Document 2qmMB8wojkaO9drRM3wjo6dDg

ENVIRONMENTAL PROTECTION AGENCY ChaobUe Toxicology Laboratory 4770 Buford Htghvay ChaobUe, Georgia 30341 October 14, 1971 Or. George Levinskas . Monsanto Company ' 800 M. Lingbergh Blvd. St. Louis, Missouri 63166 Dear George: Enclosed is a copy of the article on bladder cancer in the U.K. that I mentioned on the phone. Another article that discusses this problem is one by Case, R.A.M. : Tumours of the Urinary Tract as an Occupational Disease in Several Industries. Ann. Roy. Coll. Surg. Engl. 39:213-235, 1966. Does Monsanto have a cytology screening program? If this is not the case it may be prudent to set up a cytology screening program where workers would submit about a 200 cc early morning urine specimen once a year. The freshly voided urine could be filtered immediately through a m illipore fil ter, then stained by the "Pap" method and examined under the microscope, or It could be fixed in an equal amount of 507. ethanol and shipped to a laboratory and processed there. I do not think that collecting 24 hour urines would give any more information and would be a nuisance to collect. For the sake of completeness I am also enclosing the summar ies of two articles which I am sure you have seen. Both articles report some findlngs on Aroclor 1260 Lot AK-3. Let me know if you need any Aroclor. We seem to have more than sufficient for our kscudLes. ` Sincerely yours, enc : 3 Renate D. Kimbrough, M.D. A0M 006` 1000615 116 STLCOPCB4028029 tOtarr* ^LeuiOuJ.h , /`/J ~/Y6 ( 1 Asaler^Bt to advaa m ,.m. disposal. ;rnl " O'/. * >01 O. ta 3*9, ^` " ^<J * __` ` ** ' _ - The Lancet Saturday 24 July 1965 Cealsalaor-a, Witham iw, irst edatioa .irmsrologial fee prompt rt prevma ternadu 14. Soklocts U atcsle. The 1 assessed &T PS STOdied is :n-~Nsneaai WaaluagSea, , , ' | I ntnn s4 .-rets, arias- s mm mii< m X There are jjsun, &&I 'npffisw. -@ K-.NL | j ; | 1 [ i 3c=oJs=. Tbis ^^v^xag um- -f La^rawnei, : tt&gm im. 0*8-) | l ; 1 .frf f Rho* cat A^vUar? iscU as4 (fee fff-* c&A 6s ?nt4 aff F^curTracn ; yr\ unuou um AJeLaecU* No dte/&a.) 31 RdJd*k ra-rocai rsco* mt a/ pausnu.-ucuUiiy Fuje lx_ (T#fK. rta K.M. ' ' . | j ' 1 ' ' j j i seet fey tbs O^etrra, -i American :' trptuut hiT "33 ca -Tt 3. Strp^-ns- vo 2^0,feG3 9% t vrarrea'-a *KawU >* 'fitAtunoav Srv Yo** , . , j ) 1 : 1 F*41* o4 "tou^a ftsi4 k0 , t.L.O . a^ ipns vtJ pc?v>da e t-ndos ra*^' H-M* S'.autgmg^ j 1 BLADDER TUMOURS IN THU the disease stacked ersry one of a group of 13 workers ELECTRIC-CABLE INDUSTRY Joan M. Davos M-A. Ossx, Dip- P^A. . 5 - Frew rAc Btpammaxi a/ CimcsJ Katemvk, Rsyed Afwtdtn Hotfii&l, end Uuantse ef Can&sr Kuemtk, Lem^m, S.tTJ Ik 1949 Oa and Hoiks; Lavestigated th@ iaeidenct o tumours of the bladder is the mbb& Lsduacry ia Eaglaad sad ^"sies; this study w&j not ipastured by the industry, sad was based largely on data from census reports, dasth certificates, and hospital records. The fi&diap were communicated to the appropriate authorities and m the adostry La 1949, but at that dme the Rubber Maaufaeturfflg Empioyen' Association did not sanction pobUeaeea (Hmes 1945). The results were finally published five yars later (Case and Hosker 1954), and demonstrated m ocapsdoml risk among skilled rubber workers both ef eon-' oaenag tumour of the bladda and ef dying from this disease; these findings were compatible with the hypothesis that a risk was introduced into the industry when > certain rubber-antsoBdaru came into use s 1928, The produesea enpged on distilling l-oaphthylacune ia one p&rocuUr plant (Case, in the press). The average " induction-time " between first exposure the carcinoge&s and the development of the disease was 18 years; but some rumours appeared sritfua 5 yean, and wm after 43 yean. There was no evidence that this siducaea-ame was shorter in those with severe exposure, or longer in those with cotnparaarely slight exposure. During the rurvev is was observed that tumours had occurred among chemical workers engaged in mano- feerunaf die anrioadant mentioned, which contained 2-5. of &re aaphthylaaine of which 