Document B5Kq5eYGxZ83ZQnLYjrBq29R4

* a/. A* MANUFACTURING CHEMISTS ASSOCIATION 1825 CONNECTICUT AVENUE, N.W. WASHINGTON, D, C. 20009 (202) 483-6126 October 21, 1975 To: Subj : Technical Panel on Vinyl chloride Research Action, Information, and Reference Items ACTION: 1. Please note that confirming arrangements with Chairman Torkelson, the next Panel Meeting has been rescheduled for December 11 and the Research Coordinator's meeting for Decem ber 10 at MCA headquarters. Tentative agenda to follow. The Project Manager will be unavailable on dates previously chosen, December 8 and 9. i 2. Industrial Biotest Laboratories (IBT) has requested permission to present the final Vinyl Chloride report at the annual meeting of the American Industrial Hygiene Association in May 1976. Please review the enclosed abstract on "Inhala tion Studies with Vinyl Chloride" and be prepared to vote on it at the next meeting. In the interim, comments may be sent to me with copy to Dr. Torkelson. IBT has already been informed of Dr. Torkelson's suggestion to add the phrase "...consistent with dose" to the last sen tence and his questions about whether the animals are all ex pected to be dead and pathology completed by the deadline. IBT was also reminded that the full paper should be reviewed by the Panel before presentation. INFORMATION: 3. A revised (October 1) Financial Statement is enclosed, correcting errors in the one distributed with the minutes of the last meeting. Also, subtotals have been added. The key change is in Grand Total Balance on Hand to $305,935. SL 068582 OCT 31 1975 2 4. A possible circulatory problem relating to Vinyl Chloride is brought up in Dr. Mayo Smith's enclosed letters of October 13 and 14. Answers to the questions posed should be suitable discussion items at the next meeting. 5. Updates on points raised in Dr. Torkelson's letter of September 22, enclosed, are in the following four items. 6. The subject of greatest interest, pathological backup for the National Institute for Occupational Safety and Health's (NIOSH) listing of angiosarcoma cases is still under investi gation. The Project Manager received a copy of EPI-74-63-2, Angiosarcoma of the Liver Among Vinyl Chloride Workers, Louisville, Kentucky, May 13, 1974 from Dr. Henry Falk of the Center for Disease Control. Enclosed is a memorandum from Dr. Marcus Key with attachment which appears to cover case numbers 14, wire coating operator and case 15, accountant in NIOSH's Table 1 on VC/PVC workers of June 25, 1974. Further follow-up correspondence and telecons have not yet yielded all of the information desired. 7. A letter of October 3 from Dr. James Woods of National Institute for Environmental Health Sciences (NIEHS) is also enclosed. However, the December 31, 1974 proposal from Midwest Research Institute and modification of May 16, 1975 are too long to include herewith. A listing of NIEHS extramural projects on Vinyl Chloride and cover letter of October 15, 1975 from Dr. Braun are enclosed. 8. The Consumer Product Safety Commission (CPSC) program is outlined in the Project Manager's communication to the Panel May 8, 1975 and in the enclosed letter of May 6, 1975 from Dr. R. M. Hehir to Dr. Torkelson. In a telecon October 1, 1975 CPSC's Dr. McLoughlin informed the Project Manager this study is going into it's seventh month and no patterns (e.g. in mortality) have yet emerged, nor have reports been written on it. The first sacrifice is scheduled for November 4, 1975. 