron 2 ?: (1 ^30) 3, Corns, W, 0, Effeota of 2,UD and soil nol ature on the ont<-l; e aotlvltv, respiration, and protein content of bean planta. Can. Jor, Pee. g j ^ - l ^ d o ^ O ) k. Crafts, A, 5* end Harvey, W, A. Weed Control. Advance In Acvon. l:200-32CU9Uo) 5. Csvldeon, W. B,, et al, NltrRte polsonlnr of livestock. Con, Jour, of Comp. Med. Vol, 5, 1^41, 6. Srlckeon. I. C., Seely, C. T., and "lapes, K. H, Effect o f 2,U-o upon the protein content of wheats. Jour, Amer, Boo. Arron. o:6c,a*66o(iciig) 7. dlbert, C, S-reon, H. F,, Bradley, W, 8. A Beath, 0 , A. Mitrte aocuKulrttnn In cultivated nlanta and weeds. Wyn, Kerr, Evp, Statton. Bull. 277, 19^6. F. Ortpsby, 8, H, A Farwsll,<K, D, Some affeots of herbloldee on paeture end on frraMntr livestock. Mich, Affr, Ex, Station puart, Bull, Yol. 32, No. 3, Feb. 1^50. 0 , Helpecon, . A. The effect of P,U-D on wheat, Proc. ^th Ar.n. Mooting North Central Weed Control Conference, Deo. loii7 (Topeka, Kansas) pp, 77*^, 10, Hulllncrer, C. H, Cfreota of 2 , - 0 on the nl t^o.-ran and carbohydr^.t e Dotabollaa of the corn pls*'.^, Hec, Per, N.C.'.-vC.O., Sprl noTl eld, 111, 1 BU, Seo. VITI, AVutr.-ct 5. 1 1 Kephart, L. W, kcdarntor of discussion at l't, iul ue^tlnc* of N.C.W.C.C, Proc, 2nd Ann. Mastn? N.C.Vw.C.C., fit. Paul, Minn. 1<*5, p p . ^*75* 12, Kltohall, J. V., et al. Tolerance of farm animals to feed oontalnln? 2,4-D add. Jour, Anlu-., Bel. l,:yj-2'}2 (1Q,*6j 13* Olson, 0, E, i Whitehead, content of anra* Bourh Dakota plante, -roo. S. D, kca \, of -Joi; 20: o,;-.l01 (10^0 ) ~ 16134 7 14. hws U-Przj, Cj L Uillard, C, J, Effeot of 2,4-D on orotoln c:^w..: cf nosesrch Report N.C.W.C.C. Reaearoh Comralttee p, 77* 15 Tc.nncVj, Ja Ca Tfccto of 2,4-D on su^rar beata. Cryatal-ized fV-uo Llrt'XC c - ' ; beata. Vol. IV, No* 1, Jan# 1950* Otbcr- cite- by nano only ara from URDUbltahed eommunlcattona O ji-0 v-i'iti.0 DOW 7 5 5 4 4 0 16135 ism f DOW 755385 c*o-c acsbfes ccwenevca B fiA|NS fC,HV S A L C 3 COIFTFYl C C S IN iA.SCtbCO FLrOt SL AACNf vLUF HCISA ASr-t iNGTCN .A NT LOUid CwtS'CLANO CH .O. lUCSaTCOON feLATTLS CITfOlT BOSTON Tee @rj Chemical Company MIDLAND * MICHIGAN December 9 , 1949 ntliard L i Stilt, n g O l S u l t U T ` o .1 O b ' nical Salea o oCoM fA r^. O Subject: Toxicity of 2,4-D and 2,4,5-T (l) On pace 8 of your paper entitled "The UBe of 2,4-D, 2,4,5-T and Other herbicides for Vegetation Control on Transmission Rlghts-of-Way" there appears under V item 3, a section entitled "NonpoiBonous". ke have iccisod this section of the paper over and would suggest that this section be replaced by the following including the seven references given: * "3-Toxlcity 2,4-D and 2,4,5-? are both low in toxicity to men and animals an>_ A're easy to handle and use with safety. "fiitchell and co-workers (l) report that cattle and sheep were pastured on areas freshly sprayed with 2,4-D without ill effects; that a cok. was giver* daily doses of 5.5 grama of 2,4-D for 106 days without ill effect or contamination of milk; and that a man took 0.5 gram of 2,4-D dally after a meal for 21 days without ill effects. "njorn and Northen (2) report uhoir work with chicks and in ccn- ciuslor. state: The .question might be raised as to the possibility of enir.;.. oc'lr.(c killed by feeding on planto which had been sprayed with 2,4-D. At a cp-aylug rate of 1 lb. of 2,4-D/acre, a chicken weighing 1 kg. would have c cc-rsat.e a 11 cf the 2,4-D applied on 71 ft. within a day or two to obte a leiii&l dose. * "The results of studios on several species of laboratory animals .'{.ported by Hill and Carlisle (3) and oy iiuchur (4) indicate that 2,*.-> -r ! .. In tosJelly when taker* by mouth for all the species studied. The effect of 2,4-D on fish has been reported by HarriBecn an.* M (r) Lynch et ai, in a report of the U.L. Dept, of Interior, Flan So-vi co (February, 194?) , concluu r that 2,4-D presents no pc.,, a : eentrat ion usually neecleu for tn control of aquatic *.*..... 1613 k^r----- I :lia'.-J in.ilth P2 DeceniDer 9, ly4y "Eide (6) studied the effects of various insecticides on honeybees .nd concluded that 2,4-D was "non-toxic" under practical conditions of use. "The toxicological information available on 2,4-D is much more ex tensive than that on 2,4,5-T, probably because it is the older of the two products. All the toxicological information available (7)# however, indicates that 2,4,5-T is essentially the same as 2,4-D in toxicity to warm blooded animals. REFERENCES DOW 1 7 5 5 3 8 G "(1) J. W. Mitchell, R. E. Hodgson, and C. F. daetjens (U.S. Dept, of Agrl., Washington D. C.) Tolerance of Farm Animals to Feed Containing 2,4-Dichlorophenoxy Acetic.AcId J. Animal Scl 226-32 (1946) (2) Kolvln K. Bjorn and Henry T. Northen Effects of 2,4-Dichlorophenoxyacetic Acid on Chicks Science, Nov. 5 1948 Vol 108, pg. 479 (3 ) Edwin C. Hill and Harold Carlisle (Camp Dletrlck, Frederick, Md.) Toxicity of 2,4-Dichlorophenoxyacetic Acid for Experimental Animals gi J. Ind. Hyg. and Toxicol. 29, 83-93 (1947) (4) Nancy L. R. Bucher (Harvard Univ.) Effects of 2,4-Dichlorophenoxyacetic Acid on Experimental Animals. Proc. Soc. Expt'l. Biol, and Med. 6, 204-5 (1946) (5) J o b . W. E. Harrlsson and Edward W. Rees. 2,4-D Toxicity I-Toxicity Toward Certain Speciea of Fish Am. J. Pharm. 118, 422-5 (1946) (6 ) Paul M. Eide Insecticides on Honeybees J. Econ. Entomol. 40i, 49-54 (1947) (7 ) Unpublished Data Biochemical Research Department The Dow Chemical Company" (2 ) If you have any questions regarding this suggested sub stitution we would be glad to discuss them with you. Sincerely yours, VKR/mg ccs L. W. Scuthwick V. K. Rowe Biochemical Research Department