0-23% was* 3-raphthyUmiae, and this was the observadoss wh^' prompted the study of the rubber industry. _ The fuacaoa of annosidants is a retard the perishing" ef tto rubber ia a finished anode, and thus presort its strength aad eiastidry. They are among the choucsT ' agents added tn raw rubba to fora s rubber air, which' is then sump-dated under hm m form a sompsmd.' AaeroBdaaQ are frequently used in powder form, and are usually added to the nus is the proportion of om or two of this widely used rub stance ceased ia 1949 whes the parts pa hundred. Subsequently the compound .is danger to those nuking and using it was recognised. wmdM or estnddd to the shape required, and rubiectsd* Case and Hosker regarded this as a preliminary study, to tost (usually by steam) for the process of t-ulasramrien. and considered that a much more intensive survey of the If the anhosidant contains naphthylamines, they will rubber industry was necessary in order to ascertain whether contaminate the air of die room where any of. these the anuosdant m question was in fact responsible--ind if operations are carried out. They may be absorbed as so whether it was the sols agent--and to measure the risk powder or vapour .not only by .the workers, aeruafly and study io dynamics: Such a survey has never been' handling the rubber, but by anyone in the room. . made, and for infomanas about the background the Is 1944 the rubber industry purchased 1410 tons of disease we muit turn t@ the survey of occupational anriosdana of all types. At that rime the indusmy bladder-tumours in chesucai workers of Case et ai (1954), employed 77,000 persons in over 300 factories in England * although * cannot be certain how dosdy the findisp of and VTalet (Board of Trade 1952% this survey wiU apply in the comes ef a different industry. The swvey was sponsored by the Assodarios of British ' The Electric-cable Industry Chemiol Manufacturers, and was concerned ith the la terras of sua-pwer, the eleeme-cable mduicry is half the aoralhy and morbidity from bladder rumours ia a group sue of- me rubber indusoy, and u is cawenuxced mainly ia ei f444 4y&tuS workers in England and 'S'dea. Lar$e ftetones us Greater London, Lsncatlure, and Cheshire, The results stowed that by 1952.1 tn 10 of these mea had already developed bladder rumours, and that in time tfrfbfh there are fanones ia other counties. At present 31 eotapaojei in Eneiard and ^"ales see parties to the Joint Industrial Couaol lbs the mduicry, and these cootrol about 40 factones. . the incidence was expected to reach 1 in 5. These ' Elertne ables may be ro=ritjrij cables--c-- lubounna tumours could be attributed t| exposure ts s-naphthyia- or telephone ablei--or peo/r ables. ^"e ire concerned only aiae, i-tuphtnyUmiae, or benzidine; 5-naphthylamme with the latter because commuruesoon ables do r.os usu&Uy being the most potentcardnogeo. These substances may comaa rubber. Poaer ables varv m ure according re the readily enter into the body whether they are in the form of powder, liquid, or vapour, for they may be ingested, absorbed through the skin, or inhaled. .. The risk to the workers increased with the nouat of exposure, meaiured by either duration or degree of voltage they arrv; the smallest contain a untie conductor wire ahilst Larger ones cootaio many wirrs imndcd together. la most power ables the conductor is imulaird. and (eserpt us ables carrying very high roJtagei) rubber as the uiual insulat ing material until the recent introduction of thermcplasoe materials such aa poi\rchviene. The iniulaird conductor is exposure in various operations with the rubsrances. Thus covered s protective outer sheath, and rubber remains the at one end of the sale i small number of rumours most suitable material for this math a certain types of able-- developed among women such as fitters and plumbers, j|, house--ssrtng and cubic trailing ables. who handled contaminated machinery or worked in con In 1W9 the eleetne-able redusay used 10.500 tons of rubber. taminated atmospneres, and at the other end of the scale This was yy