Document 0qOY2Kq2eG06KkQEMz1DMgyNR

ISNOUTTHHCEEHRANURNLDIETISESTDTORNSI,CTATWTEEOSSFT DVWIISRETGSRTINICVIATIRGCOINURIAT DJoAfeMcEtehSaesMeEd. ,sAtaeDttKeIaNolS,f, AR adlmphinEis. trAa tdokrins, ))) P l a i n t i f f s , )) vs. MCOoNrSpAoNrTaOtioCOnM, PANY, a D elaw are ) )))) No. 81-2098 D efend an t. )) APPEARANCES: M ePsesyrbtsoy. nWC, .a lw ell, S tu a r McCormick t Calw ell, & Jr., Esq. For P lain tiffs, M eLsosvrbsey., Bowles, McDavid, G raff & aCPn.hdaMr liecsh aMe.l Love I I I , Esq. Pleska, Esq. For Defendant, Thomas M. B is tlin e , E sq. MC oounnsasnetlo. Company IT IS STIPULATED AND AGREED by and betw een counsel fo r the p la in tiffs and counsel fo r the defendd an t th a t th e d e p o sitio n o f CLAYTCN F . CALLIS may be taken pursuant to Rule 26(a) of the F ederal Rules of C iv il P rocedure, on b e h a lf of the p l a i n t i f f s , on J u ly 1, 1983, a t th e R adisson H o te l, Room 215, 9 th & J A M E S MAY R E P O R T IN G SE RV IC E t ! 1 C onvention P la z a , S t. L o u is, M isso u ri, b e fo re M. JOY 2 SPRINGER,a N otary P u b lic w ith in and fo r the County 3 of Madison, S tate of I llin o is ; th a t the issuance of 4 n otice and dedimus is w aived, and th a t th is deposition 5 may be taken w ith th e same fo rce and e f f e c t as i f a l l 6 Federal ru les and statu to ry .requ irem en ts had been 7 complied w ith. 8 IT IS FURTHER STIPULATED AND AGREED th a t any 9 and a ll objections to a ll or any p art of th is depo 10 s itio n ex c ep t o b je c tio n s as to form o f the q u e stio n s 11 asked or answ ers g iv e n , a re hereby re se rv e d and nay. be 12 ra is e d on th e t r i a l o f th is c a u se ; and th a t th e s ig n a 13 tu re o f th e deponent is n o t w aived. U ** * *' * * * * * * * 15 l 17 18 19 CLAYTON F . CALLIS 20 produced, sworn and examined on b e h a lf of the p l a i n t i f f s , 21 deposes and says as fo llo w s : 22 EXAMINATION 23 BY MR. CALtfELL: 24 (Whereupon the r e p o r te r marked P la in - , 25 t i f f s ' D ep o sitio n E x h ib it #170 (M onsanto JAM ES MAY REPORTING SERVICE #236180 and #2.36181) c o n sistin g of 2 pages; i.V E x h ib it #171 (M onsanto #8322233, #3322244 2 3 and #8322245) consisting of 3 pages; Ex 4 h ib it #172 (Monsanto #8322554 and #8322555) 5 c o n sistin g of 2 pages; E x h ib it #173 (Monsanto 6 #8322905) consisting of 1 page; E xhibit 7 #174 (Monsanto #8331219) co n sistin g of 1 8 page; E x h ib it #175 (Monsanto #8326231) con 9 s is tin g of 1 page; E x h ib it #176 (Monsanto 10 #233610 th ro u gh #233612) c o n s is tin g o f 3 n pages; E x h ib it #177 (Monsanto #233618 and 12 #233619) c o n s is tin g o f 2 p ag es; E x h ib it 13 #178 (M onsanto #231686 th ro u gh 231688) 14 c o n s is tin g o f 3 p ag es; E x h ib it #179 (Mon 15 sa n to #8321639 and #8321640) c o n s is tin g of 16 2 p ag es; E x h ib it #180 (M onsanto #8323058 17 th ro u g h #8323060) c o n s is tin g o f 3 pages; 18 E x h ib it #181 (M onsanto #232571 th ro u g h 19 #232574) c o n s is tin g o f 4 p ag es; E x h ib it 20 #182 (Monsanto #8323145 and #8323146) con 21 s i s t i n g o f 2 p ag es; E x h ib it #183 (M onsanto 22 #8323173 through #8323176)cons is tin g of 4 23 p ag es; E x h ib it #184 (M onsanto #233695) con s is tin g of 1 page; E x h ib it #185 (Monsanto #8323203 through #8323205) consisting of 3 JAMES MAY REPORTING SERVICE 1 2 3 C 8 9 10 11 .12 13 C U 15 16 17 18 19 20 .. 21 '.-22 V 23 24 25 pagas; E x h ib it #186 (Monsanto ,#8331253 th ro u g h #8331271) c o n s is tin g of 17 pages; E x h ib it #187 (Monsanto #8323177 and #8323178) co n sistin g of 2 pages; E x h ib it #188 (Monsanto #8323234 and #8323235) consisting of 2 pagas; E x h ib it #1S9 (Monsanto #235616 and #235623) c o n s is tin g of 2 p ages; E x h ib it #190 (Mon santo #8323245 through #6323248) co n sistin g of 4 pages; E x h ib it #191 (Monsanto #231738 and #231739)consisting of 2 pages ; E xhibit #192 (Monsanto #8321904 and #8321905) con s is tin g of 2 pages; E x h ib it #193 (Monsanto #231753 through #231756) co n sistin g of 4 pages; E x h ib it #194 (Monsanto #8323313 through #8323315) consisting of 3 pages; E x h ib it #195 (Monsanto #8323318 through #8323320) consisting of 3 pages; E xhibit #196 (Monsanto #8331273 and ,#8331274) con s is tin g of 2 pages; E x h ib it #197 (Monsanto #8323334 through #8323336) co n sistin g of 3 pages; E x h ib it #198 (Monsanto #8323340 through #8323342) consisting of 3 pages; E x h ib it #199 (Monsanto #8323354 through #8323356,) c o n sistin g of 3 pages; E x h ib it #200 (Monsanto #8323370 through #8323372) JAMES MAY REPORTING SERVICE concis ting of 3 pages; E xhibit #201 (Monsanto #236245 and 23 6246) cons is tin g o f 2 pages; E x h ib it ^202 (Monsanto #8323392 through #S323394) consisting of 3 pages; E xhibit #203 (Monsanto #236249, #236250, #236251 and #236252) consisting of 4 pages; E xhibit #204 (Monsanto #8331279 and #8331280) 2 pages; E xhibit #205 (Monsanto #8304330 through #8304385) consisting of 6 pages; Exhibit #206 (Monsanto: #230057 through #230061, and #8319596) co n sistin g of 6 pages; Ex h ib it #207, co n sistin g of 1 page; and E x h ib it #208 (Monsanto '#8323373 and #8323374, and #8323376) consisting of 3 pages. Q (By Mr. C alw ell) What is your name? A Clayton F. C a llis. Q How old a man a re you, D r. C a llis ? A 59. Q Why do th ey c a l l you d o cto r? A I have a Ph, D. Q What in? A Inorganic Chemistry. Q Where did you g et th a t Degree? A ^ U n iv e rs ity o f I l l i n o i s , Urbana-Cham paign. j> Q When d id you do th a t? JAMES MAY REPORTING SERVICE IN THE UNITED STATES DISTRICT COURT . SOUTHERN DISTRICT Op WEST VIRGINIA - CHARLESTC, WEST VIRGINIA JAMES M. ADKINS, Administrator ) of this Estata o f Ralph E. Adkins,) Deceased, at al, ) > )Plaintiffs, ) V*e ) MONSANTO COMPANY, a Dalawara ) Corporation, )) Defendant. ) )HO81-2098 Doposition of MONTE C. THRCDAHL taken on behalf of tba Plaintiffs. * * .* * * * Raporter: M. joy Springer J am es M ay R epo r tin g S e r v ic e CERTIFIED SHORTHAND REPORTERS H R . 2 - BOX 65 EOWAHOSVIU.E. ILLINOIS 62025 .n 1 M isso u ri, b efo re M. JOY SPRINGER, a N otary P u b lic w ith in 2 and for the County of Madison, S tate of I llin o is ; th at 3 the issuance of notice and dedimus is w aived, and th at 4 th is d e p o sitio n may be taken w ith th e same fo rc e and 5 effect as if a ll Federal ru les and statu to ry requirement: 6 had been complied w ith, 7 IT IS FURTHER STIPULATED AND AGREED th a t any 8 and a ll objections to a ll or any p art of th is deposition 9 except objections as to form of the questions'asked or 10 answ ers g iv en , a re hereby re se rv e d and may be ra is e d 11 on the t r i a l of th is cause; and th a t th e sig n a tu re of 12 the deponent is n o t w aived. 13 k'k'k 'k-k-kiT-k 14 15 16 17 18 MCNTE C. THRODAHL 19 produced, sworn and examined on b e h a lf of th e p l a i n t i f f s 20 deposes and says as follow s: 21 EXAMINATI CW 22 BY MR. CALWELL: 23 (Whereupon th e re p o r te r marked P la in 24 t i f f s D ep o sitio n E x h ib it #366 (Monsanto.. 25 #8322918, #8326238, #8323145, #8323146/' JAMES MAY REPORTING SERVICE y i #8323.203 through #8323205, #323234, #8323235, 2 #8323245 through #8323248, #236205 through 3 #236208, #236212 through #236215, #8323313 4 through #8323315, #8323318 through #8323320, 5 #8323334 through #8323336, #8323340 through 6 #8323342, #8323370 through #8323372, #8323392 7 through #8323394, #236245, #236246, #236249 8 through #236252, #8323748 through #8323751, 9 #8323831, #8323832, #235806 through #235808, 10 #8323866 th ro u gh #8323869, #8323876 through 11 #8323879, #8324039, #8324040, #8324170, 12 #8324171) c o n s is tin g o f 66 p ag es; E x h ib it 13 # 367 (Monsanto #8323075 through #8323079) 14 c o n s is tin g of 5 pages; E x h ib it #368 (M onsanto 15 #8326149 th ro u gh #8326160, #8326129 th ro u gh 16 #8326142) c o n s is tin g o f 26 pag es; E x h ib it 17 #369 (Monsanto ,#232571 through #232574) 18 c o n s is tin g .of ,4. pages; E x h ib it #370 (M onsanto 19 #233610 th rcu g h #233612) c o n s is tin g o f 3 pages; 20 E xhbit #371 (Monsanto #8305445, #8305446, 21 #8305443, #8305444, #8305441, #8305442, 22 #8305439, #8305440, #8306026, #8306025, 23 #8306023, #8306024, #8306022, #8306021,' 24 #8306020, #8306019, #8306018, . #8306017)' :` ` 25 c o n s is tin g o f 18 pages; E x h ib it #372'^(Mexi-* JAMES MAY REPORTING SERVICE *4 ;. . J m w // ' 1 2 santo #8306242, #8306243) consisting of 3 pages ; E xhibit #373 (Monsanto #8321750, 3 #8321751), consisting of 2 pages; E xhibit 4 #374 (Monsanto #236151 tnrough #235193) .for : 5 the purposes of id e n tific a tio n .) Q (By Mr. Calv7e l l ) Would you s ta te your 7 name, please. 8 A Monte C. Throdahl. 9 Q What is your ad d re ss, Mr, Throdahl? 10 A 36 B r i a r c l i f f , S t. L o u is, 63124. 11 Q And you*re o b v io u sly employed by t 12 M onsanto Company , is th a t rig h t? 13 A R ig h t. 14 Q And a re you a S enio r Vice P re sid e n t? ! 15 A T h a t's r i g h t . 16 Q I 'd lik e to ta lk to you f i r s t abouc 17 . your academ ic background. Where d id you go to school? 18 A How f a r back? ! 19 Q C o lle g e . | 20 A Iowa S ta te U n iv e rsity from *37 through 21 '4 1 - - t h a t 1 s 1937, n o t 18 -- Chem ical E n g in ee rin g . 22 Q Did you have an y p o st-g ra d u a te c o u rs e s 7 23 A Yeah. I had th e Advanced Management 24 Program a t H a.rv- ard B usiness S chool inry. 1960, ... ..... ; 25 Q O.k. Now, upon graduation'' from Towa - JAMES MAY REPORTING SERVICE *1 4 IN THE UNITED STATES DISTRICT COURT SOUTHERN DISTRICT OP WEST VIRGINIA CHARLESTON, VEST VIRGINIA JAMES M. ADKINS, Administrator of the Estate of Ralph E, Adkins, Deceased, et al, Plaintiffs, vs. MONSANTO COMPANY, a Delaware Corporation, Defendant. >))))) ) No. 81-2098 ))))) Deposition of FERDINAND C. METER taken on behalf of the plaintiffs. Reporter: M. Joy Springer J ames M ay R eporting S ervice CERTIFIED SHORTHAND REPORTERS 2R.R, - BOX G5 EDW AROSVILLE. ILLIN O IS 62025 l % .821 1 2 3 4 5 7 8 9 10 11 12 13 14 15 l 17 18 19 20 21 22 23 24 25 :.IN THE UNITED STATES DISTRICT COURT SOUTHERN DISTRICT OF WEST VIRGINIA 'CHARLESTON, WEST VIRGINIA JANES M. ADKINS, Administrator of the Estate of Ralph E. Adkins, Deceased, et al, P laintiffs, vs. MONSANTO COMPANY, a Delaware Corporation, Defendant. ))) No. 81-2098 APPEARANCES: M essrbsy. WC.a lSwteulal,rt MCcCa lowrmeilclk, J&r P. ,eyEtosnc,., M e"ssrbsy. BCohwarlleess, MM.cDLaovvide,, GI IrIa,ffE3sccL.,ove, For the P lain tiffs; For the Defendant. IT IS STIPULATED AND AGREED by and betw een counsel fo r the p la in tiffs and counsel for the defendant th a t th e d e p o s itio n o f FERDINAND C. MEYER may be ta k e n pursuant to Rule 26(a) of the Federal Rules of C iv il Pro cedure, on b e h a lf of the p la in tif f s , on Ju ly 6, 1983, a t .th e R adisson H o te l, Room 215, 9th S tr e e t and C onvention P la z a , S t. L o u is, M isso u ri, b e fo re M. JOY SPRINGER a Notary Fublic w ithin and fo r the County of Madison, S tate JAMES MAY REPORTING SERVICE , three pages; P la in tiff's Deposition exhibit #253 (M onsanto's I.D . #8323245 through 8323248, in clu siv e), consisting of four pages; P la in tif f 's D eposition E xhibit #254 (M onsanto's I.D . #231728 through 231737, in clu siv e ), con sistin g of ten pages; P la in tiff's D eposition E xhibit #255 (M onsanto's I.D . #8323234 and 8323235), c o n sistin g of two pages; P l a i n t i f f 's D eposition E xhibit #256 (M onsanto's I.D . #8323217 through S323219, in c lu siv e ), consisting...*of three pages; P la in tiff's Deposition Exhibit -257 (M onsanto' s I.D . #8323177 and 8323178), c o n sistin g o f two pages; P l a i n t i f f 's D eposition E xhibit *253 (M onsanto's I.D . #233695), con sis tin g of one page; P la in tif f 's D eposition E xhibit #259 (M onsanto's I.D . #8323203 through 8323205, In clu siv e), consisting of three -pages; P la in tif f 's -D eposition E xhibit #260 ('M onsanto's I.D . #8323173, 8323174, 8323176 and 8323175), consisting of four pages; P la in tiff's D eposition E xhibit #26l (M onsanto's I.D . #8323145 and 8323146), c o n sistin g of two pages; P l a i n t i f f 's D e p o sitio n #262 *(M onsanto' s I.D . #8323065 through 8323370, in clu siv e), consisting of six pages; P la in t if f 's D eposition E x h ib it #263 JAM ES MAY REPORTING SERVICE 1 (M onsanto's I.D . #8323037 and 8323038), con 2 s is tin g of two pages: P la in t if f 's D eposition 3 E x h ib it #26*1 (M onsanto's I.D . #231636 th ro u g h 4 321688, in clu siv e), consisting of three pages; 5 P l a i n t i f f 's D ep o sitio n E x h ib it #265 (M onsanto's 6 I.D . #83231^7 through 83231^9, in clu siv e), con 7 sistin g of three pages; P la in tiff's D eposition 3 E x h ib it #266 (M onsanto's I.D . #8330067 and 9 8330068), c o n sistin g o f two pages; P l a i n t i f f s 10 D e p o sitio n E x h ib it #267 (M onsanto's I.D . #8331208 11 8331209), c o n s is tin g o f two p ag es; P l a i n t i f f s 12 D ep o sitio n E x h ib it #268 (M onsanto's I.D . #8331208 13 and 8331209), c o n s is tin g o f two p ag es; P l a i n t i f f s 14 D ep o sitio n E x h ib it #269 (M onsanto's I.D . #832238*0 , 15 c o n s is tin g o f one p ag e; P l a i n t i f f s D e p o sitio n 16 E x h ib it #270 (M onsanto's I.D . #8330036), con 17 s i s t i n g o f one page; P l a i n t i f f s D ep o sitio n 18 E x h ib it #271 (.M onsanto's I.D . #236066 th ro u g h 19 236069, I n c lu s iv e ) , c o n s is tin g o f fo u r p a g e s; 20 P l a i n t i f f 's D eposition E x h ib it #272 (M onsanto's 21 I.D . #236065) , c o n s is tin g o f one page; P l a i n t i f f s 22 D e p o sitio n E x h ib it #273 (M onsanto's I.D . #8325873, 23 832587*1 and 8325872) , c o n s is tin g o f th r e e p a g e s; 24 P l a i n t i f f s D e p o sitio n E x h ib it #27*1 (M o n san to 's 25 I.D . #236180 and 236181) , c o n s is tin g o f two p ag e s; I iJ a m e s ' m a y r e p o r t i n g s e r v i c e Plaintiff's Deoosition Exhibit #275 (Monsanto's I.D.. #8326129 through 83251*42 , inclusive, and #83261*49 through 8 3 2 6 1 6 0 , inclusive), consisting of twenty-six pages; Plaintiff's Deposition Exhibit #276 (Monsanto's I.D. .#8331279 and 8331280), consisting of two pages; Plaintiff's Deposition Exhibit #277 (Monsanto's I.D. .#235680) consisting of one page; Plaintiff's Deoosition Exhibit -273 (Monsanto's I.D. *2362*49 through- 236252, inclusive), consisting of four pages; Plaintiff's Deposition Exhibit .#279 (Monsanto's I.D. *8323392 through 832339*4 , inclusive), con^ sisting of three pages;"Plaintiff's Deposition Exhibit *28l (Monsanto's I.D. #832 33*40 through 83233*42 , inclusive), consisting of three pages; Plaintiff's Deposition Exhibit #2c2 (Monsanto's I.D. #83331273 and 833127*4 ), consisting, of two pages; Plaintiff's Deposition Exhibit #283 (Monsanto's I.D. *8330781), consisting of one page; Plaintiff's Deposition Exhibit #28*4 (Monsanto's I.D. #8300999), consisting of one page; Plaintiff's Deposition Exhibit #285 (Monsanto's I.D. #8300998), consisting of one page; Plaintiff's Deposition Exhibit #286 (Monsanto's I.D. #832560*4), consisting of one "Plaintiff's Deoosition Exhibit #280 (Monsanto's JAMES MAY REPORTING SERVICE T.n /R????70 through 1n M us iv p ). con- 'page; P la in tif f 's D eposition E xhibit #287 (M onsanto's I.D . #8331712), co n sistin g of one page; and fin a lly , P la in tif f ' s D eposition E xhibit #288 (M onsanto's I.D . #8331272), con sis tin g of one page. , Q Would you s ta te your name, p lease? r A. F erd inan d C. Meyer. ( Q And where do you liv e ? > A. I liv e a t #18 R oclare Lane in Town and Country, M issouri, 63131. t Q. ' And a re you employed? 2 A No. I re tire d about th re e and a h a ir years 3 ago, February of 1980. 1 Q. R e tire d from Monsanto? 5 A Yes. 6 C. When you were employed by M onsanto, what 7 was your la s t Job w ith then? 8 A I was D irec to r of S p ecial P ro je c ts in the 9 Department of Medicine and Environm ental H ealth. 0 Q In S t. Louis? 1 A Yes . 2 Q Where did you a tte n d co lle g e? 3 A S h u rtleff College in A lton, Illin o is Q And what degree d id you re c e iv e ? 5 A A.3. JAMES MAY REPORTING SERVICE \f Monsanto LAW DEPARTMENT Monsanto Company 800 N. Lindbergh Boulevard Si. Louis. Missouri 63167 Phone: (314) 694-1000 March 16, 1990 Ms. Carol Van Strum 7493 E. Five Rivers Road Tidewater, Oregon 97390 Re: Mortality Studies of Nitro Plant Population Dear Ms. Van Strum: Please find enclosed copies of the two mortality studies referenced during our telephone call today. X have also enclosed for your review, copies of the trial record regarding Dr. Roush and Dr. Suskind which relate to those studies. I have also included in this packet a chart which was prepared during the trial to illustrate for the jury the statistical manipulation which was being undertaken by the plaintiffs' lawyer to artificially create the impression that there was an excess in cancer mortality at the Nitro Plant when as explained by both Dr. Roush and Dr. Suskind; the actual study data would lead to the opposite conclusion. If you have any further questions regarding this litigation or the matters addressed in this correspondence, please feel free to give me a call at (314) 694-2821. Sincerely, DFS/dlr E n c lo su re s CC: Dan Bishop w/o enclosures Telephone: CAROL VAN STRUM Science Writer 7493 East Five Rivers Road Tidewater# Oregon 97390 (503) 528--7151 Telefax:_____ (via voiceline) April 2, 1990 David Snlvely Law Department Monsanto Company 800 N. Lindbergh Boulevard St. Louis# Missouri 63167 Re: Information request Dear Mr. Snively: Thank you for the materials you sent from the Kemner case record. They are very informative# and I appreciate the trouble you took to copy them for me. Would it be possible for you to copy page 2 of the Monsanto Offer of Proof for me? It was missing from the copy of the Offer that I received. I also have a question about one document that puzzles me. The attached copy of Table 9 was stapled into the copy of the 1983 Zack and Gaffey study that you sent me# in front of page 586 (Table 9) of the study. There is no exhibit number on this page; is it part of some other document in the record of the Kemner case? I would be most grateful if you could send me a copy of the document it is from. Thank you again for your courtesy and help. Sincerely# CVS: cvs attachment Carol Van Strum *+tv- , i.V* - X-ff..w tJ'' ^iXnw VevtoUk**arvtlt r'*1 ^ c -* r "V,i ^ 4 tKUsCs<D.0.Z.-<Oeii.f>*c Hlo'M C r.t^ -H Table 9 Observed and Expected Humber Deaths During 1955-1977 by Cause and oofi _ 2,4,5-T Expoaure Category Showing Proportional Mortality Ratio (PHRs) -'xsV^.-- f' j t p J l & i i / (Hot Including Death! from TCP Incident) 1 Cauae of Death A11 cause* of death All malignant neoplasms Succal cavity and pharynx Digestive organa and peritoneum E xpoaed Observed Expected PHR 58 58.00 100 9 10.94 82 0 0.38 0 0 2.80 0 Hon -Expos e d Observed Expected PHR 89 69.00 100 v , 21 17.19 122 A 0.64 5.74 0 52 Stomach Liver All other digestive organs Respiratory system Lung 0 0.52 0 1 1L c 0 1.06 0 0 0.19 0 J > i n 0.39 0 : rx 0 2.09 0 4.29 70 6 3.78 159 s * * $ s k 4 5.58 72 6____ 3.57 168 4 5.26 76 All other respiratory organs D 0.21 0 0 0.39 0 Skin 0 0.29 0 0 0.35 0 Genitourinary orgsns 2 0.96 208 10 2.70 370* Bladder 2 0.22 909 7 0.65 1077* All other genitourinary organa 0 0.74 0 3 2.05 146 Lymphatic and hematopoietic tissue 0 1.35 0 1 2.07 48 Other sites Diseases of thenervous system and aense organa C^' 0 1.38 0.61 72 0 3 2.12 142 0 0.83 0 Diaeasea of thecirculatory oyatem 31 26.48 117 i52. 