9. In a telecon September 26 with Dr. Stara of EPA, the Project Manager learned the "Transplacental Carcinogenesis" work is to be done at Kettering Laboratory under the direction of Dr. Bingham. Chambers are being modified and it may be SL 068583 4 -3- months before start up. No new information has been received on EPA's "Automobile Interior" project. REFERENCES: 10. The September 1975 issue of Chemical Engineering Progress, contents page enclosed, includes four papers on Vinyl Chloride Emission Control. Lead authors of two of these papers, Dr. Bell and Mr. Wheeler, are also members of our panel. 11. First page of article on Vinyl Chloride Exposure in a Controlled Industrial Environment from the July '75 issue of Archives of Environmental Health. 12. A booklet on Health and Safety Guide for Plastic Fabricators prepared by NIOSH is available from the Office of Technical Publications, National Institute for Occupational Safety and Health, Post Office Building, Cincinnati, Ohio 45202. 13. A 2nd edition, July 1975, of The Determination of Vinyl Chloride, A Plant Manual is available from Chemical Industries Association Ltd., Alembic House, 93 Albert Embankment, London, SE1 7TU. 14. Enclosed is the first page of an article on "Comparison Between In Vitro Toxicity of Polymer and Mineral Dusts and Their Fibrogenicity" from Annuals of Occupational Hygiene, Vol. 16. 15. The following reports and articles are brought to ycur attention: Measurements of Vinyl Chloride From Aerosol Sprays by Bruce W. Gay, Jr. et al.; EPA-650/4-75-020, May 1975 Environmental Monitoring Series report on Ambient Air Measurements of Vinyl Chloride in the Niagara Falls Area; Atmospheric Oxidation of Chlorinated Ethylenes report by B. W. Gay, et al., of EPA's Environmental Science Research Laboratory at Research Triangle Park, North Carolina 27711. M?/mj Enclosures SL 068584 Inhalation Studies with Vinyl Chloride M. L. Keplinger, J. W. Goode, D. E. Gordon, and J. C. Calandra Industrial BIO-TEST Laboratories, Inc. Northbrook, Illinois 60062 A study was conducted to determine the effects from inhalation of vinyl chloride monomer to rats, mice and hamsters. The study was designed as a life-span study in these species which is usually 1-1/2 to 2 years. In this study, 200 rats, hamsters and mice (100 of each sex or 600 animals total per exposure group) were exposed to 50, 200 or 2,500 ppm vinyl chloride vapor 7 hours per day 5 days per week. Mice were exposed for 9 months while rats and hamsters were exposed for 12 months. The animals were then held for the rest of their natural lives. The rats were COBS Charles River; mice were CDI Swiss Charles River; and the hamsters were Golden Syrian from the same source. Food was re moved during exposure, water was present and no bedding was used at any time. All 600 animals per level were exposed in a single chamber. The chambers were operated under dynamic conditions, sealed and under slight negative pressure. This was done so that in the case of an accidental leak, room air would flow info the chamber instead of contaminated air flowing out of the chamber. The concentrations in the chamber were analyzed using gas-liquid chromatography- An automatic sampling device allowed samples to be drawn from 3 locations in each chamber. The concentrations at all loca tions in each chamber were monitored every day. Moribund and dead animals received gross autopsies and gross lesions were photographed. The major organs of all animals were fixed, prepared and examined histologically. Findings included angiosarcomas in the liver, alveologenic