O', e t=U rubber oocsuoved re ih Ui--4 ^ .7404 Knnnfii6 11 V- 3--* STLCOPCB4028030 144 JW.T 24, 1965 orarKAt kittens tSB UJSC3T --sracnos T- 1 i tv-1* t t Tem& , mm " H T-- ` u m swno r? tum ilksm "i- - m a IS 8 ms -- JCiordeen, aad only a with of the ameaa* used ia tils fesrure of tyres ao4 rub t Central S actual Otftca 19321 Aaoosjdina ire essential tagrediests in the eompouamag of pub bar uied for uuuuung or covering tLrarie aeUs--<hs Murm ssuoDdrsfia that are used ia the rubber industry. TMa mnmndju.1 withdrawn us 1949 was popular ia ta* obk mduroy, $ad had beea ia w sides 1933, and poistbly earlier. This Cats sad its unpliaocos seem have,escaped sociea for a deads. Lsjs the possibility of a bladder-rumour hazard ia the obis fadusery was meatioogd by ta Book Aiteciatieia of Ureiofs* ed Surgroaa (1941', aad 6? Scots .1942', md um eccurrmca of dathi from bladder rumours among cable worfern was noted by Cam sad Davies (19431 Ye, oair arte the publkicy which fetlovod the inquest oaC. L.a former cable works? woo died ia January, 1943 (Lunerr 1945a), was much snenboa paid to this risk, sad is seams Ukaiy that is seventy is stiU ass fuUy Dwatka Lb GabU Werhm The dsn s&alyaed her were obtained by eraminiag ail death ceradates on which papUIomj or areRB3 of th* bladder mss ocasoari as a cause of death of mala is England sad 'Tala from 1943 re 1944. During tha 20 jars ths ecupaoes gives os 65 of these cmafirates radicated a worker is the eiecr-.e-able industry; is the ise period 113 such eerdfiates related to rubber workers. Table 1 gives the duohbudoa of these deaths by date, sad shows that in both isdustrul groups the auraher of deaths has increased in each successive quinquenartm. Dt&6v4&aJ<&s ed 4by o&ajr ef j*ffeA4eas^ The geographical distributjoa of the deaths is thews ia the Mcomputymf figure; aaarty half *e able workers favtd is the Greater Landes am, whereas the highest ganoaenbofa of rubber workers were in the Midlands rad the North-Vest. la the past there has bees a teadary m assume that iadusoul bladder turnouts cooeersed only tUnieam ia the North of England; a study of the map wsd show thsa this ts am the ase. ' If we k&gw the aumbers and ages of all male workers engaged in the manufacture of deems esbies during the mass period, we could aleuiste m tspteiid number of bladder-rumour deaths to compare with our aStsrstd number of 63. Uafommatriy this is not possible because the only courts of such tafermanen art the Reports of the 1931 Census, and the occupation tables ditim^nth only a small group of some 4600 " Beane Cable and UTre_ .Machine Drivers, Settm-up and Assisuna '* (coda 233,234); ail other blefeetorr workers (number- S o*? 30,900) form part of heterogeneous groups of employees in the " Metal Maattfecure, Enginssring and Allied Trades ". la most enm the occspeoo&s gives on the $3 dash ctrnffote* indicate the able worker*' >atus(c.g., Isbourer, able maker, foreman) rather than the depameaa in which they waked, and so afford few dues as re whstha the deceased sea wm ia contact with rubber. We do, however, know the histories e S of the men, sad sS but 1 <& these had had mas with rubber. It must h ranembfred that eiposurt on occur without the actual handling of rubber; this was illustrated ia the case of G. L., whose recorded ecsspaden of wire straadiag was probably innocuous but who incum-d inddeaoi opoeurs when he visited the rubber departments in tus facasy ia the course of fire-watching duties (Lancer 1943a). The figure of IS is Eksiy re be a considerable oader- otimste of the number of men who worked in able feaories and rubsequeady developed bladder ruasun, for it esdudes three groups of ora: (1) Those, such es G. L. who leave the industry ad are see teotbfd on their death orufiates as cable worsen. Such cam do as* usually come m tight unless patients hare been $umseeid about their past iobs and it is possible to link their eue-biscorira with tneir death certificates. (2) Those whs develop bladder rumours but whose death eornheatea do not memos this randitteo. Cue et &L (1934) feuvd that 