47.37 110 Arteriosclerotic heart disease, including CUD 27 19.72 137 43 33.63 128 All other diseases of thecirculatorysystem 4 6.76 59 9 15.66 57 Diseases of therespiratory system 2 2.67 75 4 6.49 62 Diseases of the digestive system 1 3.70 27 2 4.06 49 All other diseases ' 3 4.31 70 2 6.70 30 External causes of death 12 9.29 129 8 9.28 86 Hy analysis shoved 65 deaths. * P<.05 ixjCoatK. \ "Ha cpy i^* -- rt-Q\ 4 Monsanto Monsanto Company 800 N. Lindbergh Boulevard St. Louis, Missouri 63167 Phone: (314) 694-1000 April 11, 1990 LAW DEPARTMENT Carol Van Strum Science Writer 7493 East Five Rivers Road Tidewater, OR 97390 Re: Information Request Dear Ms. Van Strum: Thank you for your correspondence of April 2, 1990. Please find enclosed a copy of the missing page from Dr. Suskind's offer of proof. The other material which you referenced in your letter was inadvertently included with materials previously forwarded to your office. It is not a portion of a document in the court record of the Kemner case. To bring you current with the status of that case, I note that the Kemner appeal was argued last week by the parties. Monsanto remains confident that the verdict will be reversed when the decision is issued by the Illinois Appellate Court. Sincerely A:0FS-046.ch AO 88 (Rev. 1/94) Subpoena in a Civil Case EASTERN Issued by the UNITED STATES DISTRICT COURT DISTRICT OF MISSOURI WILLIAM R. GAFFEY _ V. PETER MONTAGUE and ENVIRONMENTAL RESEARCH FOUNDATION, INC. SUBPOENA IN A CIVIL CASE CASE NUMBER:1 91-193 8-6 -CES. TO: Dan R. Bishop. . 14796 Timber Bluff Drive St. Louis, MO 63017 I_I YOU ARE COMMANDED to appear in the United States District Court at the place, date, and time specified below to testify in the above case. PLACE OF TESTIMONY COURTROOM DATE AND TIME 0 YOU ARE COMMANDED to appear at the place, date, and time specified below to testify at the taking of a deposition in the above case. PLACE OF DEPOSITION Leritz, Plunkert & Brning, One City Centre, Suite 2001 St. Louis, MO 63101 DATE AND TIME October:-:31, 1994 9:30 a.m. 0 YOU ARE COMMANDED to produce and permit inspection and copying of the following documents or objects at the place, date, and time specified below (list documents or objects): See Attachment "A" PLACE Leritz, Plunkert SRBruning, One City Centre, Suite 2001 St. Louis, MO 63101 DATE AN D TIME October 31, 1994 9:30 a.m. 1 1YOU ARE COMMANDED to permit inspection of the following premises at the date and time specified below. PREMISES DATE AND TIME Any organization not a party to this suit that is subpoenaed for the taking of a deposition shall designate one or more officers, directors, or managing agents, or other persons who consent to testify on its behalf, and may set forth, for each on designated, the matters on which the person will testify. Federal Rules of Civil Procedure, 30(b )(6). IN 3 OFFICER SIG: (INDICATE F ATTORNEY FOR PLAINTIFF OR DEFENDANT) Attorney. frtEnvironmental ,Research Foundation, Inc. ISSUING OFFICER'S NAME. ADDRESS AND PHONE NUMBER Edward M. Roth, One City Centre, Suite 2001 St. Louis, MO 63101 (314)231-9600_______ (See Rule 45, Federal Rules of Civil Procedure, Parts C & D on Reverse) If action is pending in district other than district of issuance, state district under case number. DATE ,October-4, 1994 Il - I I AO B8 (Rev. 1/94)1 Subpoena In a Civil Case SERVED SERVED ON (PRINT NAME) SERVED BY (PRINT NAME) DATE PROOF OF SERVICE PLACE MANNER OF SERVICE TITLE DECLARATION OF SERVER I declare under penalty of perjury under the laws of the United States of America that the foregoing information contained in tie Proof of Service is true and correct. Executed on DATE SIGNATURE OF SERVER I 1I Rule 45, Federal Rules of Civil Procedure, Parts C & D: : li (c) PROJECTION OF PERSONS SUBJECT TO SUBPOENAS. (1) A party or an attorney responsible for the issuance and service of a subpoena shall take reasonable steps to avoid imposing undue burden or expense on a person subject to that subpoena. The court on behalf of which the subpoena was issued shall enforce this duty and impose upon the)parity or attorney in breach of this duty an appropriate sanction which piay include, but is not limited to, lost earnings and reasonable attorney's fee. (2) (A) A person commanded to produce and permit inspection and copying of designated books, papers, documents or tangible things, or inspection of premises need not appear in person at the plaice of production or inspection unless commanded to appear for deposition, heajjingjor trial. (B) Subject!) to paragraph (d )(2) of this rule, a person commanded to I produce and permit inspection and copying may, within 14 days aftej^ service of subpoena or before the time specified for compliance if such time is less than 14 days after service, serve upon the party off attorney designated in the subpoena written objection to inspection or copying of any or all of the designated materials or of the premises. If objection is made, the party serving the subpoena spall| not be entitled to inspect and copy materials or inspect the premises except pursuant to an order of the court by which the subpoena! w a s isstJed- If objection has been made, the party serving the subpoena m ay. upon notice to the person commanded to produce. m ove|at any time for an order to compel the production. Such an order tp compel production shall protect any person who is not a party or ap officer of a party from significant expense resulting from the inspection and copying commanded. (3), (A) On timely motion, the court by which a subpoena was issued shall quash or modify the subpoena if it ! (i) f^ilslto allow reasonable time for compliance; i (iij requires a person who is not a party or an officer of a party to travel to a' place more than 100 miles from the place where that person resides, is employed or regularly transacts business in ADDRESS OF SERVER person, except that, subject to the provisions of clause (c) (3) (B) (iii) of this rule. such a person may in order to attend trial be commanded to travel from any such place within the state in which the trial is held, or (iii) requires disclosure of privileged or other protected m atter and no exception or waiver applies, or (iv) subjects a person to undue burden. (B) If a subpoena (i) requires disclosure of a trade secret or. other confidential research, development, or commercial information, or (ij) requires disclosure of an unretained expert' s opinion or information not describing specific events or occurrences in dispute and resulting from the expert's study made not at the request of any party, or (iii) requires a person who is not a party or an officer of a party to incur substantial expense to travel more than 100 miles to attend trial, the court may, to protect a person subject to or affected by the subpoena, quash or modify the subpoena, or, if the party in whose behalf the subpoena is issued shows a substantial need for the testimony or material that cannot be otherwise met without undue hardship and assures that the person to whom the subpoena is addressed will be reasonably compensated, the court may order appearance or production only upon specified conditions. (d) DUTIES IN RESPONDING TO SUBPOENA. (1} A person responding to a subpoena to produce documents shall produce them as they are kept in the usual course of business or shall organize and label them to correspond with the categories in the demand. (2) When information subject to a subpoena is withheld on a claim that it is privileged or subject to protection as trial preparation materials, the claim shall be made expressly and shall be supported by a description of the nature of the documents, communications, or things not produced that is sufficient to enable the demanding party to contest the claim. ATTACHMENT A At the time and place set by the attached subpoena for your deposition to be taken, produce the following records for inspection and copying to the extent that you or your attorney have them in your possession, custody or control. 1. All documents constituting (a) minutes of meetings, (b) reports by or to or (c) communications from, to or among members or staff of the committee sometimes referred to as the "Nitro Health Study Task Force" which discuss or refer to any activiety contemplated or undertaken by the Task Force. 2. All documents discussing or referring to the creation, composition, organization, resources, mission, or purpose at any time of the committee sometimes referred to as the "Nitro Health Study Task Force." 3. All documents constituting or referring to press releases, "backgrounders," position papers, or public relations documents disseminated by any Person, including without limitation Monsanto Company or any chemical or paper industry trade or lobbying organization, to any Person, including without limitation any news organization, labor organization, medical association, governmental agency or governmental representative, or private public health agency, which discuss or refer to the Zack/Suskind or Zack/Gaffey studies or to the mortality experience at any time of any portion of the population of workers at Monsanto Company's Nitro, West Virginia plant exposed or potentially exposed to dioxin or other substances found in association therewith. 4. All documents constituting or referring to news or other media reports or accounts (including print and broadcast news media and scientific or public-health media) of the Zack/Gaffey study. 5. All documents constituting, discussing or referring to the presentation of the report of the Zack/Gaffey study at the 1981 International Dioxin Symposium, including documents actually presented at that conference. 6. All documents constituting, discussing or referring to public presentations., speeches or statements, or statements to the press by William R. Gaffey concerning (a) the mortality experience at any time of workers at Monsanto Company's Nitro, West Virginia plant exposed or potentially exposed to dioxin or other substances found in association therewith, including, without limitation, the presentation made by William R. Gaffey before the American Medical Association, Council on Scientific Affairs' Advisory Panel on Toxic Substances, 17 November 1983 and (b) other matters within the field of occupational or public health. 7. All documents discussing or referring to allegations of fraud, dishonesty, incompetence, or scientific inadequacy or irregularity in any of the Nitro worker studies or their authors, including, without limitation, all communications relating or referring to Dr. Cate Jenkins' allegations or comments regarding any of the Nitro Worker Studies performed by or for Monsanto Company. 8. All documents constituting, relating or referring to critiques, criticisms, reviews, or investigations of William R. Gaffey in connection with any of the Nitro worker studies. 9. All documents constituting, discussing or referring to Marcie Strauss's "Verbatim & Critique," including, without limitation, documents and communications used in its preparation and dissemination. 10. All attachments and materials that accompanied Marcie Strauss June 4, 1987 letter to Dr. Marilyn Fingerhut, a copy of which is appended as EXHIBIT "C" hereto. 11. All documents, including records of communications, which refer to this lawsuit, including, without limitation, any communications between William R. Gaffey and George Roush or any other Person. 12. All scholarly papers (reports, summaries, surveys, etc.) authored or co-authored by William R. Gaffey, whether ultimately published or unpublished. 13. All documents (including audio or video recordings, press reports, personal communications, etc.) discussing or referring in any way to William R. Gaffey's character or integrity. 14. William R. Gaffey's Monsanto Company personnel file and/or any documents known to have been placed in it at any time that are no longer in that file, including, without limitation, documents which discuss or refer to the reasons or purposes for which he was originally hired and subsequently employed by Monsanto Company and his job responsibilities at any time. 3 15. All documents relating or referring to the designation of William R. Gaffey as an expert witness in any litigation relating to dioxin, including in connection with the cases consolidated with and including Adkins e t . al v. Monsanto Company. 16. All documents which discuss, refer to or record the payment of money to William R. Gaffey since his retirement from Monsanto Company. 17. All documents constituting or referring to payments, directly or indirectly, by Monsanto Company, to the law firms of Coburn & Croft or Lewis, Rice & Fingersh or otherwise for the benefit of plaintiff William R. Gaffey in connection with this lawsuit, including without limitation agreements under which Monsanto, directly or indirectly, has paid legal fees to either Coburn & Croft or Lewis, Rice & Fingersh, reimbursed William R. Gaffey for such legal fees, or otherwise compensated or made payment to Gaffey or his attorneys for matters relating to this lawsuit, from the inception of the lawsuit to the present. 18. All documents marked for identification at the depositions in the cases consolidated with the including Adkins et. al v. Monsanto Company of Ferdinand C. Meyer, Monte C. Throdahl, Clayton F. Callis and William R. Gaffey, as indicated in part by the pages appended hereto and identified, collectively, as Exhibit "D". 19. Except to the extent already produced pursuant to the foregoing requests, all affidavits or transcripts (including, if available, notary certification page) of testimony (whether given at trial or deposition) by Judith Zack, Mary Gaffey, William Gaffey, Jan Yung, Raymond Suskind, George Roush, Clayton Callis, Monte Throdahl, Dan Bishop, and Ferdinand C. Meyer, together with copies of any 4 exhibits identified or discussed by or presented to such witnesses during testimony or in such affidavit. 20. All communications between William R. Gaffey and any Person discussing or referring to any of the Nitro studies. 21. All communications between Judith Zack and any Person relating or referring to any of the Nitro studies. 22. All reports of conclusions and analyses of the Zack/Gaffey study, including, without limitation, prior drafts of the study report finally published. 23. All proposals, contracts, study plans, rationales, protocols, progress reports, for the Zack/Suskind study or any antecedent study however denominated considered in its completion, whether completed or not, including any and all amendments, corrections, or other alterations to any of the foregoing, as well as all documents which refer to any of the foregoing. 24. All proposals, contracts, study plans, rationales, protocols, progress reports, for the Zack/Gaffey study or any antecedent study, however denominated, relied on or considered in the completion of the Zack/Gaffey study (whether such antecedent study was completed or not), including any and all amendments, corrections, or other alterations to any of the foregoing, as well as all documents which refer to any of the foregoing. 25. Except to the extent already produced in response to the foregoing requests numbered 22 through 24, all documents constituting or referring in any way to any and all epidemiologic studies, investigations, tests, etc., however denominated and whether actually completed, 5 & im partially completed, proposed, or hypothesized, that did or would examine in whole or in part the mortality experience at any time of the population of workers at Monsanto Company*s Nitro, West Virginia plant exposed or potentially exposed to dioxin or other substances found in association therewith, together with any control groups ("worker mortality studies"), including by way of example but without limitation (i) The Zack/Gaffey study, (ii) The Zack/Suskind study (iii) The study described in the published report of the Zack/Suskind Study as "an analysis of the chloracne cases and exposures not associated with this accident but rather with the normal TCP/2,4,5-T production processes"; (iv) The study performed by the National Institute for Occupational Safety & Health combining a Nitro worker population with populations from other plants and companies (including the, "Dioxin Registry Report" for the Nitro plant); (v) the workers' union study conducted by or through Mt. Sinai Hospital. 26. Except to the extent already produced in response to the foregoing requests numbered 22 through 25 above, for each such study responsive to the foregoing requests, all records constituting or referring to: (a) any and all proposals, study plans, rationales, contracts, classification criteria, protocols, drafts and progress reports ("study documents"), including for each such study document actual or suggested amendments or corrections thereto or critiques thereof; (b) any and all records generated as part of the effort to hypothesize, propose, justify, design, or perform each study; and (c) any and all records generated by, between, among, directed to, or received by each study participant or subject that discuss or refer to any such study in any manner, including all records of Monsanto Company's "Nitro Health Study Task Force." 6 X 27. All documents referring to the table and handwritten notes titled, "Table 9 Observed and Expected Number of Deaths during 1955-1977 by Cause and 2,4,5-T Exposure Category Showing Proportional Mortality Ratios (PMRs) (Not Including Deaths from TCP Incident)", a copy of which is appended as EXHIBIT "E" hereto. 28. All communications discussing, describing or referring to whether or not a follow up to the Zack/Suskind study should consist of an "analysis of the chloracne cases and exposures not associated with this 1949 accident but with the normal TCP/2,4,5-T production processes" as proposed in the Zack/Suskind study. 29. All communications discussing, describing or referring to the participation of William R. Gaffey in any of the Nitro Worker studies, including without limitation the participation of William R. Gaffey in any of the Nitro Worker studies during the period he was employed by Stanford Research Institute or other academic institution. 30. All communications discussing, describing, or referring to the actual or proposed participation of Raymond Suskind in what became know as the Zack/Gaffey study, including, without limitation, documents which refer to any decision to omit Raymond Suskind as a co-author of what became the Zack/Gaffey study. 31. All communications referring to any follow-up study (actual or contemplated) to the Zack/Suskind study concerning the mortality experience at any time of the population of workers at Monsanto Company's Nitro, West Virginia plant exposed or potentially exposed to dioxin or other substances found in association therewith, together with any control groups, including any communications to which Raymond Suskind, George Roush, Marcie Straus, Dan 7 & 3Wc Bishop, Ferdinand C. Meyer, Monte C. Therodahl, Clayton F. Callis or Richard Mahoney, members of the "Nitro Health Study Task Force," or representatives of the National Institute for Occupational Safety and Health, the Environmental Protection Agency, the United States Department of Justice, or any other agency of government (Federal, state or local) were participants or recipients. 32. All minutes of meetings of the Monsanto Company Board of Directors, Corporate Management Committee, Corporate Administrative Committee, any committee, task force, or other group created by or reporting to the Monsanto Company Board of Directors or any committee or subdivision thereof or any management-level group, which discuss or refer in any way to (a) any mortality study responsive to requests 1 through 4 above, (b) 2,4,5,-T, (c) trichlorophenol, (d) dioxin, (e) Agent Orange, (f) defendants in this action, (g) Rachel's Hazardous Waste News, including without limitation #171, (h) William R. Gaffey, or (i) Judith Zack, together with any reports or documents reviewed or considered by any of the foregoing committee's or groups or any of their members in preparation for, during or as a result of such topics being discussed, presented to or considered by any such committee or group. 33. All documents constituting or referring to communications between Dr. Raymond Suskind (or any person acting on behalf of Monsanto) and any Person concerning the position of the American Medical Association (or of any body affiliated therewith) on the hazards of dioxin. 34. All records that refer to studies responsive to requests numbered 22 through 24 above, including records of communications with the press or public officials or employees of public agencies, peer reviews, records of litigation, post-study records, and any and all records reviewing, criticizing, or otherwise discussing or referring 8 to the possibility of fraud, scientific irregularity or invalidity, inaccuracy, or incompetence in the conduct of each such study. 