adenomas in the lung and adeno-squamous carcinomas in mammary glands. SL 068586 ALLENTOWN. PENNSYL VANIA 18105 13 October Vj7S OGT 1 41975 Or. T. Z. Torkelson Dow epical Conoany Mealth Sfnvlr. ''esearc'. W" 0 Mldlrn Mdland, Michigan J8MS Dear T?'4: You will recall that when Or. Tamburro iade his presentation to the Research CooHirators at the C*. on 8 Sentember 197S under his Medical Surveillance Program te listed the following: "1. "Inchenilcal 2. T Ml 01*0/ 3. Pulmonary d. erdlec 5. M1storv and pnys1cal It is "v opinion that rcost comanlrs are not roakinn a cardiac examina tion under their current nodical surveil'ancc jf those people exposed to vinyl cnloridc. I think It pertinent teat vou cr perhaps better Milton Frrifeld eol; each the n-'.sr CT-ranirs In the MCA program Sincerely yours. '.nS:C ty/ cc: ^Milton Frelfeld. S^* ALLENTOWN, PENNSYLVANIA 1B10S 1*1 Jctober T 975 This is tur.s'*r -,o :.iy ;iut^ to you 4110 Mile rreifein ur 13 f)ctober. Attached is -in arth.ie ml King 6rd, t.,e only ;*vc producer in Sweden an! on; of -^cil'ienc?. You will recall -hat !lc`; Wheeler at our September meetlnq mentioned the 'iftC shewed a.ionc 'ahricators according to my notes diseases of circulatory system to b;* higher thin oxDecteJ is 1 ,576 observed with expected 1,444. You nay also rp.ier.ijcr that taury .Johnson thought these differences ;jrr: significant. The Ker-a'-.'orJ rer.nr: ler-*5 further evidence that we should inraellately contact all member comoanies of the 'CA Vinyl Cnlcrlde Program. My question of yesterday was . tht.r anv cardiac y\.v:ina:``or's are made and r.y question of today Is *hat have been the findings, If so done. With test regards. Sincerely yours. 06858s V IN VI, C'llIf Jilt IDE RESEARCH PROGRAM Financial St atrmont - August 2H, 1975 Revised as of October 1, 1975 Invoiced (Committed) Epidemiology Study Tabershaw/Cooper Assoc. <al Health Study of VC Workers (6/13/73) lb) Adjustment/- Travel (8 iG/73) fc) Ad]ustment/Extension (3/12/74) (d) Retabulation of Data (7/13/74) (e) Study of Workers/ 4 plants (11/5/74) (f > Extended Epidemio1ogy S t udy (4.22/75 Sub--Total $ 91,940 $ 53.597 $144,537 2 . Chronic Inhalation Studies Industria1 BIO-TEST $190,281 Labs fa) Origina1-Protocc t (2/1/73} (b) Additional Animals- IOC rats (5/22/73) (Restart-Agreement (0.31/73) (c} i b-T L Contract Adjustments $ 50.000 Sub-Total $240,201 Received $ 91,940 $ 51,`jn $143,853 $ 190,281 $ 49,405 $239,686 Research Contract Time fJ l shnr sonu s.nts_________________ Administrative Research Trave1 Wise. Contracts Total id Balance On Contract Ha)nneo on Eland $ 71,345 $ 3,950 $ 5,250 $ 1,000 $ 10.350 $ 12,000 $123,895 646 $ 646 -0-0- $ 45 $ 91,895 -0$ 45 5 18.625 $110,520 $2,665/1 $279/2 $149,000 $130,375 $ 15,000 $164,000 $1,490 $1,490 $2,665 $279 $ 10,000 $140,375 $ 91,940 -0- -0- $ 19,271 $111,211 S.Pi 3T5_ $13,375 $ 32.642 $ 32,642 $143,319 $ 46,962 $18,625/3 $ 1.498 $144,817 $ 5,000/3 $23,625 f 47,907 $ 94,869 3. Dow Studies (a) Metabolic (b) Teratology (c) Extension of St udfos Sub-Tota1 $101,250 $l49,990 $251,240 $101,250 $148,205 $249,455 GRAND TOTAL $636,058 $632,994 Note-* 1. Gasque, Kociba & TorkeJson to Italy 2. Cylinders for Vinyl Chloride 3. Due I B-T L - Receipt of Final Report $ 50,000 $ 20,000 $ 70,000 $357,895 $ i,im $1,031 0-0- -0-0- $ 50,000 $ 20,000 S 70,000 $3,175 $2,665 $324 $320,895 St 068589 $ 70,000 1.031 $ 71,031 $ 31,250 -0-0- $147,174 $178,424 $327,059 $37,000 $305,935 SEP 2 4 B7S THE DOW CHEMICAL COMPANY September 22, 1975 BENNETT BUILDING 2030 DOW CENTER