19', f patients with bladder rumoun noofied by hospiuta and kaavi-a to be dead had oo mesoan of this disease M their death certificates. (3) Those eh have been suseeti/uilv created and sre still Being. At the Royal Marsdes Hospital alone eight tuck pauena have been treated. Similarly the Acute of til must be an understatement of the number or tumours among rubber workera, and there can be no dibt that the iniorrtuuon available about the number of eases of industrial bladder rumour us the able and rubber iodusm a woefully inadequate. Bladder Tumeun as a Cable Ftetory Attention was first draws to these raws when a former worker it a Large cable-factory m London was treated for rumour of the bladder at the Royal .MonJen Hospital and reported that 2 of his former workmates had received similar treatment. The factory had reerntlv been doled down, but theie 2 men were traced; it was found that they were alixe and w<||, but had id the past been treated for papilloma of the Madder. .All three men had worked m the rubber mill, and subsequently other cases from this department came to light. Fnnn6i7 yctr 24, ?'rf IirMs&s-rficUs. l*Vll rsis-u rra>n TU ! a bio, a 1949, Mi tbs rubb rSinr wsn aasarada stabseque rad the; drparaac Tha i tad n a Bss of ms tit That w ' "sttf" Mn 15 wvA tho iiy iss^ kiit Tsbk s of ebs L' lOyanf Vila sh occurred 1944-44. frota sac dafferase re cbm already c temour, AS 6 acre tha are given sgt of 60 the end 4 deaths recurred No de. among i How ever ` 1-5 yesn sad that group sot was m II No cot Taat l 3 3 5 6 1l8 ADM 006447 STLCOPCB4028031 nc* tANcrr ho iaworker* the hi (hen ... Midlands rt a tendency ipumed only of the-=P jvjie workers , during the ; RUfflhe? of . it oittrctd (.H beaause ,, Reports of . distinguish . Cable and Assistants " ,.-j (mnmbert groups of -scoring and she 33 death .labourer, yaraneaa in to whether i*CT. ^ do, s. gad all but It must bs -at the actual % the ease of ding was . exposure his factory in l-'65a). mble uaderr'.-'d in cable Iks tumours, f and are aes " . rtm. Such r -ts have been e.i ta Ua& their - whose death > rt si. Cl954) ' rs noaAed by s : this disease - : iad sre roll ' >ueh patieao ''rrsate-tesi 1 Jrters, And -'Ublc About -"--our m rho ^iuate. gl,Wy a s former - treated for ^'P'Ui and ' received orT* closed *2 that they ' 'rrstedfor - worked in k* frora this ,.T 24, 1963 OtldtXAt ABTICtll TKS UjeCST 143 T-. a u--rua ee siars vra unctm o? mt*o$cu or uru weaxms bladder tumour among workers is other departments i^ yew^l -f ,, --- 1| i _ ' t Ei Sp.,. m mn . Mre. ; Tank >t J* tms factory, but 6 am have come to light, and three oi these panears hare died (in 1939, 1934, and 1933). 2 m th men concerned were members of the scientific stad &rm and Jpot some of their time at rfri particular itwivea i^s-is iei>a-- ISAJOX- .. ,_ 1 S > T -- a V i ^ *; s I .1 -1 # .. 6 17 s :s : 24 <n .. 23 factory; l man ni a labontory teehnican; l wonted oa process of \-ulcmmuoo, and 2 n-orfced m the stranding department. The first 1 are beiieved to have actually handled the anooxidant; the vuiomser was presumably Tl ) U eo 1 u s* ; is* n^itd to vapour from rubber compounded with this substance; the itraaders may never have handled rusbex, The faaory manufactured rabbsr-insulaied power bttt it is known that one of them had occasion to go in mbits, and used the articsadaaj referred to from 1933 ts 1949, and possibly earlier. The operations earned out in the rubber Bull included the weighing out of the additive that were mixed with the raw rubber (these included the anboadant, in powder forth), the mixing proems, and the subsequent rolling of the rubber compound ts i required thidtnms. The coadag of the conducts? wire with rubber and the proems of vulonmona wm earned out in other departments. the rubber departments, sad the other probably did Ukewisa. The period when the anoosdaat was used included the whole of the 1939-13 war, and it is likely that there was increased movement between oeparaeucs sx this ame. Indeed, h would be diSeult to exclude exposure in the ease of anyone who worked