35. Except to the extent produced in response to any other request made herein, all documents constituting or referring to reviews, critiques or investigations of the Nitro Workers studies performed by Persons other than Monsanto employees, including without limitation, peer reviews and any investigations by the U.S. Environmental Protection Agency or other governmental agencies into matters relating to the Nitro worker studies, whether civil or criminal, actual or contemplated. 36. Except to the extent produced in response to any other request made herein, all documents constituting, discussing, or referring in any way to sampling and analyses of acnegens, dioxin, or other materials associated therewith at or near the Nitro plant, including but not limited to such efforts by Monsanto, the U.S. E.P.A., or any other entity, including (a) all sample plans, maps and other sampling site identification records, sample decoding information, protocols, sample handling and destruction records, laboratory communications, and analytical results; and (b) all affidavits or transcripts of testimony at trial or deposition, including all exhibits discussed or identified thereby, of all people who have testified in any case or proceeding about contamination of the Nitro plant premises with acnegens, dioxin, or other materials associated therewith. 37. Except to the extent produced in response to any other request made herein, all documents constituting, relating or referring to internal (Monsanto or Kettering) reviews, critiques or investigations of the Nitro worker studies, including, without limitation, investigations performed by Monsanto or any Person on behalf of Monsanto 9 ttv & into whether any or all of the Nitro worker studies were the product of fraud, dishonesty, incompetence or scientifically irregularity. 38. All documents discussing or referring in any way to any demand for retraction from Peter Montague of statements claimed to be defamatory. 39. All documents constituting or referring to any demand of retraction (actual or contemplated) of allegations of fraud or scientific inadequacy attributed to the Nitro worker studies or their authors, together with any such retraction actually made by any Person. 40. All documents which refer to the taking of any legal or public-relations action, actual or contemplated, against any person, other than defendants Peter Montague and Environmental Research Foundation, who published criticisms of the Nitro worker studies. II. DEFINITIONS AND INSTRUCTIONS Please interpret each of the preceding discovery requests in accordance with the following special definitions and instructions, as supplemented by the Federal Rules of Civil Procedure, the Federal Rules of Evidence, and jurisprudence thereunder; A. "Produce" means to produce any and all originals and any and all non-identical copies of the same document described in its or their most complete form, including, without limitation, any and all surviving portions thereof, and including any and all annexes, appendices, tabs, exhibits, indexes, cover sheets, transmittal letters, or other documents found attached to or 10 in the same file with the same document or documents, including without limitation, whenever available, the file identification and identification of the system of records in which each document and any and all copies are found. Wherever you are asked to produce affidavits or trial or deposition transcripts, also produce any and all exhibits thereto. B. The words "document" or "record" shall have the same interpretation as "documents or other things" within the meaning of Fed. R. Civ. P. 34, and shall also include all drafts, alterations, modifications, changes or amendments thereof. C. The term "person" or "persons" includes not only natural persons, but also all forms or organizations including without limitation unincorporated associations partnerships, corporations, joint ventures, proprietorships, firms, syndicates, and all subsidiaries, affiliates, divisions, departments, branches or other units thereof. D. The term "communication" refers to any written or oral transmission of information, belief or opinion, including any correspondence, letters, telegraphs, telexes, notes, memoranda, reports, circulars, press releases, discussions or conversations. E. The connectives "and" and "or" shall be construed either disjunctively or conjunctively or both as necessary to bring within the scope of the discovery request all records that might otherwise be construed to be outside of its scope. F. Where words or terms are not defined, they shall be given their common and accustomed meaning within the context stated. 11 G. The words "dioxin or "dioxins" mean any or all of the congeners, homologues, or isomers of the monothrough poly- chlorinated classes of dibenzo-p-dioxins or dibenzofurans. H. For purposes of this discovery request, the words "dioxin" or "dioxins" shall also include 2,4,5-T and trichlorothenol or any waste byproducts thereof. I. The phrase "Zack/Gaffey study" shall encompass the final published report of the purported study exhibited hereto as EXHIBIT "A", as well as other study designs or results contemplated, performed, or generated as a follow-up mortality study to the Zack/Suskind study. J. The phrase "Zack/Suskind study" shall encompass the final published report of the purported study exhibited hereto as EXHIBIT "B", as well as other study designs or results contemplated, performed, or generated in connection with that study as finally published, irrespective of whether such designs or results were incorporated in the study as finally published. K. The phrase "Nitro worker studies" shall encompass not only the Zack/Gaffey study, and the Zack/Suskind study but also any or all other epidemiologic studies, investigations, tests, etc., however denominated and whether actually completed, partially completed, proposed, or hypothesized, that did or would examine in whole or in part the mortality experience at any time of the population of workers at Monsanto Company's Nitro, West Virginia plant exposed or potentially exposed to dioxin or other substances found in association therewith, together with any control groupsepidemiologic studies. L. The term "Monsanto Company" shall encompass Monsanto Company together with all subsidiaries and, divisions thereof. 12 Library of Congress Cataloging in Publication Data Mam antry under fcflo* Human and envronmenlal risks ot crilonnated dioxns and related compounds (Environmental science research: v. 26] Proceedings ot an international symposium on ChJonnated Dioxin* and Related Com* pounds, held October 2 6 --2 9 . 1981 in Arlington. Va. Includes bibltograorucal references and inaex I.Tetrachlocodibenzodioxin-- Environmental asDects--Congresses. 2. Tetmchloro <S>eniDdioxir>--Toxicology--Congresses. I. Tucker, Richard E . U. Young. Aivm L. Ul Gray. Allan P. IV. Sen es. OH545.P4H85 1982 6 6 1 '.8 B 1 5 B2-18121 ISBN 0-306*41170-9 Proceedings ot an international symposium on Chlorinated Dioxins and Related Compounds, held October 2 5 - 2 9 . 1981, In Arlington. Vrgima 0 1883 Plenum Press. New York A Division ot Plenum Publishing Corporation 2 3 3 Spong Street. New YorX. N.Y. 1 0 0 1 3 AX rights reserved No pari ol this book may be reproduced, stored m a retrieval system, or transmitted In any form or py any means, electronic, mechanical, ohatocopying. microfilming, recording, or otherwise, without written permission from the Publisher Printed in the United States ot America PREFACE A lla n M , K . */ f ii./. EIS^ Increasing international concern is being expressed regarding the contamination of the environnent with polychlorinated rii`oenzo-pdioxins (PCDDs) and polychlorinated dibenzorurans because certain of these chemicals have been shown to be highly toxic to animals and are ubiquitous in the environnent. They are known to be distributee as contaminants of commercial products and as by-products froo com bustion processes. . A considerable volume of information has accumulated on these chemicals in the past two decades, particularly for the most toxic of then, 2,3,7,8-tetraehlorodibenzo-p-dioxin (2,3,7,8-TCDD). However, this body of knowledge has not succeeded in resolving genuine judgmental differences anong experts in the field as c d the degree of hazard to human health and the environnent. In licht of the widespread public concern, it is clearly imperative to come to grips with the continuing scientific controversy, to review the data, assess the issues, to see where areas of agreement exist, and where further research is needed to resolve renaining areas of disagree- *' ment. This volume represents an effort to contribute to these goals. The volume contains the Proceedings from an International Symposium on Chlorinated Dioxins and Related Compounds which was held October25 to 29, 1981, in Arlington, Virginia. The objectives of the- meet ing were to bring together scientists from a wide range of disci- plines, all of whom were directly concerned with one aspect or' another of the dioxin problem, to review the existing information, evaluate controversial data, present new data, identify areas of agreement, and indicate directions for future research. The 56 papers and-panel reports that comprise this volume testify to the success of'the Symposium. The meeting was divided into nine sections: Definition of the Problem Analytical Chemistry Environmental Chemistry Animal Toxicology v LINDA FALL DRAJS C* y i i/1 1 U ' * i n i < i t O C f f n OX-* A jp s fW / A) 57S^'^/C 1 A MORTALITY STUDY OF WORKERS EMPLOYED AT THE HONSAKTO COMPANY PLANT IN NITRO, VEST VIRGINIA Judith A. Zack and William R. Gaffey Monsanto Company St. Louis, Missouri USA BACKGROUND The compound 2 , 3,7,8-tetrachlorodibenzo-p-- dioxin (TCDD) is a highly toxic impurity that is formed in trace quantities during the production of 2,4,5-trichlorophenoxyacetic acid (2,4,,5-T). Exposure to TCDD can cause chloracne, a skin disorder characterized by comedones, cysts, and abscesses.1 Outbreaks of chloracne have been reported anong workers associated with the production of 2,4.5-T and 2,4,5-T based products. Such incidents resulting from beth accidents and routine occupational exposures have been reported from several countries. 2 The first reported industrial accident involving exposure to TCDD occurred in 1949 at the Monsanto Company plant in Nitro, West Virginia. A total of 122 employees developed symptoms of chloracne following a tri'chlorophenol (TCP) process accident. An undetermined number of other employees developed symptoms of chloracne resulting from exposure to the regular operations concerned with 2,4,5-T pro duction over the period 1948-1969. Between-1949 and 1953, Ashe and Suskind^*1* examined thirtyeight Nitro plant employees with chloracne. Twelve of these had developed symptoms of chloracne directly following the 1949 TCP acci dent; twenty-six other chloracne cases had resulted from exposure to Che regular 2,4,5-T production operations. In addition to chloracne. other signs and symptoms were observed in this group. These included severe aches in the lower extremities, fatigue, nervousness and irritability, loss or decrease of libido, dyspnia, and vertigo. These findings are consistent with those that have been reported in. other industrial incidents.w 575 PI i 3 '>> 576 J. a .z a c k a n d \v .r g a f f ; To examine the chronic health effects of exposure to TCD2, a mortality study of the Nitro plant employees vho had developed symptoms of chloracne following the 1949 TCP accident vas concucti The study cohort was comprised of 121 of the 122 chloracne cases; one female who vas living as of the endpoint of the study vas exc: from analysis. At the tine of the incident, it was assumed that t synptoms were caused by exposure to unknown products of decocpcsit From today's vantage point, these symptoms suggest exposure to TCE The 121-member study cohort, vith a presumptive high-peak exposure to TCDD, vas followed for mortality through 1978. The entire echo ; vas traced: thirty-two deaths were observed and eighty-nine person were confirmed as living. Analysis indicated no excess in total mortality or in deaths from malignant neoplasms. 1 The study presented here examines the nortality of Nitro plan j workers vho were assigned to an area of TCP or 2,4,5-T production, j vith potential for exposure to TCDD. The mortality of these vorke is examined in the context of the nortality experience of the tota I Nitro plant worker population. 1 The Monsanto Nitro plant began operations in 1922, vhen the j 'Rubber Service Laboratories purchased the plant as wa r surplus and began production of chemicals and additives for the growing rubber industry. In 1929, Monsanto Company purchased the Nitro plant ire: the Rubber Service Laboratories and entered the rubber chemicals business. Over the years, the Nitro plant has diversified to where it now produces agricultural chemicals, paper chemicals, plasticiz fine chemicals, and intermediates, in addition to rubber chemicals. The plant is* situated in the Kanawha River Valley, an area contain: one of the largest concentrations of chemical production facilitie: in the United States. i Of the many chemicals used over the years at the Nitro plant, i OQe has an established association with the occurrence of cancer ir ; man. Fara-aoinobiphenyl (PAB), used from 1941 through 1952 for use j as a rubber antioxidant and dye intermediate, vas shown in 1954 by I Walpole et al.7 to induce bladder cancer in dogs. In 1955, Nelick et al.e confirmed the carcinogenicity of para-aminobiphenyl to can i with the reporting of bladder tumors among workers exposed to this j chemical 'at two Monsanto plants, Para-aminobiphenyl vas produced a one plant and then transferred by tank car to the Nitro plant where additional processing vas carried out. The minimum duration cf exposure reported to have produced a bladder tumor is 133 days; the latent period has ranged from 15 to 35 years.9 An intensive screer ing program vas instituted at Monsanto Company about 1955 to exam ir on a continuing basis, all workers exposed to this chemical. Sever deaths from bladder cancer have occurred among Nitro plant employee enrolled in this program. These seven deaths are included in the present study. /iORTALfTY STU D Y OF W O RKERS E7? Other chemicals vith known health effects produced at the Nitre plant include methylparathion and carbon disulfide. The acute effect: of exposure to each of these chemicals have been described"**" vhile the chronic effects are less veil understood. Besides p-aninobipher.v! several other rubber chemicals are of potential health concern. For all of these, there is insufficient evidence to evaluate their carcin ogenicity to man. Tetramethyl thiuram disulfide is considered an animal carcinogen*1 and there is some evidence, although not suffi cient. that N-methyl-N,4-dinitrosaniline is also an animal carcin ogen.12 For several other rubber chemicals, there is insufficient evidence to evaluate the carcinogenicity to animals. However, these chemicals have the potential for fopning nitrosanines, certain of which are known animal carcinogens.1-3 Zinc dimethyl dirhiocarbamate. tetramethyl thiuram disulfide and tetramethyl thiuram monosulfide have the potential to form N-nitrosodimethylamine. N-Nicrosomorpholine has been found in product samples of 2 - (morpholinothio) benzothiazole and 4,4'-dithiodinorpholine (Frisone, G.J., The General Tire and Rubber Company, unpublished data). Although several of the chemical compounds produced or used at .the Nitro plant over the years have been associated with adverse health effects, no attempt has been made to relate chemical exposure to mortality vith the exception of decedents exposed to the TCP or 2,4,5-T operations and potentially exposed to TCDD. As a result, the only specific hypothesis that can be tested is whether a relation ship exists between potential TCDD exposure and proportional mortal ity, especially for malignant neoplasms. The mortality for this group is examined in addition to that of the total Nitro plant worker population. POPULATION AND HETHODS A study cohort was developed from the Nitro plant consisting of employees active on or after January 1, 1955 with one or more years of employment on the hourly roll prior to December 31, 1977. Salaried personnel who had never worked on the hourly roll were excluded from study because many of these employees had no appreciable exposure to the plant environment, and, for the most part, their exposure cannot be determined f.ron plant records. Females and non-white males were also excluded because of their small numbers. The cohort was assembled using government earnings reports, independent of the plant work history records. Annual earnings reports were available on a computer file from 1951 through 1977, Names and social security numbers were identified from this source. Work history records were used to supplement the earnings records. Information on race, sex, date of birth, date of hire, date of sepa ration, and, if deceased. 2,4,5-T exposure was abstracted from these records. Ascertainment of 2,4,5-- T exposure was confined to decedents only because it was too tedious to do for the entire cohort- The '7 8 J. A. 2 A C K A N D W . R. G AFFEY information from the work history records w a s used to determine which names identified from the annual earnings records net the cohort entrance criteria. Employees identified from the earnings records who terminated prior to 1955 were not included in this study because work history records for all such employees were not retained prior to this date. Exposure to 2,4,5-T vas determined by assignment to a 2,,5-T operation based on the work history records. 