MIDLAND. MICHIGAN 40640 Mr. Milton Freifeld Manufacturing Chemists* Association 1825 Connecticut Avenue, NW Washington, D.C. 20009 One of the companies sponsoring the studies on vinyl chloride re ceived the following information in response to an inquiry "on the various studies of vinyl chloride (VCM) being conducted as recommended by the Vinyl Chloride Task Force." The Office of Toxic Substances has completed the preliminary in vestigation for EPA's epidemiology study, which will be started soon. In EPA, the Office of Research and Development's Health Research Laboratory in Cincinnati, Ohio, 45268, is sponsoring a study: "Toxi cological Investigation of Vinyl Chloride with Relevance to Non-Worker Populations, with Emphasis on Transplacental Carcinogenesis and Co factors" (Contract #68-03-2148, Project Officer, Dr. Jerry Stara). No data have yet been derived. Another study, "Sampling of Auto mobile Interiors for Vinyl Chloride" (Contract #68-02-1404, Task 1, Project Officer, Dave Benny), is now underway, being sponsored by the Control Systems Laboratory, 0RD, EPA, Research Triangle Park, N.C., 27711. Several studies are being sponsored by other agencies. You should contact them for specifics: Consumer Product Safety Commission, 7315 Wisconsin Avenue, Washington, DC, 20014 (Contract #72-2084, Project Officer, Dr. Robert Hehir). National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27711 (Contract #210-75-0051, Project Officer, Dr. James J. Woods). The Center for Disease Control, Atlanta, Georgia, 30333, is an alyzing 300 reported cases of hepatic angiosarcoma, to determine all pbssible correlations. Dr. Henry Falk is managing this study. Please attach a copy of this letter with your next mailing to the sponsoring companies. Sincerely, Theodore R. Torkelson Corporate Medical Department SL 068590 * 1 MEMORANDUM Mr. Edward Klein Office of the Solicitor Department of Labor /6y DEPARTMENT OF HEALTH, EDUCATION, AND WELTARE PUBLIC HEALTH SERVICE CENTER FOR DISEASE CONTROL NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH DATE: August 22, 1974 FROM : Directbt SUBJECT: OSHA Public. Hearing on Vinyl Chloride Enclosed is a review of the Connecticut cases by Dr. Louis B. Thomas, Chief, Laboratory of Pathology, National Cancer Institute, which should be included in the record of the OSHA Public Hearing on Vinyl j Chloride. ' In accordance withPublic Health Service policy, I haveblacked out the names ofthepatients. However, for yourpurpose it should be sufficient to note that case #5 in Dr. Thomas' memorandum was the accountant at the vinyl cloth plant, and case #6 worked in an electric company applying PVC insulation. j .. I Enclosure Marcus M. Key, M.D. /J Assistant Surgeon Ge^^ral > . ,,c.-. 068591 SL It! MUNT '-1' I II.ALTW. I OU^AHON Af.'N V/ELPAK'I' II. 1 ->I i tii't.tc. iicai. m .iMvtr.L ija 1in. ..'L i.v.m i it i .or hlm t >i ntiiir.UA. h.'.'iii i'ntt 31 July J97A naiicisal camcch uistitute Dr. Philip I.nndrigan Communicable Disease CcnLer 1f>00 Clifton Knud, N.E. Atlanta, Georgia 30322 Dear Dr. Landrjgan: On July X9th wo sent you pathology reports for six of the eight TiMt.