as this factory during the war, for a one stage the rubber mill served as as air-raid shelter because it was on the ground floor of one of the strongest huiidi&p of the fantasy. The firm eonesrsed pv assess o the reads af former workers st the factory, and from these reads a list of men said to have worked in the rubber siU at some time during the yean 1933-49 was compiled. There were 139 such men excluding foremen end other M staff " workers. Many of theta also worked in the mill. DUemsim . The results shown above strongly suggtss thas the risk of eonsneoaf occupational tumours of the bladder, already knows ts exist in the rubber industry, w*** mra the decoie-eable industry. One of the causal agon S %lmsn CSS^Slftiy sa of before 1933 and/or after 1949, but we are conosaed only eeased in 1949, but we have no a&surucs that thsi s the with the length of their exposure ts the anuoadant, and ealy source ef dasgs. this length of exposure is dened as the period of sense The severity of the risk demonsvated in ma gwp ^ in the mill between January, 1933, and Deeoaber, 1949. rubber miQ workers should bdp ts dispel aay doubts ' Table shows the yean of birth and length of exposure above the ntcessiry for tradng exposed workers md of the 139 mem; is can he sera thas 30 men had eve offering them cytologies! seeming tests. Thm is as 10 years' exposure, Examination of death csrdflcscea for Esgi&sd md Vales showed that 4 deaths from bladder tumours had reason ts suppose that the epidemic of manure u ths faaory is unique, fox wo know of dusters of 3 or sm eases at some other factories. It is possible that thorough occurred among the 139 men during the 19-year period searches would reveal cases it most cable ad rubba 1943-44. The expected number of such deaths, calculated factories that had used this anooxidant. Hitherto mm from naooaal age-spemic rates, was found m be 0-2. This laaory managements have oot been conscious of this m3 difference is highly significant (rioO-OOOl). In addition to their workers, and many cases of industrial bladda to these 4 deaths there are the two cases of papilloma rumour have gone unaooced by them. No Arm shook already mennened, tasking t mol of A essa of bladder assume that its workers have neaped this risk uak& > tumour. a scueiny has been cade of the causes of death of ai All 3 cases occurred assag the group ri men with present and former employees who have died during th, more than 10 yean' exposure, and deoils of these eases past 10 or 20 yean. Bladder-tuxeur is not a commot are given in table in. Ah the deaths occurred unde? the cause of death and the number of nararaily-oceurrim . age of 39 years. There art no grounds for believing that cases that may be expected to occur under the age o ; end of this epidemic has been reached, for 3 of the 63 is very small; this ts illustrated by the expectation o ` 4 doth* occurred Ust year, and 1 ef the 2 papillomas 0-2 death^ among the 139 auh workers over a period o a few months ago. 19 years. ' _ Sfadesths &c bladder tumours have occurred so far . ' It seems inevitable that forth' cases of this disease w twg th 109 men with shone? periods of exposures* occur as the result of past exposure, but at least e mx Hwem, it should be aoced that 23 out of the 33 men widf he^e that early diagnosis will save or prolong the lives c 1-3 yean' exposure did not enter the midunoi after 1944, some of the future victims. and that rumoun would be expected to deveiop is this The probable industrial origin of many cases c group some 10 yean Ute^ than in men whose first exposure bladder tumour among cable workers appears to hav was m 1933. gone unnoticed not only by factory managements, bu No oomprah&sivt search has been made for case of also by the doctors who treated these cases. 'S'e hav tails n--iuido r.'Moiu u* at-sets.