2,4,5-T exposure was determined for all but one decedent. Employees holding a job having plant-wide responsibilities with the potential for exposure to 2,4,5-T were, for the purposes of this study, considered to be nonexposed. The vital status of each member of the study cohort was deter mined using standard follow-up techniques and ascertained as of December 31, 1977. Death certificates were coded by an independent nosologist for the underlying cause of death, according to the rules of the Eighth Revision of the International Classification of Diseases, Adapted. Data for the total Nitro plant study population were analyzed by the modified life-table method using the U.S. population as the standard. With this method of analysis, the a g e - , r a c e - , time-, and cause-specific mortality rates for the U.S. general population are applied to the person-years lived classified by age, race, and time. A standardized mortality ratio (SMR) was calculated for 23 selected cause of death categories. Cause-specific SMR's for 15 selected cancer sites were calculated for subgroups of the total Nitro plant study population defined by date of death, age at death, and year of hire. The statistical significance of the deviation in a SMR from 100 was tested using the formula: standard error of SMR - 100 Vno- observed aeatns no. expected deaths If the observed SMR differed from 100 by 1.96 standard errors, it was regarded as significant at the 51 level. A SKR w a s tested for significance only when the observed number of deaths was five or greater.' Data for those deceased were also analyzed according to 2,4,5-T exposure using the proportional mortality method. In this case, the expected number of deaths is calculated on the basis of proportions of deaths observed in the U.S. general population. A proportional mortality ratio (PHR) was calculated for 23 selected cause-of-death categories. PMR's were calculated separately for those exposed to 2,4,5-T and for those not exposed. The statistical significance of the deviation of a PMR from 100 was tested by calculating the 952 M ORTALITY STUDY OF W ORKERS 579 confidence interval for Che FMR lur a given cause k according to the formula: confidence interval for PMR^ HCconfidence limits for 1 of observed deaths) where N number of observed deaths for all causes Both the standardized and proportional mortality analvses were conducted using the computer program developed by M o nson.1^ Tne observed mortality was compared to that of the United States white male population for the time period of study. RESULTS A total of 884 men were identified for study and traced for deaths through 1977. The entire cohort was successfully traced. Death certificates were obtained for all deaths. Seven hundred tvency-one (822) were verified as living and 163 (182) were confirmed dead by death certificates. _ ...... . . . . _____ . . . Tables 1-3 characterize the total Nitro plant study population by age at hire, year of hire, and length of employment. The dis tribution of the study population by age at hire indicates that the workers were fairly young at first hire (Table 1). Seventy-two percent of the study cohort were hired by age 30. None were hired at age 50 or above. Table 2 shows the distribution of the study population by year of hire. The majority of workers (75.32) were hired during the period 1940-1959, while smaller percentages of workers were hired prior to 1940 (10.82) and after 1960 (13.92). An examination of the study population by length of employment Indicates a fairly even distribution over the intervals less chan 10 years, 10-19 years, 20-29 years, and greater than 30 years (Table 3). Observed and expected deaths occurring during 1955-1977 among the total Nitro plant study population are shown by cause in Table 4. The SHR for all causes of death was 103 with 163 deaths observed and 158.10 expected. There were 35 deaths from malignant neoplasms with 30.92 expected, yielding a SHR of 113. Singificantly elevated SHR's were seen for the categories of malignant neoplasms of the genitourinary organs and of the bladder. The SHR for bladder cancer was 989 with 9 deaths observed and 0.91 expected. This excess in bladder cancer deaths is reflected in the elevated SHR for malignant nioplasms of the genitourinary organs. A significantly elevated SHR is also seen for arteriosclerotic heart disease. There were 79 deaths from this cause with 59.40 expected (SHR 133). The SHR for 6 8 0 J. A . Z A C K A N D W . R. G A F F E ' Table 1. Distribution of Total Hiero Fiant Study Population by Age at Hire Age at Hire <20 20-29 30-39 40-49 50+ Total Number 122 518 191 53 0 884 Percent 13.8 58.6 21.6 6.0 0.0 100.0 Table 2. Distribution of Total Nitro Plant Study Population " by Year of Hire " 11 * ** Year of Hire Humber Percent Prior to 1930 1930-1939 1940-1949 1950-1959 1960-1976 Total 21 74 361 30S 123 884 2.4 8.4 40.8 34.5 13.9 100.0 Table 3. Distribution of Total. Nitro Plant Study Population by Length of Employment Length of Employment (yrs .) Number Percent <10 10-19 20-29 30+ Total 225 213 204 242 884 25.5 24.1 23.1 27.4 * 100.1 Table 4, Observed and Expected Number of Deathf Standardized Mortality Ratios (SMR'S) Cause of Death All causes of death. All malignant neoplasms Buccal cavity and pharynx Digestive organs and peritoneum Stomach Liver All other digestive organs Respiratory system Lung All other respiratory organs Skin Genitourinary organa Bladder All other genitourinary organs Lymphatic and hematopoietic tissue Other sites Diseases of the nervous system and sense organs Diseases of the circulatory system Arteriosclerotic heart disease, Including CUD All other diseases of the circulatory system Diseases of the respiratory system Diseases of the digestive system All other diseases External causes of death_________________________ Number nt rTnEc: RBA Person-years nt risk: 1396R.7 *n < .01  'i % II luring 1955- 1977 by Cause Shoving >r Total Nitro Plant Study Population TCDA Codes 8th Rev. Observed Expected 140-209 140-149 150-159 151 155-156. -- 160-163 162-163 -- 172-173 185-109 108 -- 200-209 -- 320-389 390-458 410-413 -- 4 6 0 T 519 520-577 -- 800-998 163 158.10 35 30.92 0 1.03 4 8.65 1 1.63 0 0.60 3 6.42 14 10.51 14 9.91 0 0.60 0 0.58 12 3.75 9 0.91 3 2.84 1 3.15 4 3.25 0 1.28 92 82.59 79 59.40 13 23.19 6 9.13 5 8.03 5 10.46 20 15.69 SHR 103 113 0 46 61 0 47 133 141 0 0 320' 989* 106 32 123 2 o a > -< t/i H C o "C -n o * m 3J (a ) 0 111 133* 56* 66 62 4B* 177 Di CD 4 OOX J. A . 2 A C K A N D W . R. G A FFc other circulatory diseases was significantly low at 56. A signific deficit was also seen for the category of all other diseases where SHR was 4>8 with 5 deaths observed and 10.46 expected. Trends for malignant neoplaso deaths with calendar tine are sh In Table 5. SHR's which increased consistently over the period 155 ' 1977 are seen for the categories of all malignant neoplasms and ral > nant neoplasms of the respiratory system. The SHR for all maligr.an neoplasms rose from 32 to 131. The SHR for malignant neoplasms of respiratory system rose from 0 to 172 reflecting a SHR for lung can ' which increased from 0 to 181. Although based on very small number: the SHR for malignant neoplasms of the digestive organs and peritcm consistently decreased over tine from 99 to 24. The SHR for malign; neoplasms of the genitourinary organs peaked during the period 1501969. This is reflected in the SHR for bladder cancer which inerea; from 0 in 1955-1959 to a peak of 1471 in 1960-1969 and decreased to 833 in 1970-1977. The analysis of observed and expected deaths from malignant neo plasms by age at death revealed little in terms of consistent trends ' with age (Table 6). For nose of the cause-of-death categories, the SHR peaked at age 45-64 rather than continuing to rise with increzsi age. Bladder cancer is one category where the SHR remained high at age 65 and over. The distribution of deaths from malignant neoplasms by year cf hire is shown in Table 7. No deaths from malignant neoplasms were observed among workers hired after 1960. The SHR for all malignant neoplasms was similar for those hired prior to 1945 and for those hired in the period 1945-1959. The greatest difference in SHR's be tween those hired prior to 1945 and those hired from 1945-1959 occurs with bladder cancer. The SHR for bladder cancer is highest for those hired prior to 1945 with a SHR of 1111- A subset of deaths identified from the total Nitro plant study population was studied separately. Table 8 characterizes the deced ents according to 2,4,5-T exposure. Of the 163 decedents, 58 (35.62) were considered to be exposed to 2,4,5-T based on their work histcry records, while 104 (63.82) were considered to be non-exposed. The exposure of one decedent was unkovn. The results of the proportional mortality analysis by 2,4,5-T exposure classification are presented in Table 9. The proportion cf cancer deaths among 2,4,5-T workers is lower than in the non-exposed group (PHR: 82 vs. 122). The PKR for lung cancer deaths is slightly higher in the exposed group (PKR:_159 vs. 117). The proportion of deaths due to bladder cancer is higher among the decedents not ex posed to 2,4,5-T. There were 7 deaths from bladder cancer anong tr.es workers with 0.65 expected (PHR - 1077). The PHR for bladder cancer among decedents exposed to 2,4,5-T was 909 with 2 deaths observed and & m i I TAL1TY STU D Y OF WORKERS K Table 5. Observed and Expected Deaths from Halignant Neoplasms During 1955-1977 by Calendar Time Showing Standardized Mortality Ratios (SHR*S) for Total Nltro Plant Study Population 1955-1959 i Calendar Time 1960-1969 1970-1977 Cause of Death Observed Expected SHR Observed Expected SHR Observed Expected SHR All malignant neoplasms no1 3.13 32 13 11.81 21 15.98 131 Buccal cavity and pharynx 0 0.11 00 0.41 0 0 0.50 0 Digestive organa and peritoneum 1 1.01 99 2 3.48 57 1 4.16 24 Stomach 0 0.25 0 :0 0.70 0 1 0.69 145 Liver 0 0.09 0 i 0 0.28 0 0 0.23 0 All other digestive organs Respiratory system Lung 1 0.67 149 . 2 - o.ao0 0.117 0 04 0 ;4 2.50 3.83 3.59 80 104 111 0 10 10 3.24 5.B1 5.52 0 172 181 All other respiratory organa 0 0.07 0 :0 0.24 0 0 0.29 0 Skin Ccn1tourinary organs s0 0.07 0 0.33 00 0; 0.23 0 1.37 365 0 7 0.28 2.05 0 341 B )adder 0 0.09 0 5 0.34 11471* 4 0.48 033 All other genitourinary organs 0 0.24 00 1.03 0 3 1.57 191 Lymphatic and hematopoietic 0 0.40 0 '0 1.24 0 1 1.50 67 tissue _Otlior sites 0 0. 34 0 ! 2 1.25 160 2 1.68 119 *p < .05  I Table 6, i :i! Observed and Expected Deaths from Malignant Neoplasms During 1955-1977 b y Age at Death Shoving Standardized Mortality Ratios (SMR*S) for Total Nitro Plant Study Population cn > Cause of Death i : Age at Death <45 45-64 65+ Observed Expected SMR Observed Expected SMR Observed Expected SMR All malignant neoplasms 2 Buccal cavity and pharynx 0 Digestive organs and peritoneum 0 Stomach 0 Liver 0 All other digestive organa Respiratory system 0 0 Lung All other respiratory organs 0 0 Skin 0 Genitourinary organs 1 Bladder 1 All other genitourinary organs 0 Lymphatic and hematopoietic 0 tissue Other sites 1 *p < .05 2.39 0.06 0.51 0.10 0.03 . 0.38 0.54 0.51 0.03 0.13 0.20 0.02 0.18 0.55 0.40 84 21 0 1o 04 0 '1 0 1o 0 !3 0 ; 11 0 . ;n 0 0 0 \ :0 500 ; 3 :5000 : 2 0 l 0 !l 250 1 2 !a 16.85 0.67 4.53 0.85 0.32 3.41 6.36 5.99 0.37 0.31 1.4 3 0.39 1.04 1.60 125 0 87 118 0 88 173 184 0 0 210 513 96 63 1.90 105 12 0 0 0 0 0 3 3 0 0 8 6 2 0 1 11.69 0.31 3.57 0.68 0.24 2.65 3.61 3.42 0.19 0.14 2.12 0.50 1.62 1.00 103 0 0 0 0 0 83 88 0 0 377* 1200* 123 0 0.94 106 > N > n > z a $ o > AP m Table 7. Observed and Expected Deaths from Malignant Neoplasms During 1955-1977 by. Tear of Hire Showing Standardized Mortality Ratios (SMR'S) for Total Nltro Plant Study Population Cause of Death Observed Expected SMR Observed Expected SMR Observed Expected SMR All malignant neoplasms 25 Buccal cavity and pharynx 0 Digestive organs and peritoneum 2 Stomach 0 Liver 0 All other digestive organa 2 Respiratory system 10 Lun g 10 All other respiratory organa 0 Skin 0 Ccnitourinary organs 9 Bladder 8 All other genitourinary organa 1 Lymphatic and hematopoietic 1 tissue Other siteB 3 *p < .05 21.30 0.70 6.27 1.21 0.45 4.61 7.14 6.73 0.41 0.31 2.90 0.72 2.10 1.95 117 0 32 0 0 43 140 149 0 0 310* 1111* 46 51 2.03 148 10 ,0 2 1 :0 .1 4 4 io :o ;3 1 :2 1.0 ;l 8.63 0.31 2.19 0.39 0.14 1.66 3.09 2.93 0.16 0.22 0.76 0.18 0.5B 1.00 116 0 91 256 0 60 129 137 0 0 395 556 345 o 1.06 94 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0.99 0.03 0.19 0.03 0.01 0.15 0.27 0.26 0.01 0.05 0.09 0.01 0.08 0.20 0.16 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 5 n > H < iHn c D o tm37oS/CJ3) ) Table 8. 2,4,5-T Exposure Classification for Dccendcnts During 1955-1977 Among Total Nitro Plant Study Population 2,4,5-T Exposure Classification Number of Deaths Exposed Non-exposed Unknown Total 58 ' 104 t 163 Percent 35.6 63.8 0.6 100.0 I 1 aAk Table 9. I I Observed and Expected Number of Deaths During 1955-1977 by Cause and 2,4,5-T .Exposure Category Shoving Proportional Mortality Ratios (PHR'S) Cause of Death All malignant neoplasms Buccal cavity and pharynx Digestive organs and peritoneum Stomach Liver All other digestive organs Respiratory system Lung All other respiratory organs Skin Cenitourinary organs Bladder All other genitourinary organs Lymphatic and hematopoietic tissue Other sites Diseases of the nervouB system and sense organa Diseases of the circulatory system Arteriosclerotic heart disease, including ClfD All other diseases of the circulatory ay3tem Diseases of the respiratory system Diseases of the digestive system All other diseases F.xternnl causes of death Total number of deaths: *p < .05 2,4,5-T Exposure Category Exposed Non-exposed Observed Expected PMR Observed Expected PMR 9 0 0 0 o 0 6 6 0 0. 2 2' 0' 0\ i. 0 31 27 4 2 1 3 12 58 10.94 0.38 2.80 0.52 0.19 2.09 . 3.78 3.57 0.21 0.29 0.96 0.22 0.74 1.35 1.38 0.61 26.48 19.72 6.76 2.67 3.70 4.31 9.29 50.00 82 0 0 0 0 0 159 168 0 0 20B 909 0 0 72 0 117 137 59 75 27 70 129 25 0 3 0 0 3 8 8 0 0 10 7 3 1. 3 0 61 52 9 4 4 2 8 104 20.43 122 0.64 0 5.74 52 1.06 0 0.39 0 4.29 70 6.81 117 6.42 125 0.39 0 0.35 0 2.70 370* 0.65 1077* 2.05 146 2.07 48 2.12 142 0.83 0 55.34 110 39.68 131* 15.66 57 6.49 62 4.93 81 6.70 30 9.28 06 104.00 CwD O) J. A. Z A C K A N D W. R. G A F F E Y M O RTALITY STU D Y O f WORKERS 587 w.22 expected. PMR's for both exposure groups are quire similar for diseases of circulatory and respiratory system. Slight differences appear in the PMR's between the two groups for diseases of the diges tive system and all other diseases. However, the PMR's for both groups are quite low. The PMR for external causes of death is slightl' higher in the exposed group (PMR: 129 vs. 86). A listing of the cancer deaths among the 2,4,5-T exposed is given in Table 10. Table 11 listed the cancer deaths among the non-exposed group. DISCUSSION* The observation made many years ago of an apparent excess in bladder cancer among Nitro plant workers was confirmed and quantified in the mortality analysis of the total Nitro plant population presentee here. The SMR for bladder cancer was 989 and was the only statisti cally significant SMR among those for malignant neoplasms. The excess in mortality is not seen until 1960. The SMR peaked in the 1960`s and declined somewhat in the 19 7 0 's. The excess also appeared to be _ clustered in those decedents aged 65 years and older at death and in those hired prior to 1945. This would suggest that we should see a further decline in the SMR for bladder cancer over time. Although not statistically significant, the SMR for lung cancer appears to be elevated. The SMR increased with calendar time and was highest in those hired prior to 1945. The elevation appears to be clustered in those aged 45-64 years of age at death (SMR 184) and does not show a gradient with age. Further analyses to evaluate trends in lung cancer deaths as they relate to occupation cannot be carried out due to limitations in the'data collected in this study. The SMR for diseases of the circulatory system was elevated at 111. This is most likely a reflection of the higher mortality from heart disease which has been observed for Charleston, West Virginia and Kanawha County, Vest Virginia (unpublished data, Neas LM, 1979 and Enterline PE, 1979). For the total Nitro plant study population, there was a statistically significant excess In deaths from arterio sclerotic heart disease and a deficit In deaths from other circulatory diseases. This variation in the distribution of deaths from that of the U.S. may be due to risk factor or medical care differences in the plant population and the local area. These may include differences in smoking habits, th availability and use of medical services and the specificity of diagnoses. The proportional mortality analysis of decedents by 2,4,5-T exposure classification indicated no u n u s u a l 'patterns of mortality in the 2,4,5-T exposed. The proportional mortality ratio (PMR for malignant neoplasms was low (PMR * 82) in the exposed group. Lung cancer was rhe only site among the malignant neoplasms which was somewhat higher in the exposed group. II Table 10* Deaths Due to Hallgnhnt Neoplasms Among Nltro Plant Workers Exposed to 2,4,5-T oa 00 Year of Birth Year of Hire Year of lat Exposure Year of Te rm. Year of Death' Smoking HlBtory* Cause of Death as Given on Death Certificate 1917 1946 1951 1972 1972 : Cigarettes Carcinoma left lung with i mtastass (162.1) 1911 1948 1955 1972 1972 Cl garettes Metastatic carcinoma of the lung (162.1) 1916 1901 1911 1922 1923 1946 1944 1941 1945 1946 1959 1956 1948 1948 1950 1968 1963 1971 1972 1972 1968 j Cigarettes ! 1973 j Cigarettes 1 ;| 1975 ! Cigarettes 1 . ' 'i i 1973* j Non-omoker ! 1972 j Cigarettes 1902 1922 1948 1966 1966 ! Nn-'thkef \ti 1910 1944 1948 1968 1968 ; Non-smoker _____________________ , * Obtained by Interview with former coworkera of decedents. ** Included on the Nltro plant PAB rooter. I Bronchiogentc carcinoma o-f right upper lobe (162,1) Carcinoma lung with mtastases (162.1) Brnnchlogcnlc carcinoma with cerebral mtastass (162.1) Brnnchlogcnlc carcinoma with mtastass (162.1) General 1zed lipsameiw! (17U9i Metastatic carcinoma urinary bladder (1B8.0)** Carcinoma of the urinary bladder (188.0)** t, > S n > z o s I )1 / , I ! 1 Oft m Table 11. 1 Deaths Due to Malignant Neoplasms Among Nitro Plant Workers Not Exposed to 2 , 4 ,5-T Year of Birth Year of Hire Year of Termin. Year o f Death Smoking IIIstory* Cause of Death as Given on Death Certificate 1911 1945 1966 1968 Cigarettes Carcinoma of colon (153.8) 190V 1935 1957 1957 Cigarettes Carcinoma of liver (157.9) 1899 1929 1959 1960 Pipe Intraperitoneal carcinoma (158.9) 1905 ' 1944 1970 1972 Cigarettes Carcinoma of lung (162.1) 1909 1943 1962 1962 Cigarettes Carcinoma of left lung (162.1) 1910 1927 1966 1970 Cigarettes Pulmonary carcinoma (162.1) 1912 1944 1965 1965 Cigarettes Carcinoma of apex of right lung (162.1) 1915 1937 1977 1977 Cigarettes Carcinoma of lung (162.1) 1915 1939 1969 1970 Cigarettes Carcinoma of lungs (162.1)* 189 A 1944 1960 1964 Non-smoker Carcinoma of lung (162.1) 1912 1937 1973 1974 Cigarettes Carcinoma of lung (162.1) 1919 1946 1963 1964 Cigarettes Carcinoma of urinary bladder (18B.0)** 1901 1933 1962 1977 Cigarettes Carcinoma of bladder (188.0)** 1897 1941 1962 1965 Cigarettes Carcinoma of urinary bladder (188.0)** 1898 1933 1962 1965 Smoked years ago Carcinoma of urinary bladder (188.0)** 1905 1943 1971 1975 Cigarettes Carcinoma of bladder (188.0) 1898 1943 1963 1970 Cigarettes Bladder tumor (IB8.0)** 1QB8 1944 1956 1970 Unknown Carcinoma of bladder (188.0) 1905 1933 1969 1977 Cigars Pros'totic carcinoma (185.0) 1906 1946 1968 1977 Cigarettes Care 1noma of prostate (185.0) 1925 1945 1973 1974 Smoked years ago Carcinoma of prostate (185.0) 1919 1943 1972 1973 Cigarettes Hodgkin's Disease (201.0) 1901 1941 1964 1965 Cigars Osteosarcoma arising from left arm (170.4) 1901 1943 1966 1977 Cigarettes Carcinoma of liver 6 pancreas (197.8) 1922 1944 1964 1964 Cigarettes Adcnornrcinnmn (199.0) * Obtained by interview with former counrkcrs of decedents. ** Included on the Nitro pinnt TAB router. So 3H > -< CH/l C o o< T1 o? m*3) l3/1l ccnn CD E90 J- A. Z A C K A N D W . R. GAF The PHR analysis is limited in that an assessment of the toe; force of mortality cannot be made. The cause-specific PMR's onlvi approximate what an SMR analysis would have produced.16 The FXR i analysis presented here estimates the cause-specific risks associ with 2,4,5-T exposure and potential TCDD exposure. It is interesting to compare the results of this study of Ni plant workers potentially exposed to TCDD with the results of the study of Nitro workers involved in the 1949 TCP accident. The wo involved in that incident had presumed TCDD exposure as evidenced chloracne. The results of the two studies are similar in that ne shows an excess in deaths from any site among malignant neoplasms A recent study of Ott et al.17 found no excess in total core, or in deaths from malignant neoplasms among workers exposed to 2, These workers were probably exposed to very low levels of TCDD si: no cases of chloracne were observed. Other studies of workers uht developed chloracne resulting from TCDD exposure have been conduct and have been reviewed.6 At the present time, data from these va: studies do not constitute corroborative evidence of a cancer risk gum for any particular-cancer site. --------- -- -- *------- *-- -- REFERENCES *. j 1. Creig, J.B.: The toxicology of 2,3,7,8-tetTachlorodibenzo-p- dioxin and its structural analogues. Ann. Oc c u o . H v g . 22: 411-420, 1979. 2. International Agency for Research on Cancer: Long-term hazar of polychlorinated dibenzodioxins and polychlorinated diben furans. IARC Internal Technical Report No. 78/001. Lyon: IARC, 1978. 3. Ashe, W a n d Suskind, R - R . : Reports on chloracne cases, Konsanco Chemical Company, Nitro, West Virginia. Reports o the Kettering Laboratory, December 1949 and April 1950. 4. Suskind, R.R.: A clinical and environmental survey, Monsanto Chemical Company, NitrD, West Virginia. Report of the Kettering Laboratory, July 1953. J. International Agency for Research on Cancer. IARC Monographs the Evaluation of the Carcinogenic Risk of Chemicals to Man. Vol. 15. Some Fumigants, the Herbicides 2,4-D and 2,4,5-T, Chlorinated Dibenzodioxins and Miscellaneous Industrial Chemicals. Lyon: IARC, 1977. 