> ! ic ut r . l.ucX'c .1 are reports for the otiier two patients; After comnlctire the individual reports. Dr. Popper, Dr. Lingenan find I reviewed the eight cases once more in order to make some evaluation about their possible similarity or dissimilarity to lesions seen in VC-rVC workers. Our comments about this are listed below: CD 4HK2S9^'-t- believe the angiosarcoma of the liver of this ]gLiont is different from most of the angiosarcomas seen in VC-PVC workers. Sinusoidal dilatation and/or megalocytosis of hcpatocytes were not seen. Also there was no hepatic fibrosis similar to that seen in the VC-PVC workers. (2) fti&BZS3S9fc' Carcinoma involving pancreas and liver, possibly primary in the pancreas. We do not have a carcinoma of this type among the known VC-PVC workers whose lesions we have reviewed. (3) carcinoid type bronchial adenoma seen in the lung v tni:; paLuc.t almost surely has no relationship to the hepatic lesions (,? he:vingiomns) in the liver. We have not seen any bronchial adenomas in the VC-PVC worker sections we haw examined. (A) angiosarcoma in this patient forms capillary, slit-iii spices and replaces hepatic tissues. Wc only occasionally found this type of histological pattern in thd angiosarcomas of the VC-PVC workers and, in those patients, always also found :..ul Liccnt r i c areas of angiosarcoma with a sinusoidal and/or papillary pattern. We did not see Lhcse types of pattern in 'Jr. Mullov't; section. Thus wo do not think his hepatic ang i os.ireoma is characteristic of the angios.il comas seen in the VC-PVC worker:;. Also 068592 SL Page 2 - Dr. r)I; 1 Jp I.andrijym liver is defi n i to Jy cirrho tic with Those f enturo ; al so were n ot r.oen with hif-p.it.ic f ibr os if; and with or ' * cannot be eertain TTi i:. c ]; :Loi og i c feature an;; ion.arc urns somewhat "1i.brobl angina ^ r coii*< j n in most of tbc severe 1 other 1 1 i. V.' tologicn1 feature VC-PVC worker :* iic pa tie lea ions; na: tect or ial and err/ e lop in:; f eacures > colls. portal Cra c.L fibre.; is, and ' hopato ayt os. In summary, there ar simile rifles Llir.t we cannot exelud "Vv"e-i',"* d type case II i.c-. the colls of the .tic," is dissimilar to >PVC workers. However as a so-called (6) ease refer to the note on our surgical path^ ovy r.., .,r-j S74-15C6. In brief. ue are not completely certain that this is an angiosarcoma of the liver or even a primary .sarcoma of the liver. It is not like any of the other tumors we've seen in the. livers of VC-FVC workers. (7) -The histological features of the hepatic ani"'jf reo. 1 i iJ 11 <1* portal Lract fibrosis seen in this case are saw.iia in nearly all respects to the lesions we have seen in tcos of the VC -I'Ve workers' livers. (8) have reviewed needle biopsies only from this p^ljosl's angiosarcoma. The amount of material is insufficient for a definite comparative statement, but we do not see the histologic features which we believe are most characteristic of the angiosarcomas in VC-PVC workers. In conclusion vc interpret five of these crar having definite hepatic angiosarcomas and an additional case iQMBBSSSSSSSIf^ as possibly having a hepatic angiosarcoma. In one pa tier... the overall histciagic lea lures are the same as at vary sim'iar io the hepatic lc:h scon in most of the VC-PVC. workers. In another case 435E9BB22B^ffil9 there 3rc several similar features and one or two dissimilar ior turns. We wjint to emphnsiao that we do not think there is any single, histological feature either of the angiosarcomas or of the hepatic: fibrosis which is pathognomonic of vinyl chloride exposure- Per example, nil the changes we've seen in the liver;; of the VC-PVC workers can apparently he produced by exposure to arson teals. However, certain types of hepatic fibrosis, SL 068593 Page 3 - Dr. Philip Landrjgan sinusoidal dilatation, mu]ticentric angiosarcomas with sinusoidal, papillary and cavernous patterns together with mcgnlocytosis