-ua wesutssa Tw 6^ : Bm. I ^ \&e QVtei sa ^rr.) \ l56 is |1 l199)12--53) , 1in*5#4 |1iI M$ 191) ,i Airw , 1[995Va2---esS-a U/U*C*srQ |, 19^4 ** 1 19^9 Afa & ,77.) IS W 5) noted that of 65 bladder-rumour deaths that ocrurreamoog cable workers some are derjuttly Ixmwa to be c industrial onpn, and yet none of these 63 men cerofled as dying of industrial disease. The most Ukai expLmjooa for this omission is that the desths were ac reported to ooroners as being of possible industnii or.g-beesuse the ceruriioK doctors failed to oouce this aipcs Knnnfiis 119 A 0M 0064 STLCOPCB4028032 JULT 24, \WS oiau4i *ir:eixi Lu*=r? As tmfiprcunare result 0/ tbls Udl of mraui ossf doctors b that in many aitucn where the c*ei worker* snotled to teseht far a presmibed iadujcul dims# 0> 39, p8psUema~of !h'BUjicr; aobody &dv-itd th* aa that thsy Sff|iW| for ctus benefit, sad u&asso- mr? tefdibif ms? hsv reruJesd; s ij teh'ered th&t tea ted ted more than 10 years' exposure m the ennexidaac. nd 6 of these men developed biadder rumours. So nnq wars observed among 109 aid workers with therm? peseda of exposure, but i further eases occurred wtjrsen a other parts of the fcemry. In 7 of die 12 am the disease proved saL ifS4 uaoi sqdl9J eai? cabin wott was greatsd &ac& As W am of cLa Laduafft&i dise&sa can a Bght s nabt ef claims fa bang suds retnwptetrvsiy, oms by cabla-thenwiv sad unt by widow* (for m2u)trul widow*' pcatioes). There b bo certainty that sll the subronea rerponjfbl* ae this risk have been identified *"^ withdrawn; only a hiS iavesagiooa eaa ehimdais r<t< point. , ^ tteali I3a o thmk Dr. t. E. Ttegumas Hgurna. duecas T spXB*s <d deucy mnrva. as Mr. D. AL Tii'u, amnia* To s Learn ertest dte lack of awaream spplka ts at bladder tumour among rubber worsen, ssd the dearth at rtswdx and published iaformanoa are largely responsible for this ignorance. Disqum suy bo felt artx eeywsast. keyai Mandcs K01 vtm, itxx pc-annaa a uumview paowaa 14 ua amiol ramds; icrwy etner orwoena !tt iSar smwiui: use BiMirnawfli oi 8 ^rgv cioic^ayacf Sr t ready coevann^o sad roe pro*, Omg tonu ?wares 1 &&4 tdc <d Later fee providing access ra isar noeras s{ , the recent response of the Medial Research Causal (Law? 1953b) ts the request for as iadrpeades kavonganoa into bladder rumours ia tbs rubber industry:, Ml only has the Council declined a any out rush aa." temtigsaca ioeii, but it baa suggested that a sort Ifajtad trudy of the inadeacs of rumours abould bo mads by tbs Rubber MAnuracrunag Employers' Assodadca--<a tody which opposed the publishes of the original study f this problem, tad which has sot published say of the valuable iaformshoa it must possess from the Hot ? yean' results of its eyteiogiol screening servie*. The baaie reason why * thorough iaverdgadon at the j rubber (sad cable) industries is sought remains the ssas ss wba this was fins proposed ia 1949: there is . ef Tiods flvm Hud Rnv, of ^ < Vos. 11, Tnda A. Suasa. r ttdi Inws *wwi W L'rwww<y S*rw*w (l**l) Jr. }. tIni. a. l Cms. %. A. X. Tks Swanads Baa et Mrcaui ABmai Banmm, IMS iadatrail -- Oanm. /. (loan . y pw. . diai IS. S. _ Katut. X L (1SS4I X S. _ McDwa^.D.I..PaarMa.J.T.aWslr y.4sW.MadH.n. CmaU itwmaA Qrtm (19)21 .VAanu Ayiraa &t Saooc& Um^, Osadnci J. (194)1 Suusacxl Smcisa a ids ^kusiaey ^ MUdUd Smliira K Ssm as SaaBi). UL Ca)aia, . he--Mfttm*m)uj t1. 121M0a, .S2S. . Soa. T. t (1942) Csmuspsa md Qaadi To* ttessa tl JM Amtaaa AmsOT^ ThmitlMn J. JO. . * emaisty that ill the dangerous su&sc&aea hare tea/ idasfied sad withdraws from use. This doubt has bra; neagthened by findings such as the esadauiag rat is; Aa number of certified deaths tea bladder tumour is- rable end rubber workers. * It has been seriously suggested ths the naphthyiamm mGHAinruDE pulmonary EYFEETOSION iKsm StKcm MX F.S.aX PXCP.O, FJLMS. oosBUnn w Ksmcsti re ns tsum raesg unrest of esrtaia aaboxsdana msy not hare bees the only dangerous coosatuess of these products. The my high jasdests of bladder rusours ia one poup of cable ?. K. Ks^tma MO. Fm Masan Lm> MJ3.1 workers leads some support to this suggestion, for these aea were in contact with an anoomdant containing s men 2*5% of naphthylamine* of which only 0-25'L was the isomer, so that their exposure to these ordangms wss almost certainly much less severe than thar of groups of chemical workers with a