6. Zack,'J.A. and Suskind, R . R . : The mortality experience of wor: i exposed to tetrachlorodibenzodioxin in trichlorophenol proct accident. J. Occup. Med. 22:11-14, 1980. i 7. Walpole, A.L., Williams, M.H., and Roberts, D.C.: Tumours of i urinary bladder in dogs after ingestion of 4-aminodiphenyl. Brit. J. Industr. Med. 11:105-109, 1954. M O R T A LIT Y S T U D Y OF W O RKERS 591 6 . Helick, W . F . : First reported cases of human bladder tumors due to a new carcinogen - xenylamine. J. Urol. 74:760-766, 1955 f 9. Helick, W.F., Naryka, J.J., and Delly, R.E.: Bladder cancer due to exposure to para-aminobiphenyl: a 17-year followup. J. Urol. 106:220-226, 1974. -------- 10. Key, M.H.: Ocuppacional Diseases: A Cuide to Their Recocniticn. U. S. Department of Health, Education and Welfare, Public Health Service, Center for Disease Control, National II Institute for Occupational Safety and Health. DHEW (NIOSH) i Publication No. 77-181. Washington: U.S. Government Printing Office, 1977. i; ii . H i* *1 :i I 'i 11. International Agency for Research on Cancer. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Vol. 12. Some Carbamates, Thiocarbamates, and Carbaziaes. Lyon: IARC, 1971. 12- International Agency for Research on Cancer. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. Vol. 1. Lyon: IARC, 1971. 13. Magee, F.N.,: N-nitroso compounds and related carcinogens. In: Searle, C.E.(ed): Chemical Carcinogens. Monograph 176. .......Washington: American Chemical Society, 1976. 14. Eighth Revision, International Classification of Diseases, Adapted for Use in the United States. U.S. Department of Health, Ed ucation, and Welfare, Public Health Service, PHS Publication No. 1693. Washington: U.S. Government Printing Office, 1977. 15. Monson, R . R . A n a l y s i s of relative survival and proportional mortality. Conput. Bioced. Res. 7:325:332, 1974. 16. Decoufle, P . , Thomas, T.H., and Pickle, L . W . : Comparison of the proportionate mortality ratio and standardization mortality ratio risk measures. Am- J. Epidemiol, 111:263-269, 1980. 17. Oct., G . , Holder, B. B . , and Olson, R . : A mortality analysis of employees engaged in the manufacture of 2,4,5-trichlorDphenoxyacetic acid- J. Occup. Med. 22:47-- 50, 1980. 9m Original Artie' > 22Volume . No. 1, January 1900 The Mortality Experience Journal ol Occupational Medicine January i960 Vol. 22 No. 1 of Workers Exposed to Tetrachlorodibenzodioxin in a Trichlorophenol Process Accident Judith A. Zack, and Raymond R. Suskind, M.D. A standardized m ortality analysis was conducted on edones. cysts, pustules, and abscesses. Hepatic dysfunc workers exposed to tetrachlorodibenzodioxin in a trichlo tion. peripheral neuritis, disorders or fat metabolism, and rophenol process accident at the Monsanto Company porphyria cutanea tarda are other frequently reported plant in Nitro. West Virginia. One hundred and twenty-one findings in these workers.1Chloracne has been shown to workers who developed chloracne resulting from this acci be essentially due to 2.3.7.S-tetrachlorodibenzodioxin dent on March 8,1949. were selected for study. Follow-up (TCDD).* a byproduct in the synthesis of 2.4,5-T. The sub o f this group was 1CQ% complete. The standardized mqr- ject of this paper isthe chronic health effects of exposure tality ratio for a ll causes o f death was shown to he 0.69, to TCDD. as reflected in the mortality experience of a w ith 32 deaths observed and 46.41 expected. For the cohort of Monsanto Company workers who developed categories o f malignant neoplasms and circulatory symptoms of chloracne following a trichlorophenol pro diseases, the standardized m ortality ratios were 1.00 and cess accident at the Nitro, West Virginia, plant m 1949. 0.68. respectively. Because o f the small size o f the cohort Production of trichlorophenol began in the fall of 1948 and the relatively small number o f deaths observed, the at the Nitro plant. In this process, the reactants results o f this study cannot be considered conclusive. 1,2.4,5-tetrachlorobenzene, sodium hydroxide, and However, it is important that no apparent excess in total methanol were all added to the autoclave. Heat was ap mortality or in deaths from malignant neoplasms or plied and, when the pressure reached the desired point, the diseases of the circulatory system was observed in a group autoclave was vented. O n March 8,1949, about sixmonths o f workers with a high peak exposure to tetrachforodiben- after production start-up. a violent reaction and decom zodioxin who were follow ed over a period o f nearly 30 position occurred when temperature and pressure within years. The'Tesuftt t f T f i l r s iu d i nill-lHi-ifrCCxporatcd widv--j the autoclave became excessive. The relief valve opened those o f a larger study whic/f\niT-7flOpde pkinCwork'ers ex - m and the fumes and tarry residues from the decomposed posed in the course of~Z4,5^hch!orbphenoxyaceticmacid ^contents of the autoclave were discharged into the at production during the period 1948 to:l969._ ` "~ mosphere and into the interior of the building. Employees who worked in the area of TCP production or were involved in the clean-up began to develop symp A wide variety of acute and sub-acute health effects toms immediately following exposure to the material has been reported inworkers involved in the manufacture which was discharged from the autoclave. Symptoms in of 2.4,5-trichlorophenoxvacetic acid .(2.4,5-T) from cluded eye and respiratory tract irritation, headache, diz 2,4,5-tflchlorophenol (TCP). The most consistent clinical ziness and nausea, and a severe irritant reaction of the ex finding ischloracne. a skin disease characterized by com- posed skin. After these initial symptoms subsided, the chloracne and other symptoms became evident. Ashe and Frofn Ih r D r o jitm r m o f M w iic in r jn d E n viro n m e n t! H e alth M o n u n io C o m p a n y. S00 N L in d b e rg h B lv d . Si L ou n. M O 6 J lb 6 [ M i Z ie L . tp id e m w Io g n tL Jnd the Im titu ir c l Environm ental Health, Kettering L a b o ra to ry, the U ru v e rm y o i C in c in n a ti M e d ic a l Center. C in c in n a ti. O H <S367 [O r Sul kind. D irector) Suskind1"* examined a total of 12 more severely affected workers on three occasions during the period of 1949 to 1953. Another 26 persons with chloracne, apparently not related to the accident, were also examined in 1953. The Journal of Occupational Medicine/Vol. 2 2 . N o . 1/January 1980 11 clinical symptoms, in order of relative frequency.* included acneform lesions: severe pains in muscles of upper and lower extremities, shoulders and thorax on exertion, fatigue: nervousness and irritability: decrease m Iihitio. dyspnea; vertigo and intolerance to cold On examination, all of the cases had chloracne Several were severely hyperpigmented. especially on the face. Of the six workers ex amined in 19*19 and 1950. four had liver enlargement and one had sensory loss m one foot. Liver impairment as in dicated bv hepatomegaly, tenderness and soreness in the right upper quadrant and epigastrium and a delayed pro thrombin time, was observed.11* In 1953, four of the six workers examined in 1949 and 1950 were re-examined and six additional workers involved in the accident were also examined. The findings in this later examination indicated a general regression of both the cutaneous and noncutaneous symptoms which had been present earlier. All of the workers showed a marked improvement in their skin lesions -- there were residua of the acne and a tew active lesions. In a few cases, workers continued to complain of aches and pains of the lower ex tremities and back, nervousness, excessive fatigue, and dyspnea. No clinical explanation for these complaints could be made based on the results of the physical ex amination.4 The findings of the examinations bv Ashe and Suskind are consistent with those which have been reported in other industrial episodes which occurred subsequently.' The acute health effects of TCDD exposure are described in the literature.7 but little is known of the chronic effects Several reports describe the occurrence of cancer and other deaths in workers exposed to TCDD which suggests an association between exposure and the subsequent development of a variety of neoplasms1" These reports, however, are generally of small groups of workers with relatively short periods of follow-up and are considered to be preliminary in nature. In a 25-year follow-up study. 17 deaths were observed among a cohort of 75 German workers who had been involved in a 1953 TCP process accident.* Of the 17 deaths observed (11-25 expected depending on the choice of a control population), six were from cancer (four or fewer expected), five from car diovascular disease (as expected), two from suicide (fewer than one expected), one from liver cirrhosis, one from a urogenital tract disease, and two from external causes. Of the six cancer deaths, three were from stomach cancer in the age group 6069, a number significantly higher than expected. Tw-o other cancer deaths were from oat-cell carcinoma of the lung and one was from adenocar cinoma of the colon. A similar accident occurred in the Netherlands in 1963 in a factory producing 2.4,5-T.* Eight deaths have been observed among 93 exposed workers. Five or six of these deaths were from cardiovascular disease. The proportion of deaths due to myocardial infarction was noted to be high. Jirasek et al* * and Pazderova" followed 55 of the 78 Czechoslovakian workers who were affected by chlor acne resulting from occupational exposure to 2,4.5-T and pentachlorophenol. In this study, five deaths were ob served. These included two deaths from bronchiogenic carcinoma (less than one expected), one from*cardiovas cular disease, one from liver cirrhosis, and one from an accidental industrial intoxication In 1976. a TCP process accident in Meda. Italy, resulted in the contamination of a large and densely populated area * A preliminary mortality study has been conducted in two of the 11 towns affected. The overall mortality rate did not differ from that expected, but increases in deaths from liver cirrhosis and leukemia were suggested. The chronic toxicity ot TCDD exposure to animals has been more extensively studied. TCDD toxicity has been thoroughly reviewed/ Chronic toxicity to TCDD is . manifested by liver necrosis, thymic atrophy, and deple tion of the lymphoid organs. Two studies indicate that chronic administration of low levels of TCDD to rats is associated with an increased incidence of neoplasia. In one study, the oral administration of TCDD produced an increase in hepatocellular carcinomas and squamous cell carcinomas of the lung, hard palate/nasal turbinates, or tongue.'* In another study, TCDD fed to rats produced tumors in 38% of the test animals.'* Neoplastic nodules and cholangiocarcinomas ot the liver were observed. The study reported here will examine the mortality ex perience of a cohort of 121 employees involved in jh e 1949 trichlorophenol process accident, with special em phasis on cardiovascular disease and on neoplasms, par ticularly of the stomach, liver, lung, and skin. Population and Methods In this study, the development of chloracne. a hallmark of TCDD exposure, was used to identify employees for study. The study population consists of all persons with chloracne which could be attributed to the 1949 TCP pro cess accident. Qne hundred and twenty-two employees who developed chloracne following this incident were -identified from plant safety records dating to the time of the accident, and from workmen's compensation and plant medical records. One hundred and twenty-one white males were included in this study -- one female who was living as of the endpoint of the study was not in cluded in this mortality analysis. It is assumed that all of the skin disorders recorded in the plant records represent true cases of chloracne and not other types of occupa tional or nonoccupational dermatitis. An analysis of the chloracne cases and exposures not associated with this accident but rather with the normal TCP/2.4.5-T produc tion processes will be the subject of a future paper. The data were analyzed by the modified life-table method using the updated Monson program.14 In this method of analysis, the ager. race-, time- and causespecific mortality rates for a standard population (in this case, the population of the United States) are applied to the person-years lived classified by age. race, and time. A standardized mortality ratio was calculated as the ratio of the observed deaths to the expected deaths for 22 selected causes of death. The statistical significance of differences between observed and expected numbers was based on the Poisson distribution and statistical signifi cance was determined at the 5% level of significance. For the purpose of analysis, each member of the study cohort was assumed to have entered the study on March 8. 1949. the date of the accident. The vital status of each member was determined using standard follow-up tech* >i^,traceTCTre^Tas^yZ)epenibeijLl-l-97L-Fj3r each 'jiersonTouhd to De 3eceSyed.'"a,death' eertificate was ob- 12 Mortality Experience of Workers Exposed to Tetrachlorodibenzodioxin/Zack and Suskind i m ! i m i n m u 11- Table 1. -- jbserved and Expected Deaths Among-121 Males Exposed to Tatradilorodibenzodioxin:. in a Trichlorophenol Process.Accident. : Caust IC D N o ! (Eighth Revision),' Observed i^ l* * Expected SMR Ail causes oi oeatn All malignant neoolasms : 140-209 32 9 16 41 9 .0 4 * - 0 .6 9 * 1 00 >3 Buccal cavily an d pharynx 'j* Digestive o rg an s and peritoneum S tom a cn % liver 140*1*491S-1S9 ia i 155-156 ` 0 0 0 0 0 30 2 .5 9 0 50 0 18 t 1 t t All other digestive organs Respiratory system --. I6QM 63 ** 0 5 1 91 3 02 * t 1.6 6 Lung 16 7.16 3 * ' 5 2 .8 5 1 .7 5 ATI other respiratory organs Skin 1 7 2 .1 7 3 *\ 0 I 0 .17 0 .15 '1 1 Genitourinary organs 185-189 0 1.16 t Lym phatic ana hematopoietic tissue F Other sites Diseases ot the nervous system and sense organs a Diseases oi the circulatory system 2 0 0 *2 0 9 " -- *: 3 2 0 -3 8 9 : 390*458 ) , ' 3 0 0 17 0 88 0 94 0 .3 6 25 01 1 1 1 : 0.6 8 Arteriosclerotic hean disease, including coronary hear) disease a Alt other disease o( the circulatory system Diseases ot tne respiratory system 4 10 *4 13 _ 460*519 *** 13 4 1 17 .7 4 7.2 7 2 .78 0 .73 B .t t Diseases oi tne digestive system All other diseases 520-577 1 . --. 0 2 2 .2 6 3 18 '* t : External causes ol death 800-998 3 3 78 . t 3 p < 0.05 t le s s m an 5 oosetveo deaths I tained. The underlying cause of death was coded to the hematoppietic tissue with 0.88 expected. - 8th Revision of the International Classification of There -were 17 observed deaths from circulatory Diseases, Adapted11 by an experienced nosologist. diseases wuh 25.01 expected. The standardized mortality ratio for circulatory diseases was low at 0.68. i Results All of the 121 members .of the study cohort were Case summaries for the cancer deaths are given in Table 2 .... , traced. Eighty-nine were verified living and 32 were verified deceased by death certificate. Discussion .. The results of the standardized mortality analysis of Because the study cohort was small and only 32 deaths the 121-member study cohort are shown in Table 1 The were observed, the results cannot be considered con standardized mortality ratio for all deaths is shown to be clusive. Nevertheless, the analysis of the mortality ex 0.69. with 32 observed deaths and 46.41 expected. This is perience of these workers indicated no apparent excess of the only statistically significant difference shown in this total mortality or of deaths due to malignant neoplasms table. There were nine deaths from malignant neoplasms or circulatory diseases. with 9.04 expected. There were no deaths from stomach The TCDD-exposed workers in the present study repre or liver cancer. There were five lung cancer deaths versus sent the largest group ever investigated after long-term 3,02 expected and one skin cancer death with 0.15 ex follow-up. The^fc^da_fot-inclusion.(presence of the ; pected. The malignant tumor was a fibrous histiocytoma workera*at- the subsequent occur- presumably of dermal origin, which is rare. There were renceofJchforaCheffipiifth e group to those with a signifi- * three deaths from neoplasms of lymphatic and canrexposure*at'that time. The latency period of 29 years Table 2. -- Cancer Deaths Among a Cohort of 121 Males Exposed to Tetrachlorodibenzodioxin in z Trichlorophenol Process Accident. Yur o( Birth Year ol Hire Year o( Death Death Certificate Statem ent ol Cause ot Death Sm oking H is to ry * 1909 1943 1962 Lung cancer (16 2 .1) Cigareiles s 1910 1911 1927 1939 1970 - 1964 Pulmonary carcinoma 1 1 6 2 .1 ) Broncmogenic carcinoma ( 1 6 2 .1 ) Cigarettes Cigareltes 1922 1945 1973 Broncmogemc carcinoma ( 1 6 2 .1 ) Monsmoker 1; 19 15 1939 1970 Lung cancer (16 2 .1) Cigarettes 1920 1946 1978 M alignant lib rcu s histiocytom a ol * Cigarettes soil tissue origin ( 1 7 3 .9 ) 1919 1907 1943 1943 1973 1971 H odg kin 's disease (2 0 1 .0 ) Lym phatic leukemia (2 0 4 .9 ) Cigarettes Pipe 1910 1939 1978 Acute myelogenous leukemia (2 Q 5 .Q ) ' Cigarettes ` Sm oking history w as oDlamed Dy interviews w iin former co-w orkers ot the decedents Journal of Occupational Medicine/Vol. 22 . No. 1 /January 1980 13 J1 M l H i t mb is longer than that of any pr us study, and the follow up is complete. Therefore, although the cohort is small, it represents the best opportunity so far to study the long term effects of TCDD on mortality. By augmenting these data with the results of comparable mortality studies, the long-term effects of TCDD may be more definitely evaluated. 7 h r authors *>n h lo lhanh M m M r tr l Yung, M r R jn d v Pk q Ip I. and M l Phyllis K o rir to r ih ru i t i n u i K r w ith the data co lle ctio n References 1 International Agency (or Research on Cancer IARC Monographs on the Evaluation ol the Carcinogenic Risk of Chemicals to Man Vol IS . Some Fumigants, the Herbicides 2,4*0 and 2,4.5-T, Chlorinated Dibenrodioxins and M iscellaneous Industrial Chemicals. Lyon. IARC. 1977 2. Kmmig 1 and Schulz KH Occupational acne (so-called chloracne) due to the chlorinated aromatic cyclic esters Permatologica n5S40-54t>. 1957 3. Ashe WF and Susktnd RR Reports on chloracne cases. Monsanto Chem ical Company. Nuro. West Virginia. Reports of the Kettering Laboratory. December 1949 and April 1950 4 Suskmd R R : A clinical and environmental survey. Monsanto Chemical Company. Nitro. W est Virginia. Report of the Kettering Laboratory. July 1953 5 Suskmd RR Chloracne and associated problems Report to the Conference of the National Institute ol Environmental Health Sciences on Chlorinated Oibenzodioxms and Dibenzofurans, April 3. 1973. b Suskmd RR oracnc and associated health prdblrm s in the manufacture of 2.-..J-T Rrport to the loml Conference. National lr> stitute ol Environmental Health Sciences International Agency for Research on Cancer. Lyon. France. January 11 1973 7 Young AL. Calcagm |A. Thalken C f. rt al The toxicology. en vironmrntal fate, and human risk associated with herbicide orange and its associated dioxin U S Air force O ccupational and lr> snronmental Health Laboratory Report O lH L TR-78-92. Brooks A.r Force Base. Texas. 1978 S International Agency lor Research on Cancer Long-term hazards ol polychlorinated dibenzodioxms and polvchlormaied dtberv zofurans IARC Internal Technical Report No 76/001. Lvon. 1976 9 Jirasek L, Kalensky |. and Kubec K Acne chlarina and porphyria cutanea tarda during the manufacture of herbicides Cesk Oermarof 48:306-317. 1973 10. Iirasek L. Kalensky I. Kubec K. et al Acne chlorma. porphyria cutanea tarda, and other mamlestations ol general poisoning during the m anufacture ol herbicides II Cesk Oermarof 49 145-157, 1974 11. Pazderova Lukas E. Nemcova M et al Chronic poisoning by chlorinated hydrocarbons formed m the production ol sodium 2.4.5-Irichlorophenoxyacetate Prac Lei 2b 332-339. 1974 12. Kociba R ). Keyes D C . Beyer ] f . et al Results of a rwo-vear chronic toxicity and oncogenicity study ol 2.3.7.8-tetrachlorodibenzo p-dioxin in rats T cucol A ppl Pharmacol 46 279,-303. 