of hcpatocytcs collectively Torn a spectrum of hepatic lesions which are "characteristic" of the VC-PVC workers' lesions. It is with those facts in mind that we have attempted to evaluate the Connecticut cases and compare their similarities and dissimilarities with the VC-PVC workers. Thank you for getting this material for our review. We would like to keep the submitted sections awhile longer in order to Lake photo micrographs of the various lesions. Also our conclusions about some of these car. .s might be more definite if v:e examined additional crc t i-Ciu ci* rj.p.1 rw-d nddi .icn -1. Grid spccisl 5*t5v*c* Ua will write ycu later about individual coses which might be studied further. Sincerely, Louis E. Thomas, M.D. Chief, Laboratory of Pathology TABI.K 1 l CONFIRMED CASES OF LIVER ANGIOSARCOMA. AMONG "'WORKERS EXPOSED TO VINYL CHLORIDE OR POLYVINYL CHLORIDE COUNTRY Sweden CASE . #. * * */ BIRTH DATE 02 11-27-11 Uni ted States 01 Ln;t ed States 02 United States 03 United States 04 United States 05 United States 06 United S t a tes 07 United States 08 United SLntcs 09 Uni ted States 10 I'ni ted States a Uni ted States 12 United States 13 W. Germany 01 W. Germany 02 Great Britain 01 Norway 01 Sweden 01 . 00-00-22 00-00-34 00-00-15 00-00-24 00-00-12 00-00-29 05-03-22 05-06-20 00-00-31 00-16-! 3 05-27-09 11-17-18 12-01-21 07-26-31 06-04-30 00-00-01 12-23-15 06-23-27 United States 14 United States 15 00-00-13 00-00-25 1st VC or PVC EXPOSURE^ DX ANGIOSARCOMA AGE AT DX VC MONOMER PRODUCTION WORKERS YRS 1st EXP TO DX 00-00-45 05-15-72 61 27 POLYMERIZATION WORKERS 12-09-48 11-15-55 11-28-45 07-06-52 06-19-44 01-17-62 08-00-44 10-07-46 05-28-45 06-00-51 10-14-46 09-13-49 08-19-44 10-14-57 10-01-57 00-00-46 03-00-50 03-00-71 49 ` 22 05-00-70 36 14 12-00-73 58 . 28 08-00-67 . 43 ' 15 04-00-64 52 20 02-00-74 45 12 00-00-68 45 24 08-00-61 41 15 03-01-74 43 29 05-00-68 55 17 03-00-70 61 23 05-00-69 . 50 20 05-00-74 53 30 00-00-71 40 14 00-00-69 39 11 12-00-72 71 26 12-20-71 56 22 mwsmxxMMmmRXxxBo SECONDARY MANUFACTURING 08-18-38 06-00-73 60 36 00-00-00 07-00-72 47 00 TOT YRS EXP 23 16 13 28 15 18 12 18 15 17 17 23 15 30 14 11 20 21 00 00 Note: *00' indicates unknown date 06^5 I June 25 DATE OF DEATH 08-16-72 03-03-73 09-28-71 12-19-73 01-07-68 04-Q9-64 Alive 03-23-68 08-29-61 ALIVE 05-10-63 03-16-70 05-02-69 ALIVE 12-14-71 01-25-69 12-00-72 01-04-72 l07-03-73 oj 02-15-73 U. * * OCT 81975 department of health, education, and welfare PUBLIC HEALTH SERVICE NATIONAL INSTITUTES OF HEALTH October 3, 1975 NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES P.O. BOX 12233 RESEARCH TRIANGLE PARK. N.C. 27709 Mr. Milton Freifeld Project Manager Vinylidine Chloride Research Manufacturing Chemists Association 1825 Connecticut Avenue, N.W. Washington, D.C. 20009 Dear Mr. Freifeld: In keeping with our agreement to send you information regarding our research activities on vinyl chloride and related substances, I am enclosing for your information a copy of our contact proposal entitled "Evaluation of the Environmental Toxicant, Vinyl Chloride Monomer (VCM). Included is an addendum describing additional studies we are conducting on vinylidine chloride, as well as some extra VCM tests which were added after the proposal was written. The work on this contract has begun this September, and we will be happy to send you copies of the progress reports as they become available. Please continue to send us whatever information you derive from your studies in this area. Yours truly. Enclosures -Barnes S. Woods, Ph.D. Head, Biochemical Toxicology Section Environmental Toxicology Branch SL 068596 LEPuiT* .