similar rumour incidence. The implication is that we may have to deal with a completely new and unsuspected class of chemical cardaogeas. Oemmesm (1965) discusses the feet that the survey of bladder rumours among chemical workers was made only long after the risk in this industry had been first suspected, and commeats "... it may $e difficult to future workers understand this so many decades should pass before a sesQLsbffiily MMd tv&Jusdos of risk was earned out *'. It seems U.mo feiy that this remark may apply equally to say eomprah^wre study of the rubber adustry. R. S. Hoom B. D. P. Rao M.B. Ptara&, MJLCJ'S. MS). P.ChstX, O.CJ>. eoMsum ssvub m Mssicom rsorusa so piTEomov efei Dirmmts General, Anfad Fsrua MtdUM Ma, Afsw Oslb', if, i/idid Rntta et tL (1936) first reported that people living st high altitudes is the Peruvian Andes ted moderate pul monary hypertension. It was ls evidem in temporary residents with s year's continuous stay at high altitude, and most evident in piuents uith chronic mountain sickness. Their findings ia permanent residents of the Peruvian Andes were confirmed by Sime et aL (1963) and by Pedalota et aL (1963) and,by findings m the conunenoi United States by Vogel et aL (1962). * ^e htvo been concerned m-'itly with high-aldrude pulmoofty hypenensioo ia temporary residents in the Htmaliyaa. The following is an account of our experience A high modeacs at bladder rumours among skilled rubber workers was demonstrated a 1949 and may have been amted at least ia part by Va anuoxidant used between 1928 and 1919. T^ui high incidence has never been fully investigated. Factories nunu/acrunng electric power cables also used this antioxidant. Examination of deatn certificates for England and ^Tiics for the yean 1945--64 revealed 63 cases of bladder tumour *here the deceased waa described as a cable worker. In oog large able factory >0 worker* in the rubber mill of 102 cases. Predisposing Factors The exposed population consisted of sea agtd between II aad 47 years. Foe 98 temporary residents from tex-lerel the vulnerable alriruda began it 11 i<30 feet. Foe I person it wss 6000 feet, and for 2 persons bom and brought up st in altitude of U J00 feet the vulnerable altitude wss I2J00 feet ind I4AO0 feet I mao was s load resident living st 12.000 feet. La 61 men symptoms of pulmonary hs-perteniion begin after, five io forty-two months' stay st high sitituie. la 7 men this hjgi-iJurude stay was continuous for 6ve to us oauhs, and in fVW er to 1000619 120 A0M 0064 STLCOPCB4028033 w*wou*rr a wm nUtMACousax 17, 656-461 (IfTO) Comparativ Toxicologic Study with Polychlorinated Biphenyls in Chickens with Special Reference to Porphyria, Edema Formation, Liver Necrosis, and Tissue Residues 3. G. Vos anoT; H. Kocmam Institute ef Vnerimmy Hthobfy 0ml the Institute vf yrterinmy Phm-m&nk^y W Textew^gy, Unsteruty / UtretMt, Vtroth!, The Hethstismti JtwwfcBrf Nctentk^ J, 1969 y\ , . * f I H)' .n if * i f.ojIC .s^ UHtf is whfor r ,, k tr*' % L f.MTUU r-.TJf3 the JSCT3, ...Ugw st Comparative Tesieologie Study with Polychlorinated Biphenyls in Chickens with Special Referenca t Porphyria, Edams Formation, Liver Necrosis, and Tissue Residues. Vos, J. G. and Kooum, J. H. (1970). Toxicol. Appl. Utartmcal. IT, 656-661. Tn s comparative 60-day oral toxicity test (400 ppm) in chickens, three 60^<ft)orinatd commercial polychlorinated biphenyl (PCB) preparations were used: compound I (PhenoclorDPd). compound II (Clophen A60), and compound 111 (A/oeior 1260). Using mortality, mean survival time, (roan weight, and pathological Hcrvstions (hydropericardium, abdominal, and subcutaneous edema and centrolobular liver necrosis) as parameters, a significant difference in toxi city was found between the compounds: compounds I and U showed the highest, compound III the lowest, toxicity. Microscopically rentrolobular liver necrosis was found in chicks fed compounds I and 11. Atrophy of the spleen was found in all test groups. Chemical porphyria was found as a general PCB effect: increased fecal excretion of coproporphyrin and proto porphyrin