1978 13 Van M iller IP . Lalich | | . and Allen |R Increased incidence of neoplasms in rats exposed to low levels of 2.3.7.8-leirachlorodibenzop-dioxtn Chemosphere 6:537-544, 1977 14 Monson RR Analysts ol relative survival and proportional mor tality Comput Biomed Res 7 325-332. 1974 15 Eigth Revision. International Classilicalion ol Diseases. Adapted for Use in the United States U S . Department ol Health. Education and W elfare. Public Health Service. PHS Publication No 1693 Washington U S Government Printing O l (ice. 1977 14 Mortality Experience of Workers Exposed to Tetrachlorodibenzodioxin/Zack and Suskind 7 t /^ <b7 Human Health Effects of 2,4,5-T and Its Toxic Contaminants R. R. SuoWrK, M D, V, 8 . H o rtrbera, PtiO * A clin ical epidem iologic study w as conduct ad to d starm ln* tit long-term ha a 1th a ftacta of w orkp iece exp o sure to tha p ro ce ss of manufac turing tha h erbicid e (2,4,5*lrichlorophenoxy)ecetic a d d Including contami nants su ch aa 2 J3 l7 p&-IetrchlocodIbenxo-p-dlaxJn. The population conaUtad of two co h o rts; 204 claariy oxpoaad and 153 not axp oaad . Among tha axpoaad, ch n lcal evid en ce of chtoracrva p a rsla la d In 5 5 .7 % . Kona of tha not axpoaad experienced ehloracna developm ent. An a u o c U U o n w as found batwaan tha p ersistence of ehloracna and tha presence and severity of actinic ala ato sis of tha akin. Thara Is an association batw aan axposura and w a r atha history of gastrolntastlnal tract utcar. Pulmonary function value among thosa who axpoaad and who currantly sm oked w ere (owar than thosa who w ars not axpoaad and who cu rran tly sm o ked . Tha d ata aaaam blad In tha study Indicate no evid en ce of In cra a sa d risk for ca rd io va scu l ar dtsaasa, hepatic d laaaia, renal damaga, or cantral or paripharal nervous aystam problem *. (JLAMA 1064;251:2372-2380) THE HERBICIDE (2,4,5-trichloro- enced sente symptoms characterized phenoxyjacetic add (2,L5-T), first by skin, eye, and respiratory tract marketed in 1848, wxa used widely irritation, headache, dirtiness, and until 1870 in largo-ecalo farming, nausea. These symptoms subsided family gardens, forest management, within one to two weeks and wore and weed control along roadsides and followed by an acneform eruption, railroad rights-of-way. severe muscle pain affecting the * The medical and scientific commu extremities, thorax, and shoulders, nity was alerted to health problems fatigue, nervousness and irritability, arising from erpoaore to the manu dyspnea, complaint of decreased libi facturing process of 2,4^5-T following do, and intolerance to cold.' An exam a process accident (runaway reaction) ination of the worker* in 1849 that occurred in a plant In Nltro, revealed a ' severe and generalized ,,WVe, on March 8, 1949.' The accident involved a kettle in which tiielntcr-. 7 iacc"s"eefiTonsjngicemrumptt^io" np e(nehp hloerraacl~n*a)n,ehueriptiast^- mediate trichlorophenol was . being* . delayed prothrombin time, and In synthesized. Those employees In creased total serum lipid IsTela. By volved in the cleanup of the building 1953, those symptom* and findings and the repair of equipment expexi- Telcrfable to tha perron* ryatem and liver had subsided. Tbe chloracno, `'although much Improved, persisted.' of Eii it or-- Hm M, LW* In 1957, 2 A `IrS-holrach]rcxiibenxo- la Iw u * et h***ft,IU.Yu (jktxnevy0*0.M).SMS Owi p-dioxin (TCDD) waa identified a* a toxic and acnegenic contaminant of **. o * * . cm sx o r a> ow**Ka trichlorophenol synthesis.1 The *ub- acute effects of this agent, which have "Seen--Mr--e-p- eatedly observad in humans.' include chloracne,'>> the most consist ent clinical msrker, _Uver function impairment,1'1'* peripheral neuropathy.`A` nervousness and irritability.>J peraon-aii ty changes.111 porphyria cutanea_Larda,'`,J and hypertrichosis and Eype^pigmentaton.u', Elevation of levels of blood choleeterol.**'1 triglyc erides,' gamma-glutamyl transpgpLi- (GTh'J.1 and alkaline phospha tase have been reportedv Toxicologic studies of TODD in ani mals have revealed hepatotoxic ef fects,'*'0 teratogenic effects,'" * sup pression of cell-mediated immunity in mice and guinea pigs,11 and the induc tion of hepatic carona ms in rala," Some of the clinical reports have been concerned with the association of cardiovascular disease* and an Increased risk for cancar in popula tions exposed to TCDD.1,J>. Several comprehensive review* on this entire subject have been published.'*" A mortality analysis of worker* exposed to the runaway reaction materials was conducted. As of 1979, the Standardized Mortality Ratio (SMR) for all causes of death was 0.69, with 32 deaths observed and _4fi.AL erpectech_pDr_the_categoric* of cancer'and circulatory diseases, the SMRa were 1.00 and 0.68, respective ly.** A CLINICAL STUDY la Jan 1979, a clinical examination program was conducted that Deluded th adir and r*lir*d mploytea of th Nltro, WVa, plant, ho t n expoeed to th 2.4,5-T procesa between 1948 Lo 1969. Tha objectiva of th examination program waa 2 3 7 2 JLAMA, May 11, 1084-- Vot 251. Ko. 13 2.4.&-T--SuaUod A Hwtiberg 0 r 5h I V- } occhienppptibflpnlnotohoemureirloeyuacsaocnavrphliltdpltncrngntmeouuasleeseotir-oodrvlctnosto(fayreeyimessGanwtnmtodrer,isamrmloaiaehoasal)nartnisnToco,rlycieplc,dcn,,chh,rirfibdiieieeemodhsnaaaacpaamueretcclnpmaasseemsccnplcidoeinrrud.ocheitoaddsieu,dantatroiraailfrewditonacseabbrfdiresv,oaoipcnlooitmelliruthrglptkuioehpcprieswargdlenoaiumltrtilponhorudcosanloeyaaeercvtragfaefoukJerotseiinia..epnr2etrrvpssdtsxs,ttree4gehereepcncro,dotrouc5aosohaevcfeosn-tscuenneirerTfredetuirfcssoadhdspweositenesikspeaceolsnrx,dtsontrsLe.sepsU,ogsowerswd;oacvoiioTmaaocbsmeetinuenhehlcarrsioeifsklddeeeelesa-f,, S ubjects o f th Study ' ~jemptn-ttawnpaeto4trnwbeieh-|hxearlenxorro1nolcnaseoeaonsepvasc9Tantepnotsarisdicceollsoglhdwunpiykweurwmyswfns1lneud.rcsasuchwiauc3h1oamsaaheemiectrairl6set.sidhidlleitiueotsoe.a.emtleiosu:eeoditiftlendTuTTtecnearopfecwyxwbfomt1dhrshhlfllmip.oeo6o,jmaewi,oeebemeaoArtn1m3tyyoarnhrycleso9prueeelnemmaeotde4erosdmse1lsodka9muteuwo,eaei9hfwrnsbtemrrxib4weiaeaLi.nvlitxZen8apisjycroeitahqotetprOse.noahne4lolucntot'einadstvonn.hthsnt4saSooaunhaoeesfaeeoew1elg-tnIrdaecinTd9fnesfsy2lhu1cpcc,3riuyudiH,c9iiuumwhoen46sonbastibi6aaanre^n7icsiaissjhje9tlsrsosm5saleenepidenp;iau.sio-fwclcttfeb.TnnuetaduendettfeTcaltaynbstedom:ehedcTtlpnaymhdjiilypseh,cerdlemnhoaaec2eoloicaxlsgefrraal0edxpweodtliodepea4nnn2esn(epsrnuarmmse2,ostd,tssog;4cc,c)ww,wcedsisa,ttttfnaevs5ubiiudufhteeeoi(oonninhneeb-norru1icrvirrTnddndntod*eseeeeef)t, ctreeorcAnmoslrltidintsluai,vtteeinwdg,ecroaeehsmodparetslsotkeyeroedmefsi,nttoheaedcptiftavrareort,mgicreietpctaoisrtmeaemd.p,apTnoloyer - pltwiiieoo*arn*nas.ooinnanfolnltpethatlph,erootaissspcsetpiiubprdwlaoeynxhtoiLwsmo.veaOrroteaelfnuleytdnhxote6aem1mel%riiievrndeievndogpth:laueetrxhntipsutcaeosirlsp,eielaciyd-t Pmaartteiclyipa4t6e%d inofthtehestuldivyi,nags ndoidt aepxpproosxeid _ awtphbeeelrraseroufnofnonrarewal.npaaeTylrhysrgose,inasoncntaeilltyontwmhhme^orattitxnwelsire*^iraYeolsfde."txahptiaossasevtduaditlyo- Clinical Examination aWwdBnuliTodiTtrnhoihhfndeieugeirlripndinotlnf,tuahoeeWsterrimmvnVwwieaeead_Mwlslaisk"bpccoiaodJornnumadslftyeorpcanlrlecyit1ntt1eiaiwocdntnaeaolrlbeyae1ysxx8iaoa,smHmoo1niei9fodnt7bupaa9ltcta.oiittoooehiodndn. dganShUGwpcplGtnbLfl(tnnippmnCNwDMiiiinLeseareoeleCreenenmpolioGeroeaiegaroaLtarCtnDrrrrerivonorrOeesondwtvoavvfsantetdTcaeoriildpLerconldmteteneedsoiiTeaanetmgPeinrcdigrtd)ieco,eenllntdoior,iolmoaae,liofy'isayaacitcibc)aci,locntonfpletntSrsanl.colheouleatdasharrta,,iprisaeoGienoondlr,sadrilscma(lntCUlidnsiecacmodfbtandlhevsanPgEeoeinddre,epluriuudpeasiulelpTnelbsGmnratednanN(tymclomcfidmatvalsyshKita,cdtcbrtetGetcordtielootaeoEiioespatoilho,trpoeiDooafu.aind,utrerromnh)ubooyrbRt,ibrlynsntmi,cdLfhoilkyiaUneurrniupvodbnehgelenulo)santutfvimhbrovinlrsenodvem,elinualroxretaaeoycoowe,in,iseieru,lancotmilinamvcoablmysftlnhiunhbocd-rLboprelnpaevupIgdeorteyeectoicliocptlinrh,haoaliooonsne-thnuac*riilsopiatlceneh.lostboenento,tsoetsyaitu'ynnihayxtsomtdruniism,lPsdrP[sriweyodnau.lsnoatediitbtmL,auserestlnmfgusdimaesuecmcjyalyo,rirlit,peeebatigroruphmaoneocvesjne{dieecenhlhufeeinomncoeudloasVugerdataob,ocxacimddtsnapssilanscgsl,Cdhnigattauotdorocogtpotuan,shibiloamorf"hRrnirifoconultsnosiraiarn-oireliopenehsedteeeln/odebpedyminocmiiHribgaoc,nsblm,msnmt.ererodaifomulerlteuofa,nsedcemutoeiwgptremuaeulutTtbroalnoapiddirsbnieernuttonrtdeinrlrinoatothhtuhlechieliynutanidtnareicseesfytndlndhehnee**seael,-li,/,,.;, Analysis of Data usjvnpattmfupStweMfwptjSSarastuhohohiremesoaseunnpUatesyye'eesirerreccealrusrcsldsaDotssryomeutndvmediythtulikel.mnttfa'enkeitegit,eyaseervaniesvssnoxsioneTtpasfmmtegattane,rsce,anaoocaightiil,nhnlseghdscneolc.aamrueeeydeatl.fmtatlgctcrnawegoLxrhigisiepyiloll.DntpdsoztifrnpeoeeiaideacerfvamoadniunemoosrsiraianboadeftcrntdcilciAeegntiputuhomcynagnuoadtai*eagcrcdanaimqnenr.sislefldiNeruorpuonarlecnedauawTesenaraeutpsvavdtolsagngesorraienyerhheltealnuemseoesrdliertamdartfralsiraocbgdtdenynhvesormsfii,liebtaugaisrws,yeteomterhalnseolr)optboakddeasnvneeduecscporlasrklieseaaancrdsySdoeslaiaaubvuyuxixpettanlioasnnlnipttyfaauojalppro'ctoito.haioemgdsdupielsenurotucfsowruntdrwTuteemisrasnowshyorwelcdegtec'sinseesbrcodeiaeamlnbseetaedttrsiiahresncivalcnroanatannecvotlmfd"eehecaaraoanytftioodgonattdyuluc!lnotlneedsulmroryrMuyarucc.suaidncotam*ae.aavaislioiossfolepictutinunsnfcage.yutcideh*melscmatp(pnh.dysdudraeaA(sner,eaen'uriee'geen.,ieepbeldFapcesrerc-dscpwvdedsaobuatisuviwTaa)htiaveerntatuctlrritoenrnhehhheirhnabtdeaoeaeietytbersdhninddooeesssye-rs"rf,. qgitlscatandcaLuwtfayumiftnxiinhrhutaonuolbnrseapsoeeasgipoglarerneenmddrntaincoqteseodhdyudnccuoorelu.sepespestIic^xamrstiepteualsyMmaop.fcatclf5endraisiopotustihnmdhvenec0beudawamLanolgledylnrnsoroilcodtdflirconatee.ohtysrtrotegeaeoenohkvfaaiatreeuatsiotildtonfatmeeaccsenea-hbtipntjlldnnHftrtcocrdeiusaywinatesn.ceettcinweabasslos)naeogole,rftcngpLecrxigfmmeatarsntmoraeptasepoesenfshas.oesncptrtiuerggsxoscdaenzumrFdtaonrolsopryljgedpmeoreeicauactnoalltsoeissdsriwiodidnslstfohapnfrasaaiutjajgoipntieginetemtufbuenrairotnishrhraircdoeaheoslsbsann'odeereytsiprnttnalndynumgnmswsyrostgarsoigeoioparetmnsntebcfiexreoswwndsitugabmnfwsofnnhauopaugrsoenloe"ofctltppedoeciarrcytrrtrtpoqocsneuwtlfewhtmeseiefotilunutslxvisxoosexeamsumrpeattppea"peprntn*shpispnlolmesnuooto'deoea(hcmcpfuwlpnld<kssswyiimyefwtsluntaanmunioteSraeshsnhacroorlaedotrarkitds0oeoeyagskeeesft, RESULTS D em ograp hic Inform ation Demographic data of the 367 white males were examined to determine potentially confounding variables. The mean ages of the exposed and not exposed groups were 56.7x0.7 (X x S E ) years and 46.2x1.0 years, respectively (PC.OOOl). The two groups were found to be significantly different with respect to employment status and highest educational level achieved (P<.0001). In the exposed and not exposed groups, 34.8% and 13-5%* were retirees and 9.8% and 0.6% were terminated (left voluntari ly or laid off), respectively. Among the exposed and not exposed groups, 9.4% and 1.2% reached no further than the eighth grade, respectively; 72.4% and 56.8% had some high school education, respectively. Among the not exposed, 42.0% attended col lege, some to completion, while among the exposed, only lL2% attended college. * t -- Alcohol-and S m o k in g ----- -- -- ;-- History of alcohol consumption was not found to be significantly different in the two groups. When amoking status (current, former, or never) waa used as the criterion, no differences were found. Among current smokers, the exposed group had smoked signif icantly longer than the not exposed by 19 pack-years (,0001<P<.001). Among former imolcen, the exposed /""v, JAUA. Way I I .1 0 S 4 -- Vol 261, No. IQ 2,4.6-T -- SuskVvd & Hrtxb*m 2373  Toup hid smoked longer than the not xposed group by seven pack-years (.05</><.10). This reflected the tenyear age difference between the exposed and the not erposed group. H latory of M ed ical Problem s The comparison of the exposed and not exposed cohorts for self-re ported history of illness is given in Table 1. Chloracne was reported only in the exposed group; 86.3% in the erposed v 0.0% in the not exposed. The data about the history of ehlonacne were determined on the basis of statements from subjects that an acnelike erup tion called " weed bumps" appeared after an assignment to a 2,<t,S-T pro duction area. Records of the medical department of the company and the state Workmen's Compensation Bu reau stating that the person had chloracne confirmed many of these histories. In the not exposed group, a history of acne vulgaris was reported more frequently than in the erposed group. This information was based on the story of adolescent acne before employment at this plant. A history of upper GI tract ulcer was reported almost four times more frequently in the exposed group. When the medical history of the exposed and not erposed was compared for two age groups younger than SO years v SO years or older, a history of coronary artery disease and of hypertension were related to age, not exposure. Among the not exposed, angina was significantly related to age; in the history of upper GI tract ulcer, how ever, exposure, not age, appeared to be a factor. Closer examination of onset of ulcer in relation to exposure revealed six subjects whose symptoms oc curred before exposure. There were also four subjects whose symptoms occurred while they were receiving corticosteroid therapy or high doses of aspirin or that were attributed to. chronic alcoholism. If these ten sub jects were omitted from the analysis, there remained statistically signifi cant differences between the exposed and not exposed groups (16.6% v 5.5%; P ^ .0 1 on age adjustment). The complaint of loss of libido occurred more frequently in the exposed group than the not exposed group. When age was considered, the largest number of complaints of loss of libido or impotence were reported Tab* 1.-- Hulory of Madical Proclama v apoaur Slalua and by Apa *<ri g <00 rr. 'V lw a TT. X flllOTf * w Cjkpoa* No C.mri4 Cruari NeH tlooil (n-ao*t* (n-IJ (h- tOO| (-tes- CNoraenaf 1 M.3 00 76.3 0.0 SO.3 0.0 *arm u^guti|l^ 0.0 79.6 17.7 43.0 7J a.s Skjr>carte 3.0 3.3 0.0 1 0 S,3 4.6 H|i>non|a 34.S 3<S 31.8 .10.0 38.6 16.1 Aiv M 7.4 S.l 3.0 1.0 7 0 14.J Contwr t*ry io.a ai 3.0 0.0 iis 13.0 p C * oadrw*MiMl Erad Cari 30.7 3.3 13.7 3.0 710 6.4 Cano of al iAm 1* (un d aadrj ao U 0.0 0.0 10 " 12 " O " c4 IT 3 0 4 u t t M i cM rio o o n v ^ l * h i w v p f t y < J l u n n t i i m p ro g ra m b u l K ad a d o C u n o K a d a o i t n a n 'i e o m c im ih o n d a n toe e N o n o r , t ^ < . 0 0 0 l ; P *a A ja I V U * n i * - H a a n a t a l o o m p a n a o n o i c o t a i n a l a i p o i a d i g i r n a o a n a t a . 1.01<*<.06: n upoaad; TexoiJ r o*a. &yFtaht'a aaact l1 ano nlwni1 .0 0 1 < / * < , 1; P v a b j la r U a nial* Ha a n a al c o o t M iu o n H a a p o n i l t a b apa atraa. , . a < / v< . 1 0 : tu a r p o a a d . Toia-ig r o*d. bt F ia n " a u c a la a l. ^ IK .O O O I; n nol aip o aad . a oM . try F t i h a ' t a a a c l la a l. M OOI < P < , 0 1 n no a rp e a d. y o r g a o*d. b r F U r W a a a a c l la a l. * *Vi v aaooaad p ti . Haba anear, o-o: caln cano, Brraa; p ir u lo cinca*, na; n r a nM arponad orouo, bUbMr Canear, ora; m r inomi, cr. *.03</1<,10; * arpea i. 1.COKP<.OI: tor Itentai roung rod, by FWw* HaanaxWeompartaonof aapewatdna>t0. noatpoaad K Toaa pa HiU, t/^C.OOQt: Innoupoaad. r***j read, by FWw'a auo laat. t.OCn<PC.0l; Inaxcoaad. yoi*g rod, byFWrar1and laat. .OOOK/^.OOl; h arpo.ad. yard veM. by nww'a ucl laal. by the-older age group (Table 2). As noted in Table 1, the reported history of skin cancer, hypertension, angina, coronary artery disease, and cancer of all sites (except skin) was not foand to be significantly associ ated with exposure. The sample sire obtained was sufficient (at signifi cance level of .05, power of .80 (proba bility of detecting a true difference]) to detect a fourfold increase in skin cancer, a twofold Increase in hyper tension, a threefold increase in angi na and coronary artery disease, and a sixfold increase in cancer of all sites (except skin) for exposed over what was observed in the not exposed. As noted in Table 2, the complaint of nervousness/depression/anxiety and the complaint of impotence were not related to exposure. The aample aire was sufficient to detect a twofold increase in complaint of nervousness/ depression/anxiety for exposed over not exposed. Although the sample size was sufficient to detect crude differ ences between the two groups with respect to complaint of impotence, the difference disappeared when age was considered. The exposed population was catego rized into three subgroups, ie, those who never had chloracne develop (n"28), those who had a history of chloracne only *(ri"69), and those whose chloracne persisted ( " 1(77). When the histories of medical prob lems were examined in relation to chloracne status, hypertension and coronary artery diseaae.were found to be age related, not chloracne related. Histories of skin cancer and angina were not statistically significant when related to chloracne or to age within the chloracne groups. While it would seem (Table 3} that aida cancer 237 4 JAMA. May M . 1904-- Vol 2S1. No. 10 2.4t5.T--Suaklnd & T a t)!* 3 , -- H i lo ry o f M e d ic a l P fo O lo m i v C M g r tc n * S la lu a *n D o a d O n ly a nd b y A g * 'M l i l o r f ACM \AQAM 5tan tin e a * HyV*1v<UM t ArxprM C o rO A tfY >flOTY o*UpC--r g * t ro A H t in * l tract i lo a r Cane* al anaa (a a c a d ik n l h*Miory O nly (n -M J a.a 0.0 3S 3 5.0 S.S ie .3 44 Cunanl In -1 0 7 J oI..sa 38.3 10.3 ii a 35.2 3.9 Ho {-amH t a t o r y 13.0 34 107..00 3.S 14.3 00 C N o f K H Slalva, X fa alo r y Onty (n-1 8 ) ia a 0.0 0.3 0.0 e.3 S.S 00 A*a <SO |t Currant ("-3 3 I 08..07 3 a 13.0 0O 310..07 Mo Mlalo ry ( n -- 13J 330..03 10.7 0.0 00 S.3 00 faa lo ry O nly t"-0 3 | 50 44.3 00 10.3 sa A Q-m S O r f C(ur-0rM.a0nI* 3.0 30 3 0.3 17 0 74.1 3a Ho H tlo rf t--e.aIn 18) 03 10 0 00 0.3 11.8 0O *AA o x t c u n i a i i o l If)* I f * a cT A o n civ c a l a g o n a a . b o m k1 t fi* to ta l g ro u p a n d tar m a tw o a p a g ro u g a . --w a found to b a n o t H o n o u r * b y ] ' la a l ta r r a M < A a r e a n Conflngancy laM aa. f 0 1 < ! * < . 0 5 tar H i l a r y onry. y o u n g r c*d b y I ' l a a l tar in d a p a n d a n c a in c o n t n g a n c y latAaa. t 0 1 < P < . 10 tar C iaiarA , y o u n g v o t a by j * l a a l tar n p a p a n d a n e a n u y in n g a n c y ta Ma a is related to age in the three chlorarne groups, the number of persons in the age group younger than 50 years was too small to achieve statis tical significance. There .was no asso ciation between the history of upper GI tract ulcer and chlor&cne status [Table 3). While the number of subjects reporting a_ history of cancer (other than skin) was small, ail of them were found in the group aged 50 years or older, and the percentage in the exposed group was not, glgntfteantly dillerent from that in the not exposed group [Table 1). The three bladder cancers were reported by persons t.tposed to p-sminobiphenyl, a rubber additive that was also made in the plant. Physics! Exsmfnatfon Results There seemed to be no difference in blood pressure findings between the exposed and not exposed group. The criteria for determining normal for combined systolic/diutolic values were leas than 1-40/90 nun Hg for subjects aged 59 years or younger and than 160/95 mm Hg for subjects i-K'*! 60 years or older. For diastolic alnnc, less' than 80 mm Hg was con sidered normal. Diastolic values of 80 to 89 mra Hg for ages 69 years and younger and 80 to 94 ram Hg for ages 60 years and older were considered borderline. Diastolic values of 90 mm Hg or greater for ages 59 years and younger and diastolic values of 95 mm Hg or greater for ages 60 years and older were considered high. The significant- clinical examina tion findings as related to exposure status and age are found in Table 4. Of those who were clearly exposed. 