\" Ur HEALTH. EDUCATION, AND WELFARE MJBUC. HEALTH SERVICE . AIIC ,AL INSTITUTES OF HEALTH f.'.TIONAL institute of envirdmmental HEALTH 3CIENCFS P.o. BOX I2.'3J RESEARCH TRIANGLE PARK NC Z7.-JU October 15, 1975 Dr. Milton Freifeld Assistant Technical Director Occupational Health Manufacturing Chemists Association 1825 Connecticut Avenue, N.W. Washington, D.C. 20009 Dear Dr. Freifeld: This letter is in response to your inquiry of October 2, 1975. Information on vinyl chloride is enclosed, and information only on extramural projects dealing with vinylidene chloride and polyvinyl chloride is enclosed. Inquiry to NIEHS staff about the other compounds is in process; the resultant information will be forwarded to you when received by this office. Sincerely, Enclosures 068597 October 8, 1975 A VINYL CHLORIDE RESEARCH NIEHS OCT 2 0 1975 Intramural In cooperation with Dr. Robert T. Drew and Mr. Mike Riley, a mutagenesis prescreen using Salmonella typhimurium with vinyl chloride is being conducted to test a system for handling gases in tier-one testing. Contract Ongoing vinyl chloride (VCM) studies (MRI Contract No. NIH-NIEHS-722084) seek to determine the biochemical and pathological alterations in specific organ functions of rats and mice chronically exposed to low and mid-level doses of VCM or vinylidene chloride (VDM). Dr. James Woods is the project officer for this contract and should be contacted directly if more information is needed. tAtrainui a LIST OF PROJECTS 1. 5 R01 ES 01027-02 SOBELS, Frederick H. -Department of Rad., Gen., Chem. Mutagenesis University of Leiden Leiden, Netherlands Induction of Genetic Damage by Chemical Mutagens. Studies include preliminary screening, with Drosophila as the test system, of a number of suspected mutagens, including vinyl chloride, to be followed with investigation of effects on male germ cell stages and determination of mutagenic mechanisms. 2. 1 R01 ES 01150-01 . VAN DUUREN, Benjamin L. New York University Medical Center New York, New York Carcinogenic Intermediates and Metabolism of Vinyl Chloride and : -Analogs. Study based on the premise that an epoxide not vinyl chloride per se is the proximate carcinogen. Will attempt to determine the transfor mation and action mechanisms of vinyl chloride and/or its metabolites in liver. 3. 1 R01 ES 01287-01 (Energy Award) SICILIAN), Michael J. University of Texas System Cancer Center Houston, Texas Multiple Loci Screen for Mutations in Mammalian Cells. Study of the detection of mutations in cultured mammalian cells (mainly Chinese hamster ovary cells) by simultaneously screening cloned isolates for electrophoretic variants at 50 or more loci, using a number of known or suspected mutagenic agents, including vinyl chloride. 4 068^99 St- . > Extramural Page 2 - LIST OF PROJECTS 4. 5 P10 ES 00002-13 WHITTENBERGER, James l. Harvard University School of Public Health Boston, Massachusetts Occupational and Environmental Health. Studies in the Environmental Toxicology Group include the determination of binding sites in relation to toxicity and mode of action of vinyl and vinylidene chlorides. Dr. Richard Monson, Department of Epidemiology, and others are engaged in mortality studies involving identification of cases in different locations for diseases (cancer, leukemia or congenital anomalies) caused by various factors, including vinyl and vinylidene chlorides. 5. 