4AMA, KUy II, 1DS4-- Vo! 251. No. IQ ': T a b la 4. -- s ig n ific a n t O t a cal F in d in g s y E x p o a u r a S t a t u s a n d b y A g * Hot A ga < M yi, \ Ago y r , \ FW adtag O tan o v * Acna O gw taftl EnoaaJ, X (n-- 2C3) 53.7 3.0 (w xjaad, X [n -- 1631 0.0 11.7 E io o a a d ln -S tl 45.1 7.8 Not E * o *a 4 (n -- lOQ] 0.0 10 O E tp a a a l (n-- 133) 58.3 0.0 Hot E lp o a ta (n-& 3 ) 0.0 i.e Actinie a lla i gala * f S Baaal oat ao*natana| f T t f i g M ' a Ou m j * 1 ' farau a w n 50 1 0.0 di> 8.4 30.1 4 .3 0.0 t.B 37.3 3.0 0.0 3.0 10 0 68 4 40.2 0.0 8.0 l t . l 0.0 C D 0 0 1.0 5.0 3.2 P F -e .O O O l: Vataa ta* L U i r A H a a n a a a i c o m p a n a o n trf a i p o a a d v not a a p o a a d a o r o a a a g a m a l a . P rf . O d < F < . t O ; v ataa tar U a n t a l H a a n a c a t c o m p a n a o n c4 a a p o a a d not a a p o a a d a c r o a a a g a a IT la . 1 .0 0 0 1< / * < . 0 t : h a apoaad. y u g y ota. by Fiabar' a act laal. P| . 0 0 t < / * < . 0 t : In not a a p o a a d . y o i r g v o t a , b y Faabar'a i u d la a l. I.O O O K K .m i: v a lira tar U a M a f - t U a n a t i l c o m p a n a o n o f a a p o a a d y not aapoaad acroaa aga l. O O O t - i/ ^ . O O t ; h aapoaad. youmg ro ta, by R ah ar'a aaact laal. * F < . 0 0 0 1 ; In not i o o < y o u v g v o t a , b y R a b a r 'a am a M , 52.7% still had chloracne, 62.6% were mild cases, 33.9% were regarded as moderate, and 3.8% were severe. The diagnoses of chloracne and acne vulgaris were made by qualified dermatologists. The criteria for diag nosis of chloracne include the initial appearance of comedones, milia, or epidermal cysts on the malar, temple, and periorbital areas that may subse quently involve other areas of the face, the-neck, forearms and arms, and scalp and genitalia. The scrotum and penis are commonly affected m persons whose clothing becomes heavily contaminated by the acnegenic material. Lesions may become sec ondarily infected, especially on the trunk, forearms, and genitalia. By contrast, acne vulgaris that usually starts in adolescence is seen as inflamed papules, pustules, and come dones, on the perinasal area, cheeks, chin, neck, and back. It rarely, if ever, starts on the malar or periorbital areas. The akin of the affected sites in acne vulgaris is usually very oily or greasy. In the case of chloracne, the skin surface is usually dry. Persons with acne vulgaris, exposed to chloracnegens, may experience the devel opment of chloracne. The lesions of acne vulgaris may increase in severity and lesions may develop in sites not usually or previously affected by acne vulgaris. Among the exposed, 59.1% were found to have actinic elastosia in contrast to 30.1% among the not exposed. There was a significant dif ference in the occurrence of actinic elastoais between the exposed and not exposed in both age groups even though age a a factor in this clinical finding. Three cases of Peyronie's disease were observed among the 204 exposed. All of them had chloracne at some time and they were all older than 50 years. Peyronie's disease is characterized by induration and scar ring of the corpus cavernosum of the penis, producing distortion on crec- 2.4.5-T--SuiKind A H*rtib*<g 2375 I iI ( Tabu 3. -- Significant Clinical Firming* ir CMoraCna Slalua in pOlfrd Only and by Aga f w *~* Acnm tam e 11 S a u l c *4 --orTT->ko-- !>i m Malory Onfy, % t.S 47.1 3.0 a.o 0.0 C w tw ii, X (n-IOT) 0.0 74.0 8.4 0.0 10.3 Ho HMaqr, X tn -iai 10.7 so.a 3.0 0.0 0 .0 A p--<30 |t , X M alo ry Or*y 0.3 31.3 S.3 0.0 0.0 Cm n t (-331 0.0 30.3 0.0 0.0 0.7 Ha H U lory ( -1 2 1 33.0 0.3 00 0.0 0.0 Ao-a SO y r. X HU lo ry (W r (-031 0.0 si.a 30 3.0 00 Ommt [ - ) 0.0 79.0 10.7 1.3 IQ 7 Ho N ta to ry (n-101 0.0 43,0 S3 0.0 O0 a tli- m ic **,01 < A < , 0 3 ; tar O m n i 4lf1*rAO4 b a r - n n f iu ITv m c n ta r a c n * C a tv g o r U a h\ 5 - 40 y u n o r y o u t a - r . b y y 1 i M l tor ta d -tu r n U n c Iry e o n u r Q a n e r U b t* . r.OOOl < / * < , !; k r o w a l b -t -- -- 1 m * rhra c M o r a c n a c a lv g c v to a ki a a CO r " ra or ota -r. try y * l a r i tar V x tap aaxtaro a bn c o r w ^ c y la b ta a . |.0 0 < /l< , 10; in ta on on ahUr riocryWoofn ctafnt aa.Kynr *ar,>0y * o vO<d . rboy*rd.> W by f n Wa u ci t atuacf.l taal. TaN 8 .-- Exposure v Flaaxna Ljpds < 1 C talllH lI Uotaa TrWyWtaa Lff---Oanvty knprol--l (ioUalaroi g y p o a il n X-SC 300 311.13 a 3.33 300 I49.SS 7.44 190 130.74 2.40 700 40.03 0.01 % Out of fliny** 7.3 14J 7.7 9.S Hof ti>Qi 0 ft 2 r S t 03 704 07 3.97 10S 130 S3 7.73 139 127.00 3.00 103 *4.23*0.77 X Owl of Haag* 10 4 19.0 0.3 10.4 NS NS NS NS " f lt iv a n c a n n j a i tar 0Laam a c t a l a t i a t a , tn ^ y e a rx ta , a n d t a - danabfy C o o p ta a n c n o U a la rc f M < a d a h rw ) aa btaa m a n th a Q a p a o ftc QOiti p a rc o n n ta a a J a la n n n a i by m N atio n al | . p 4 R a a a a ta i Pt0r*C1. R a la ra n c a f i t a a a tar b ^ rt-d a n a rty tpoorotaan a w a r t w d a n o eA n ed a a a b o v a irta >qa-<n o t a la a m p a k a n lN aa d a ia n a n a d by Iba H ao o n al L o d fV c y a c l. Lion. As noted in Table 4, there was no association of findings of basal cell epithelioma and hirsutism with expo sure. The sample size was sufficient to detect a threefold increase in basal cell epithelioma and a fourfold in crease in hirsutism for exposed over what was observed in the not exposed. Table 5 identifies the clinical find ings in the exposed population in relation to chloracne status. In these groups, actinic elastosis was found preponderantly in the subjects with persistent chloracne (74.8%), but it also occurred significantly in those with a history of chloracne only (47.1%). Of the exposed with persist ent acne, 10.3% were found to have malar hirsutism: nine of these 1 1 cases occurred in the group older than 50 years. Actinic elastosis is a problem found in persons of light coloration exposed over many years to sunlight (eg, far mers' akin and sailors' skin). It is characterized by swelling and frag mentation of the elastic tissue ele ments of the dermis. There was an association of actinic elastosis with chloracne. It seems that the percent age of persons with severe actinic elastosis was related to presence of chloracne and that it is more severe when found with chloracne. P lasm a Lipids acne or those who never had chlor acne (Table 7). There was a greater Plasma cholesterol, triglyceride, number of persons with high LDL LDL cholesterol and HDL cholesterol cholesterol levels among those who were classified by age-specific percen had a history only of chloracne than tiles as determined by the National those who had chloracne currently or Lipid Research Project data.u Plasma never. The mean lipid levels for these cholesterol, triglyceride, and LDL three chloracne groups were also cholesterol ralaes were classified as compared (Table 7), and no signifi out of range if they, fell above the 90th cant differences were found. percentile; HDL 'cholesterol values After adjusting for age, height/ were classified as out of range if they weight, smoking status, and alcohol fell below the tenth percentile. The status, no significant differences were frequency of out-of-range lipid find found between the two exposure ings was compared for exposed and groups with respect to mean lipid not exposed groups (Table 6). No values. The interaction of smoking significant differences were noted. status and alcohol status was also The sample size was sufficient to added to the model, and no differ detect a twofold increase in the fre ences were found between the two quency o f . out-of-range cholesterol, exposure groups. triglyceride, LDL cholesterol, or HDL To detect differences between the cholesterol values for exposed over chloracne groups with respect to what was observed in the not exposed. mean lipid values, the same adjust After adjusting for smoking status, ments described previously were per no significant differences were found. formed. No significant differences The mean lipid values were also com- were found. pared for the exposed and not exposed Log linear models were used to groups (Table 6), and no significant detect associations between frequen differences were found. cy of out-of-range lipid values and When the lipid levels of the exposed chloracne status in the exposed group group only were examined in relation only, adjusting for smoking status. to chloracne status, there was a sig Findings are aa follows: (1) Out-of nificantly greater number of subjects range cholesterol or triglyceride val with low HDL cholesterol levels in ues were not associated with chlor those with persistent chloracne than acne status. (2) Out-of-range HDL in those with a history only of chlor cholesterol values were associated 2378 JAMA. May I I . 1084-- Vol 251. No. 18 2.4,6-T---Suakiftd A HartibafQ v- * i c%0--*Jaro4 Trte'r0*'*** Tab!* 7 .-- CMwacn* Slalui inExposed Only v P la a m * Ue-dm Matocy O nty A X *se at 2 IS . 16 X *.07 Q7 la a .o o x i4.ee V, O ut o/ Rang** 11.0 r.s C u rran f A lit too 2 10 .33 x3 .1 7 106 163.04 x 0.39 % Ovl of S * tg ' 4.6 IS.1 Ho HHfcarr % Ouf A I x M .' 36 304.86 X 7.13 of Rang*.* . : 7.1 TO 149.11 X I6-3S I4.S CftCtatlvroff kxiprof**! M 1 4 7 .6 4 x4 60 67 45.64 X 1.17 13.3 3.0 103 134 4* x 3.66 106 4 4 .8 3 * 1.31 2.8 14.3 27 130.86 x 7.06 26 47.76X3.31 7.4 7.1 'f U i w H i c * n n ^ n lo r p i n m t ( J MI i l i f e l , t V y o n ] , a n d l a i j w i m y ^ a x r g l a n t f i e i i i n < m t * d i u r n i W u I h t n Oh M l w m d b f IH* K a n o n a i U > d H n m L f t P r o r a t i. B a le n a n e * r i n g * * tar h ig ft-d e n a *y l o w w a n lTO Ji l mx * r m f c n d a a a t i ( a S M a n M H d b r trt* H a t o n a i Llo< I B a a a a r t i) P ro ra ti. ed P < . 0 1 B : ter c w p p a t o g fre gu a n cy O U l-O f-n n g a la va la in I t o ffa a a t f l o n c r a CFTXJO* edI P i . O f l ; ter o o n p a r t n g tr a g g a n e ? o u l-o f-f o n g * la v ala In m a g ir a * c N p r i c r a gro uoa. DOti p M v N * a p i eia u ftc I m n p e r o a n f* a a a with chloracne status (.01 <.P<.05), two exposure groups after adjusting and the decree of association did not for the effect of smoking (Table 9). No vary significantly by smoking status. difference was found between the two (3) Out-of-range LDL cholesterol val exposure groups with respect to ues were associated with chloracne FEFu.n percent predicted. Percent- status (.01 <><.05), and the degree predicted values for FEV./FVC and of association did not differ signifi FVC were significantly lower in the cantly by smoking status. exposed group. Furthermore, there Pulmonary Function Exam ination was a significant interaction between smoking status and exposure with Both forced expiratory volume in respect to FEV, percent-predicted 1 s (FEV,) and forced vital capacity values. When adjusted group means (FVC) were considered abnormal if for each smoking status exposure the observed value was less than 80% combination (Table 9) were examined of the predicted value of Morris. A to determine the nature of the rela * FEV,/FVC percentage less than 70% tionship, no significant differences was considered to be abnormal. The were found between exposed and not forced miderpiratory flow rate exposed workers who never smoked or (FEF,,.,,) was considered abnormal if who formerly smoked. Among current the observed value was less than 70% smokers, however, there was a signif of the predicted value of Morris. icant difference between exposed and Consistent differences in* abnormal not exposed workers-with respect to pulmonary - function values (FEV,, * FEV, percent-predicted values. FVC, FEV,/FVC, 'and FEF,,.,,) were found when the exposed and not Clinical Laboratory Findings exposed groups were compared (Table With regard to clinical laboratory 8). Among current smokers, there was determinations other than plasma a significant difference in frequency lipids, no significant differences were of abnormal pulmonary function val detected between exposed and .not ues between-the exposed and not exposed groups. There have been, exposed groups, but there were no reports of abnormal levels of alkaline differences among persona who have phosphatase, SCOT, SGPT, and formerly smoked or among persons GGTP in other populations exposed to who have never smoked (Table 8). TCDD for short or long periods; how Logistic regression was performed ever, no differences were found in to* evaluate. the.relationship between these cohorts ten to 30 years after the frequency of abnormal pulmonary last date of exposure. ! function values and exposure after adjusting for pack yean smoked. Odds ratios are given for these ECQ and Rontgnogrjphtc Findings parameters in Table 8. Exposure sig No differences were observed in the nificantly increased the odds for ECG findings when the exposed and abnormal pulmonary function values not exposed groups were compared. even after adjustment for pack years When the cheat x-ray film findings in smoked. the exposed group were compared The means of the percent-predicted with those'in the not exposed group- value* were compared between the and separated by age, the arterioscle rotic changes and pleural thickening differences between the groups seemed to be age related, not expo sure related. N eurological Findings and Nerve C onduction Velocity M eaaurem ente When exposed and not exposed groups were compared for frequency of abnormal findings on neurological examination, no differences were found. Nerve conduction velocity measure ments require controlled atmospheric conditions and uniform conditions of testing. Ambient and body tempera tures were recorded. With the tech nology employed, it was at best a screening procedure. All subjects reporting diabetes or reporting a high weekly alcohol intake (^ 3 5 ox. of alcohol per week) were eliminated from the data analy sis. After these deletions, there were 278 with complete sural and 294 with complete peroneal examinations re maining. The data from the nerve conduction velocity studies were cor rected for body temperature accord ing to the deJesua" method. The ageadjusted values are presented in Table 10. No significant differences were found when the two exposure groups were compared or when the three chloracne groups were com pared. -- R eproductive E ffect* Information on reproductive fac tors and birth defect* was elicited from the male participant*. Neither physician nor hospital records were available to confirm the information. A comparison between the exposed and not exposed groups for pregnan cies, live births, infant deaths, mis- J * W A M a y 11. 1 0 0 4 -- V o i 2 5 1 . M o. 18 2 . 4 . 5 - T -- S u s lu n d * H r t r b * / g 2 3 7 7 Tab*a 0,-- Exposure) &oup Maaruj ofPare/I-Predictad Pulmonary Function Parsmafera Adjuslad lorSrrjoking Slatua Function F E V .- FYC* F ^V ./F V C % S*o k *i StM tua Form */ Total a*. C ltW H d X se 107. 12 r 3.03 1 0 1 .0 2.03 . e a r 2.25 00.30 r 1.-0 0 3 .7 3 r 1.17 7 a .a a ro .B 3 ioi.oora.C 3 Hot Eipowd X xst 103.03 X 3.03 U M .oax2.ts 102.33 X 2.03 io a .4 2 x 1.57 07.00 X u s 7 0 .0 3 X 0 .0 0 100.10 X 4.30 F MS MS 0.0003 0.0104 aooea 0.0003 MS r t i c i i M *onr*d u p n r o r y w o k In 1 : F V C . lo r c a d vital e a p a c * / ; V > * rata. foroad ir U u p r > n r 7 T a ti 10.-- M a a n H nr C o n c o c tio n V e lo c ity * fo r ttva E x p o tu ro G ro u p a n d lo r Ova C N o ra c n a Svrt>Oroupa| . C ateg o ry tJ p o a a d l xxseoo Met E c p o ir i S x S C CrO C M w v ii , hiOoqi o V yf X X SC (n) O t e w a . o in > 4 X xS C in ) O *9r*oria. nm .c X x SC (n) U ^ar - 00.00 X 2.33 (0) 01.01 X1JS3 (01 03.03X0.03 (3) 0 7 .ft3 x -C .il (B) 5 3 .1 0 x0 .0 0 (1) H *rra Tw ted lin m ia l 4 i.7 7 z o .4 7 (too) 8-rarf 42.03 X 0.40 (tfiO ) 4 3 .szxo .0 3 (134) 4 1.4 0x0 .3 4 (12fi) 40.00 x 0.77 (00) 4 1 .1 4 x 0 .0 0 (51) 41.30 0 .0 0 (B3) 41.S7xQ.70 (74) 40.81 t 1.12 (24) *' 4 1 .2 3 X 1 .3 0 (26) tor a g * . f P > 9 J4 l4 riot a^gnrflca/H tor oom p artoon e t a rp o t a d w m not a& p oaad wkft r a t p a d to l i n * / , p a ro o a a l, an d M a t , and atao tor o om p artaon o# Via thraa d a o r a o n a c a ia g o rta a vrtm r a a p a d to t i n / , p a w i l , and a tr a l. carriages, birth defects, and adllbirthfl is listed in Table 11. There Ottvar W o rk Expo aura a of the Study Population were no significant differences in \ Other than 2,4,5-T and its interme these parameters between the ex diates and/or contaminants, all of the posed and not exposed cohort. No workers in the study were exposed to data were available on age of wive of multiple chemicals and industrial workers. processes under varying working eon- ditions, at the same plant and/or other plants, between the late 1930s and 1979. Rubber processing chemicals iden tified by the subjects as other expo sures Included diphenylguanidine, the beoxothiaxolesiilfeoaimdes, deriva tives of m-cresoi, p-phenylenediamine derivatives, and 4,i-dithiodimorpho line. Additional chemicals named were ethyl parathion and methyl parathlon, phthaiie anhydride, a- and p-dichlorobenxene, a- and p-nitrophenol, toluene and mercaptobenxothiaxole derivatives of tetram ethyl thiu- ramdisuLfide, and trimethylquinoline components. Seventy-nine subjects, or 21.5% of the 367, reported in-plant exposure to p-aminobiphenyl, a known bladder carcinogen, during the course of their employment. These subjects are peri odically examined in a clinical sur veillance program established by the medical department of the company. Subjects reported the exposure and the monitoring program during the interview and to the examining p h y si cian. The data relating this exposure to 2,4,S-T are described in Table 12. COMMENT In any interpretation of the medi cal significance of data elicited from this study, it is essential to consider the characteristics of the cohorts as well as the strengths and weaknesses of the design of the study. With all industrial populations at risk' in the 2 3 7 a JAMA, M a y I I , 100--- V o l 2S 1 M o. 18 2 ,4 .5 -T -- S uaW nd & H *n z b *rQ 1'*t *\ I1 * l k t * . rv& Ep otm tm cV rm o t to o l,1*1 cr. rr* M o a u l n o a -ml ' * ^ 7 <*. arar*J 6 . <1* l* rr Vx AjcV* ctu* b d *. c o n g r u i . v j i k I m ot t *. po*r c y <o a*eta w t i y tra O . elkjo a tu ripa c* Anparm. o a * > a i i a w x i h a n ci hto*. cy - o c h y w w n . D e y n 'a ayrOnOTH, astd h w n t . |T>a a f l n x M in f u i O w ( I S O a 2 0 4 tor e * p o * d a n d I U * l U l t f n o i a j p o a a d ) -- TM d u a to M n ilo - r' C fi*e or i m i * j dbd no* r co n il <ro (Wn r c o ri n k* in a no ~ -f " T - -- . O V a in ava a p o i ifl. T a t A a 12." Hitoory ot E x p o w x w t o p^Am lnot)ipr*arTy< ( p A b ) a n d (2.4,5-Tricf*ioropttorioxy)actte A d d (2,4,6-T) y14to ry ot BUw N e o p l a s m s H * t_> 1.1n r to D O W * I.4 .3 -T Z.4.S-T PAA oc p A * Cj.Tiii -- g'a t o iiw B U oO -r h^rorf Ca-oa-r w w t No. % No. % * No. " a 0 0.0 0 0.0 1 I2.S o no 0 0.0 . r " ; *M io ry u d iton i iad i u n k n a rtta a an d r a p a i to am a n in g t O p y r* rm A ia> f aicfcjto a. Vaa --a 2 .4 .4 -T D l,**O T . No.* % r 9 .o . r - - n : United States, particularly for long may have been exposed to 2.-CS-T, the term follow-up, randomization and rrmfummint TCDD, and other chemi participation requirements for pris cals varied markedly, Spbiecta re^ tine epidemiological protocols are ported exposure to the 2,4^>-T process rarely satisfied. In this study it was for as little as one month to as long as not possible to match the exposed and 20 years, and exposure was often not exposed groups demognphicaliy intermittent over a period of years. It on basis of age, employment status, was difficult to accurately designate and education level. Although the two the duration of exposure for many of groups were defined on the haais of these persona. The data do not pro definite exposure to 2 , < 5 - process* vide characterization of incidence or and ijg^^videncg ot exposure to 2.Cb-T ~ dose-response relationship. anywnere in the plant, no iniorm- ~ Data obtained from interviews and tion w*a available about levela oT'> clinical examination-! -conducted by .&-TCDL) in the work environ different physicians have inherent ment or_ in the trichlorophenol that biases. Nevertheless, the available was procured o: la the Anal product,' populations provide useful informa 1 hince was used ubiqui- tion on the prevalence of biologic tou5Iy-la a weed killer In many gar effects in the population exposed, aa dens and firm s, the possibility of compared with those who were not exposure to some TCDD between 1948 exposed to the 2,4^5-T production. and 1969 exists for both groups. There A comparison of manifestation of la current analytical Information effects to TCDD toxicity In humans demonstrating that dioxins including as observed in this population with 2,3,7,8-TCDD may also be present in those observations made in experi the community environment in fly mental animals moat also consider ash and, flue gases" "" from incinera the acute, subacute, and chron tion of domestic garbage and indus ic effects in humans already re trial chemical wastes.**"*4 ported.14^ The degree to which each subject The subacute effects of TCDD tox ic! Ly in the group of exposed persona as described in the reports cited in the references were characterized by cutaneous, hepatic, aad peripheral nerve damage. In other populations, where hepatic changes were observed aa a clinical subacute effect, elevated levels of SCOT. SCPT. and CCTP were reported.1,0* Doses of 1.0 kg/day in rats will induce altered liver function, elevation of alkaline phosphatase, lymphoid depletion' of the thymus, and increased excretion of urinary porphyrins and d-amino~levulinic adcL* The effects on the thymus have not been noted in humans, although there have been some reports of elevation of alkaline phosphatase and dALA levels in long term exposure." Elevation of alkaline phosphatase levels was not observed in those who were examined in 1949, 1950, or 1953' or in this study popula tion ten to 30 years after exposure. . Tetraehlorodibenzo-p-dioxio was fouod to induce cancer of the liver, lung, palate, and nasal turbinates in rata." An excess of cancer of all sites was not observed in the mortality analysis of the group exposed to the runaway reaction materials,1* nor was an increased prevalence of cancer of all sites observed in this study popu lation. Cancer of the liver was not observed in this study population, nor was an excess of cirrhosis noted. High doses of TCDD (30 ppm), administered orally or subcutaneous ly, in pregnant mice* and rats may increase the incidence of cleft palate in mice and cystic kidney in rats." No teratogenic effects were observed in rabbits receiving 10 to 40 mg/kg of 2,4^5-T containing 0.5 ppm of TCDD or in rats receiving l to 24 mg/kg of 2,4,5-T with the same TCDD content." It has been demonstrated that hyper plasia and ulceration of the gastric mucosa occur in monkeys after lethal doses are administered." In thU study population, a statistically significant increase in the history of upper GI tract ulcer was found when the exposed were compared with the not exposed. Birth defects as reported by partic ipants in this study showed no differ ences statistically between the ex posed and not exposed groups. In rhesus monkeys receiving 500 parts per trillion of TCDD, early abortions and inability to conceive were obMrved."14* The* affects have not been * ' U u A W a y I I , 1 0 8 - 4 -- Vot 2 6 1 . N o . 18 2 .4 .6 -T -- S u tld n d 4 tW U D rg 2 3 7 0 obwrved in this study population. This study indicates that the pilosebaceous effects of exposure to the 2.4.5-T process were persistent in S3% of those exposed. The effects of the CClRpRoxaiarocriro.hrovriflU*rii*anDli.Wd,W.PWaIU.hdrDrDaHaey;.nanmC;B*lNbaECrnitiohcchaBkEr.al.uoJrDStrnt.uaoaalUoiko,DOi;nU.idAbD:C,o.hmHPaa.aar/l,SmdamaDRiWtL>ahml;,inaHMniLiaOrFr,.;, kind of care received by the various R ifacioca) subjects may be a factor in. persist ence. Since biopsies of the site required to identify and measure TCDD were not available, the pres ence of TCDD or its metabolites as a factor in persistence could not bo ascertained. There was an association lVU1h9i<n5Iri0.g.UiAnJoinulaboli.ytauyinn1w9loRo5f,0r.pSCCouibranttkciaiiionnidonf (aJAtRiaC.Rgo:OamCtctptrboarlinboHyerr,pa aNaitrco.u nWroitf LIMabSo,raAtoprryil, itcfaXZcty*crGKlvioiicr*lndaamtrtnb*ia*aajorcJnk.aaaSPfeJlaxh; uncElux1rl9tKmr5aH7no;:4fa4Cl:*yh3o3J-o7nc.r-r3iin3l**3ard.laaedchhalolroroarmaecnaoatt. of actinic elastoais with the occur rence and persistence of chloracne. This can be interpreted as increased susceptibility to UV radiation dsra- e. There was an association of history of upper GI tract ulcer with exposure. It was not possible to' ascertain a designation of ulcer by site without GI roentgenography or endoscopic information. Among the exposed crBlScmLDdAoehohhurdar756aAlcaiearoioa.i.J.ncMamrtrotlImOCo.JBimfnfQnatiadAnrrlrlaiamcromdiiiattinbb.riwrarlbcdaiuiMuelorr1pftyAhlKohru9aOoio*olo7rcDdRLaroon4ta-pc,cU.rnn;11Jqho4uKtCr,t.9:ou9ppy4avo7hr:iAb-rfWITtir/5ldihrao4ofaov1ooi*and5wrrofpSraai-etrilp1cekOcpelir1h5on1nyano9-e79dtra5n7rca.rJa7iap--X5fbona.U3iclh7iaa:oKar7yp:.cal1iion1orartnd2ioa:iBbbpie2au-blma1or9oa.apioco87.rarikAdaf,-idctt2totkoapriaoK9ocXi.tad8nri.nAArym.XatattlrDn7paiRwbd,arX,a6aomodtm-nrdtilokAt*xCnutaminhccutri-asooartd-sit-rj./ group, ten subjects reported surgical treatment of the ulcer, while none of the not exposed group reported surgi cal treatment of ulcer. These data are suggestive of association with expo sure; no definite conclusion can be drawn because of the qualified nature of the data. The association of upper GI tract ulcer with exposure warrants additional study with an appropriate ly designed protocol. Mdaitppth1PnaLiohlea9tr-a9oIXIcatyoarXdnh.Irl-.rTl.itoediio1UhAPaA9oliSGa9ooro:Wrcim7e7rPgluirofhanA5Xdiipitfiwncn1ttGtrtnahday-ilEaat7:an?lCpwu;9yaCiAm6trWon7p-Bai-JhoaP.faHT2Ncrlfr,tSaocAhi1.alccmawr3a9Slr.tah!oLbad7VmoclNHr3oaortn'ooo^iku,rortaatf:adaahra1antrrihf21obaaaiJarAa5DGXdroalti-yaiam.J1n7o.1dipU4on,9Mr8a0l-UyaT.h-a.dtemaI2o1oa-Sihrtd.b;ottm4opZcaairr-loaharcaoDnarrlrof3*laiofiCandIociirJae.a.lc-hAnorZceuBd-rrf,pnud7olriaidC2.davro.JAaaiLtrJbLippmi..n5*nnorao-aoraATLJr>---I. Among those whose chloracne per sisted, there was a higher frequency Z*XIv7tir-pVlnaob*H-aJrcCaMl,lXoNro/o'tlrolrbnrapoJexAdp.-1pZ9-7do1ilo5dr:i8BJ7G-9:9(.TTCoDriDdt)y ionf of low HDL cholesterol values. Among those with only a history of chlor&cne, there was a higher fre quency of high LDL cholesterol levels. There were no differences found between the two exposure group* with regard to plasma lipid and lipo protein values. There was an association of altered pulmonary function values, espeaally EEV--in Lhose who were exposed and d2CI[21na90iJSaoi:L5I172oX.d172Hwno91i--JC/tloShi(*o4nodwuLediqXr*aaatueronLGiohaao5*l:dy)o.-ACrCoblTrahdyD^clirhab,rcll2arioUocnJtcoraLzoohi.oo7pc-AJrJmh^a5-ap-ldJnPtef*AMaaiairi;rlXyXPaTcahotahaocla.rldaoary1Tmlr9cookc7ldxaf3oriae:lvbc1dhdxya1adfm6*1:AUo19tatu0p-7nwd1p1dt--;f *TdP1i6akolI7rafdai6ir.lomo&SEamlSoaaa1dnoi7tbllCh-d6a1Pt29y-XT71R1Aio;,m,SffiJSccC3a2cr9.Jyhta,wT7a-or3ntrD-t.lUoGcHt,JraABeA.MapyNpoeiirrtoaPdJcAEiibal.aarnraartaoEe-aDaol-'l who currently smoke. This suggests flraulta of a two-yaar chronic to rid ty and otvoo- the influence of the number of pack years smoked as well as arposure. ... There was no evidence in this study . that exposure to the Z.C5-T process is associated with an increased preva lence of cardiovascular disease, he patic disease, renal damage, CNS or peripheral oerre problems, reproduc tive problems, or birth defects. 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VSurrlpjraurr rOAlLPiifoaooir2no/edryn2ouj..<omAaprAZiTHAeoolaXotfu/ciaerikrwndwUfJu,llaoaAai9OiradIafk.rclldilOaiSctAcorrDhZiuiblC2aoAabmrIrrMmworpIoioMcoAhH-aRaCaItd.RalVdiop--:alpli-To*ooph1A-rUa-Co3pclo7munrw.ua/oanc-arOnhataall,molcoirccCavoiydhdSaij'caobriaapta*r.wnaaoJd---. fpoaoPS1BtWLnpUHD1Di1IV-im9dpto9mofiraaaohuiaZ27273322Z7tardoorunJiclup915r7401d9wiX/1XcldfIriS..l.Pi/..aRNhrUtaCmaS.odhEoliPbGmC(HdoCFKrFT-ioraUfHi.fZ1pPual.fYIrcXroRaaIiar92Sla1pJi/u2t1it/CoiaUe7vtn|SphaiMib9imo0wutIiA7dhr.t:--ho7o--ou.oobw1ra.ur)SRDLi9rabo.iaafoTtrW(1avp-i.klFAp"aalenr^lvaIh1vhprlfL*ndJom7Ld^ixljtUI-h7.aTTFlaRut|9jfu2dJLk-ria'Sai.AL,U-<Xa.EIdTairro1t,LlanCilpiSNLDNd,aXrI1k5aTD.ia<a*QSTuu.l7Ao--oPraot.a1oGHIic7kTnf5ArCfatcti1w/Uhxat.aXa.o.H4tnutAro.niUO.o,a*dmnYulia.utaoXnraboNialilAt1uNalfotCAalUpAaallu.njn7ray..XiBCnu,ucakp*uJdD1Tri>poa1miAD,1.paJoltG1unl9oiMroafyJAd:.ASuibam7dnfourpaCSia:UA0nt/ruAphSoacu--o-h.AiWdo4LtSaniaitivAiupf9Xnlewi.LSoluPr7pjo/ai:WoaXlyBi/ll-ofdn,oUyofii1coa7aPCAriatta,ari4P5rtnraeuo'lrtUrr5rruBW-epuooroidap/Nr9ram.7crpftatdaan-w9uw'SupctJaa/iv.AroAaauauataunwCCoalr.mbfdLA^tRw--SvDivoin1lliobvLfioooaod-Haaclro9Aoa--wAt--narttoaArnlAremJ7oaocaain*caatTaIf-tf-,-i-.....-.., NdrRrmpotitrbA33ipaanaX2rranon.cirLrmlatfJHiinocf1trpoPoum9pSorot8CaJanl11mnrcGa9KrJorepi70iotrdaa31lrdoaAJnS9oLOnr*S-An2b*.i1Fla1O/LaotSE\0oralpidaMndaircurr1riKtyW8Hf.i9tAvUiaLa.crldufitoCuaanarpttaoaauponrrCrdrbo-yaidaaoiicaa,oChowlo'.dEoErnnCr^ana/mLrrEiirrraCa--oovnonaDid-r--2elCtmTir6UaninJ-mooo7LifIXi37r3cton-nLo.757aiaho.rct.f.1Jr.afliaoB99iorGnWEMm1ifn6ae-flaSrXoUonAbaoorSd3raiyaOpXjiaka9bnaaSpdv-:1*G1ratiir3atUna2rb:hP-itoSaRiLAwaaTAlU-moJ,1aEae,nrDU-3orn,WokomSdyKdcnorU.wakoacmobrcrapralaroarnoarirloaannnatatinlaaimraanxoi1tlofi-a79olaPlnrfiJo7,ant-bbAVi6drtdaEtd.X.it:aiahrtuazP1xNaPyaUaop5iroCalaeo5dp-aroA3aaEiikLt(a-dooru:Tn6ianrddiC7CvcOmllpyioa1.iDNtrrrd.ir'BoiaooD,lffa*Arndiia)ln.Jm:ialb*rtiaDJuaRttnbtranotmoiaAtaln-f-,'. dio3r3i.n-Caxopuonsrdy wEoDr.kaCrai.yLloorooDaWi 1, 7|7(o9;*L4a46U-5D47. .al eblaDC4aaEa11iLLh17ttXroomodpa034744lroJoria.m30Hi320o7TyaaoLir....;1ritaoo1Ma--ooAcU6AroErdTcr3p-ra3*nfoiTmlclTdtobhtliinN9naoCe2ic^oa6a.toooflJor4nollraaraoroLi-Jiaiai/Jooacafntf,aElrR7i6o7aai[irdie.nciSdor.,^mia*Fi.oJ1-iJWVmBlcLo9rr5*lTirraoTao,0aP7iirranad1i0wlTir;actuiautoChipof*Uh-roadCTooJypioaotiii3rdomralialtlrF6oolraaoap1tr-DliromMbfUarca3oaoAia7otZdKJftcia7o.nTyPnJr.JabfXaLaoV:&aanDatxL7oda2nH1diJnacf.ba0mL,Saaa-o-&ynlr6calSiU-2airi-i^b-a1tilI1JUT4rrcrh9bi0,Riar.iol77ii9boar7ltL7in.iorSomr*,Jani1-rc.oaJnlop*5FPira1nptlH4o9oita.iib0Rcrdc7nnoaa1aa*3laJl*dd4-----;l, 2 3 S O J A M A . M a y 1 1 . I & & 4 -- V o l 2 6 1 . HO. IB 3 ,4 .6 -T -- 9 t**h Jo d A Hw rrrb-acg r.* . M o n san to Monsanto Company 800 N, ndbergh Boulevard St. Louis. Missouri 63167 Phone: (314) 694-1000 LAW DEPARTMENT March 16, 1990 Ms. Carol Van Strum 7493 E. Five Rivers Road Tidewater, Oregon 97390 Re: Mortality Studies of Nitro Plant Population Dear Ms. Van Strum: Please find enclosed copies of the two mortality studies referenced during our telephone call today. I have also enclosed for your review, copies of the trial record regarding Dr. Roush and Dr. Suskind which relate to those studies. I have also included in this packet a chart which was prepared during the trial to illustrate for the jury the statistical manipulation which was being undertaken by the plaintiffs' lawyer to artificially create the impression that there was an excess in cancer mortality at the Nitro Plant when as explained by both Dr. Roush and Dr. Suskind; the actual study data would lead to the opposite conclusion. If you have any further questions regarding this litigation or the matters addressed in this correspondence, please feel free to give me a call at (314) 694-2821. Sincerely, DFS/dlr Enclosures CC: Dan Bishop w/o enclosures \ Telephone: CAROL VAN STRUM Science Writer 7493 East Five Rivers Road Tidewater# Oregon 97390 (503) 528--7151 Telefax:_____ (via volcelInc) April 2# 1990 David Snively Law Department Monsanto Company 800 N. Lindbergh Boulevard St. Louis# Missouri 63167 Re: Information request Dear Mr. Snively: Thank you for the materials you sent from the Kemner case record. They are very informat ive# and I appreciate the trouble you took to copy them for me. Would it be possible for you to copy page 2 of the Monsanto Offer of Proof for me? It was missing from the copy of the Offer that I received. I also have a question about one document that puzzles me. The attached copy of Table 9 was stapled into the copy of the 1983 Zack and Gaffey study that you sent me# in front of page 586 (Table 9) of the study. There is no exhibit number on this page; is it part of some other document in the record of the Kemner case? I would be most grateful if you could send me a copy of the document it is from. Thank you again for your courtesy and help. Sincerely# CVS:cvs attachment Carol Van Strum 1' *- -- v W i - V". V % -<uct(. ooi~ ^*vi ^jOii Is a v ^>r>*r r*J C r< tcu ^ acc.*e2, Table 9 Observed and Expected Humber Deaths During 1955-1977 by Cause and ^ r o ,j^ o j l ~ i _ 2,4,5-T Exposure Category Showing Proportional Hortallty Ratios (PMIRB s) ^ u - r> y Q jC e d ^ (Ho L Including Deatha from TCP Incident) Cause of Death All causes of death All malignant neoplasms Buccal cavity and pharynx Digestive organa and peritoneum Stomach Liver All other digestive organa Expoaed Hon -Expos e d Observed1 Expected PHR Observed Expected PHH 58 58.00 100 89 89.00 100 9 10.94 82 a/, 21 17.19 122 0 0.38 0 ^0 0,64 0 0 2.80 0 ^ t? ? s 5.74 52 0 0.52 0 4* 1.06 0 . 0 0.19 0 J ry. 0 0.39 0 0 2.09 0 ' V-/ i L 1 4.29 70 Respiratory ayatem 6 3.78 159 5.58 72 Lung 6 3.57 168*10 4 5.26 76 All other respiratory organa 0 0.21 0 0 0.39 0 Skin 0 0.29 0 0 0.35 0 Genitourinary organa 2 0.96 208 10 2.70 370* Bladder 2 0.22 909 7 0.65 1077* All other genitourinary organa 0 0.74 0 3 2.05 146 Lymphatic and hematopoietic tissue 0 1.35 0 1 2.07 48 Other sites 1.38 72 3 2.12 142 Diseases of the nervous ayatem and aenie organs 0 0.61 0 0 0.83 0 Dlaeasea of the circulatory system 31 26.48 117 .52. 47.37 110 ^Arteriosclerotic heart disease, including CUD 27 19.72 137 43 33.63 128 All other dlaeasea of the circulatory ayatem A 6.76 59 9 15.66 57 Diseases of the respiratory ayatem 2 2.67 75 4 6.49 62 Dlaeasea of the digestive ayatem 1 3.70 27 2 4.06 49 All other diseases ' 3 4.31 70 2 6.70 30 External causes of death 12 9.29 129 8 9.28 86 Hy analysis showed 65 deatha. * P<-05 \ srs. fo . C J c M o n san to LAW DEPARTMENT Monsanto Company 800 N. Lindbergh Boulevard St. Louis. Missouri 63167 Phone- (314) 694-1000 April 11, 1990 Carol Van Strum Science Writer 7493 East Five Rivers Road Tidewater, OR 97390 Re: Information Request Dear Ms. Van Strum: Thank you for your correspondence of April 2, 1990. Please find enclosed a copy of the missing page from Dr- Suskind's offer of proof. The other material which you referenced in your letter was inadvertently included with materials previously forwarded to your office. It is not a portion of a document in the court record of the Kemner case. To bring you current with the status of that case, I note that the Kemner appeal was argued last week by the parties. Monsanto remains confident that the verdict will be reversed when the decision is issued by the Illinois Appellate Court. Sincerely, A:DFS-(K6.ch report health effects he found in Monsanto's workers whan asked by the West Virginia Compensation Commission, and of publishing studies intended to downplay the actual human health affects of dioxin. As a result of the extreme and unfair-limitations placed upon his testimony and this Court's subsequent ban on his further testimony, Dr. Suskind never had the opportunity to respond to these charges, and to demonstrate that his recollection was totally accurate. The importance of Dr. Suskind's testimony to plaintiffs* punitive damage case is illustrated by the manner and length (18 days) of cross-examination of Dr. Suskind after a reasonably concise direct exam (2-1/2 days), and the extensive, use of Dr. Suskind's testimony in the cross examination of Dr. James Webster, Monsanto's chief examining expert. Plaintiffs' counsel spent days cross-examining Dr. James Webster, Monsanto's final medical expert, with the unclarified, and at times unduly and erroneously restricted, testimony of Dr. Suskind, In addition, misinformation offered by plaintiffs* counsel which was corrected and clarified by Dr. Suskind during his direct examination (which clarification was left unchallenged by plaintiffs' counsel despite 18 days of cross examination) relating to the number off workers reported by Dr. Suskind in his 184 health study as having cancer was used, nevertheless, in it's incorrect and unclarifiad state to cross examine Dr. Webster. <Tr. 6/8/87). This Offer of Proof demonstrates that Dr. Suskind*s redirect examination is critical to Monsanto's 2 r M o n san to Monsanto Comoany 800 N. Linooerpn Boutovam SL Lows. Missouri 63167 Pnoo. (31A) 694-1000 May 4, 1987 ENVIRONMENT. SAFETY & HEALTH Marilyn Fingerhut, Ph.D. National Institute for Occupational Safery and Health Robert A." Taft Laboratories 4676 Columbia Parkway Cincinnati, Ohio 45226-1998 Dear Marilyn: I ain enclosing the computer tape you requested in your memo dared April 10, 1967. I am sorry for the delay, but I was on vacarion the week you sent me the letter, and your request required much programming, data manipulation and editing on my part. Please disregard any. data tape sent to you prior to this one. I used the chronology sent to you on Nov. 12, 1985 to determine who was exposed, and I corrected some social security numbers and "conflicting values for birth and hire dates. I did not use the chronology sent to you Feb. 8, 1983 because it does not accurately reflect the exposures. The files are identified in the following way: COE5577: These are employees who were active between 1955 and 1977, and whose work histories indicate that they worked in either a 2,4,5-T or NaTCP department. The start and end dates of these departments are listed in the chronology sent to you on Nov. 12, 1985. ESS: These are employees who were terminated prior to 1955 and were potentially exposed to 2,4,5-T. See part Ic of my memo sent * to you on Nov. 7, 1986 for information on how these employees were identified. TCP: These are employees who were in the TCP accident study. I have included a female who contacted chloracne as a result of the accident, but wasn't included in the study. SUS: These are employees who were in the Suskind/Hertzberg morbidity study and were exposed according to either the Monsanto or University of Cincinnati exposure criteria. These criteria were described in part 5 of my memo dated Nov. 7, 1986. -Please be aware that Dr. Suskind used only the University of Cincinnati's "Exposed" and "Non-exposed" categories in his study. i 1 e iarilyn Fingerhut, Ph.D. 2- May 4, 1987 In addition to the usual header record variables that you are very familiar with, I have added the additional variables you requested: a Monsanto and UC exposure variable for those in the Suskind study, a data source variable for those in the B455 file who were identified as potentially exposed from a source other than their personnel record, and a variable to indicate whether there was a a work record in our computer file. I have also added a date of termination derived from 941 forms to those in the B455 group who did not have a personnel file. Since I combined so many different files using various computer programs, I made many diligent attempts to check that I was including everybody I was supposed to. I even compared my final cohort to the names on the three lists I sent to you on Nov. 7, 1986. Unfortunately, I discovered that there were twenty-six names on my current file that weren't on those lists. ALL the names were from the Suskind study and had a Jlossstnrjo exposure code of either 1 or 2. (See attached list). I could not figure out why these omissions occurred, but I can assure you that this current file includes all the exposed Suskind cohort members. The record format for the header and work records on this tape is in the attachment and the tape specifications are: non-labelled, 9 track, EBCDIC characters, density=6250 BPI, LRECL=97, BIiKSIZE=6208, RECFK=F3 and #RECS=63S2. If you have any questions, please feel free to call. Sincerely, Marcie E. Strauss Epidemiologist i , - o W %J . . . IN THE UNITED STATES DISTRICT COURT SOUTHERN DISTRICT OF WEST VIRGINIA CHARLESTON, WEST VIRGINIA JAMES M. ADKINS, Administrator ) of the Estate of Ralph E. Adkins, ) Deceased, et al, ) > Plaintiffs, ) ) vs. ) No 81-2098 MONSANTO COMPANY, a Delaware Corporation, Defendant. ] ) ) ) Deposition of CLAYTON F. CALLIS taken on behalf of the Plaintiffs. Reporter: M. Joy Springer J a m es M ay R e p o r tin g S e r v ic e CERTIFIED SHORTHAND REPORTERS R.R. 2 - BO X 65 EDW ARDSVILLE. ILLIN O IS 62025