5 P10 ES 00159-10 SUSKIND, Raymond R. University of Cincinnati Cincinnati, Ohio Center for the Study of the Human Environment Methods are being developed for analysis of low ambient levels of vinyl chloride and for evaluating permeation tubes for preparing accurate gaseous vinyl chloride standards. 6. 5 P10 ES 00928-02 SELIK0FF, Irving J. Mount Sinai School of Medicine City University of New York New York, New York Center for the Study of Biological Effects of Environmental Agents. Thjs laboratory has a number of studies underway dealing with medical surveillance of workers exposed to asbestos and vinyl chloride in the manufacture of vinyl floor tiles, mortality experience of a cohort of vinyl chloride-polyvinyl chloride workers, prevalence of vinyl chlorideassociated disease among exposed workers, and chromosome damage induced in exposed workers by vinyl and polyvinyl chlorides. 4 4 i 4 U.S. CONSUMER PRODUCT SAFETY COMMISSION WASHINGTON. D.C. S0S07 May 6, 1975 Dr. Theodore R. Torkelson Corporate Medical Department The Dow Chemical Company Bennett Building 2030 Dow Center Midland, Michigan 48640 Dear Dr. Torkelson: Thank you for your letter dated April 23, 1975, regarding CPSC's proposed protocol for inhalation studies on vinyl chloride. As I remember, you have a copy of the original protocol scheduled to be performed at Edgewood Arsenal. Attached is a copy of the proposed changes. In regard to the schedule, the.acute study of 1 hour only with rats and mice and holding for 24 months is now in its second month. The three generation reproductive studies are now in the 60 day exposure stage. The sub-acute inhalation stage is entirely new and is just beginning. If I can be of any further help, do not hesitate to call or write. Attachment Robert M. Rehir, Ph.D. Director Bureau of Biomedical Science st. 068601 CONSUMER PRODUCT SAFETY COMMISSION During a visit to Biomedical Laboratory by Drs. McLaughlin and Uyer on 27 March 1975, it was mutually agreed by the contract project officer, Dr. McLaughlin and Dr. McNamara, Edgewood Arsenal Contract Administrator, that the following technical changes would be made in the toxicological testing of Vinyl Chloride monomer: 1. No biochemical or enzymatic work would be performed in the vinyl chloride studies. 2. The three generation reproductive studies will be changed as follows: a. The number cf animals per dose will be increased from 10 to 25. b. The exposure concentration and time of exposure will be 50 and 500 ppm, 5 days week/10 weeks. c. The parent generation will be held and observed for 2 years. d. No teratology studies will be performed. 3. A sub-acute inhalation study will be added to the acute work. The exposure schedule is as follows: Sub-Acute Vinyl Chloride Inhalation Study (Exposure Schedule) Dose Species Number Frequency Level_____________(Strain)________________ Exposed_____________of Exposure 50 Rat (Fisher) Mouse (A/J) 180 180 5 dy/wk - 20 wks It ft 500 Control Rat (Fisher) Mouse (A/J) Rat 50 ppm 500 ppm 180 5 dy/wk - 2 wks 180 It ir 100 _ 100 " - Mouse 50 ppm 500 ppm 100 100 -- SL 068602 The observation and sacrifice schedule is as follows: Dose level (ppa) Sub-Acute Vinyl Chloride Inhalation Study (Observation and Sacrifice Schedule) Time of Observation & Sacrifice (Months) 8 Rat Mouse 50 20 20 500 20 20 Controls 50 ppm level 10 10 500 ppm level 10 10 Totals 120 20 20 20 20 10 10 10 10 120 16 Rat Mouse 20 20 20 20 20 20 20 20 10 10 10 10 10 10 10 10 120 120 24 Rat Mouse 50 50 50 50 50 50 50 50 30 30 30 30 30 30 30 30 320 320 Total Animals: Rats - 560 Mice - 560 SL 068603