ar.d fluorescence of tissues occurred in all test groups. Additional experiments with compound I (2000 ppm) in Japanese quail and rats con firmed the porphyrogenie action. Gas chromatographic analyses of liver and brain of dead chicks pvt PCB levels that varied between 120 and 2900 ppm. The relationship of hydropericardium (chick edema) ar.d liver necrosis to the differences in testdty observed between the technical PCB mixtures is discussed. . In recent years the presence of polychlorinated biphenyls (PCB) has been exhibited :n Ash and wildlife ip many countries, including the United States. Great Britain, Sweden, and The Netherlands (Jensen. 1966; Holmes tt el., 1967; Holden and^Mariden, !**. Koeflan tt d~, 1967; Riscbrough rf el., 1963; Kocman *t ef., 1969). ^CfBtmerml PCB preparations are oily fluids coosixiing of a mixture of dilTetent chJoriuted biphenj It. These chemicals are extremely.ftable with very low aqueous solubility. They arc used as lubricants, as fluids for heat transfer and dielectric medu. in protective coatings for wood, metal, and concrete, and for many other application* Which of these applications has contributed to the present widespread environmental Contamination has nos been elucidated. The occupational hazards in the use ol I't 0 have beets known for yean: normal handling of these compounds lias not given nw 10 great difficulties (fnsh, 1963). ' Animal expenments with rats and guinea pip have shown that the ingestion of PCH &34 I he PC DP 6 15 t wkcT<U j .nlinu they were I he birds V*Ti>Up II. ..miroL I lw> <M-ted ol 3 vuretully 1 into the ra jnJ the a gr.'up II 1 b> the l*C i!i warded At nevr r ted le on tcnuiscd' .1 ihe llui *n.l -uKi liver, -pU-< ventiiHial ..w Urt-ei*!.id with r \Uiun hh vtudies * 1 llu.'fvw. cr. tweiiee ol 1X100620 121 adm 000*1 THu^3:rwvcr "tts* Although rpport it: ent effect e oagmam thoM . auffl eoBr ier. 1967). aganium TQoa ob agsw'um rat. which easmioa ss &a tug* as admits* is uria# hat aalorrhtad aad I ! 1 j j i j mJ support mattiura nsss is no. L Row &sd JR) metafao/. .Wed 27*. iemijtry ea4 -yrven. A. V. 4- Sponger, i infvajon on I . . ' _ / < fwc^aa? am nfUD m&asuaxwr 15, 617-43) (if?i) * Dermal Toxicity Studit* ofTtchnial Polychlorimtnd BfphenyU and Fractions Thereof in Rabbits J. 0. Voe and R. B. Bczms kusitism ef Yrrmmmy FmMctr mi barium f Yurrvmrj Umnrvr *i Vtrrc*. BtUuram 171, Utntkt. 7V aW Tomiotr ' cswW Ckrsrtse J, 1979 Dermal Totin'ry Sadies of Tochaisal Polyehformsted Biphenyls and Freedom Thereof in Rabbits. Vo*.J. G- sad Sums. R. B. (1971). Tssieol. Appi. fh&mscsi. 19.617-6)). A significant differenca in toxicity betwn 3 polychlorinated biphenyl (PCB) preparations was found ia prior study: Qophaa A 60 and Phenodor DP6 showing the highest. Arodor 1260 tht lowest, tonicry (Vos and Koetnan. 1970). A subsequent study remkd the presence of tetra- and penuchlorodibeaaofuran ia Phervodor and Gophea (Vos etsL, 1970). Io the present study, application of 11S mg of the ) PCI's (5 timo pa wk. for 38 days) on the teds skis of rebbtu aiso resulted ia differences in toaidry. PCB-tndussd skin teioaj were hyperplasia and byperkamtes of tht epidermal and follicular epithelium. Kistopathoiogy of the trier induded smrolabutaf defeneration. esatrclobuiar liver cell atrophy, focal necrose. and cytoplasmic hyalin degeneration. Definite hyperpLasra and hypsrtaatests of the follicular epithelium of the ear skin were seen after the topoi application of fractions of Phanodor and Gophea eluted from chremstograph* columns with 23 % diethytetha' ia bsaane. The (maim from Arodor caused a minimal hyperplasia and hyperkeratosis of the follicular epithelium. PCBindused kidney lesions were hydropic degeneration of the convoluted tubules and tubular dilatation with the presence of casts. Thu dilatation was demonstrated also by a significantly increased relative pwcantap of the diameter which corresponds to the spass of Bowman. Morrow, thymus atrophy and lymphopenia were found. Fecal copro porphyria and protoporphyrin excretion was inereasad. Polychlorinated biphenyls (PCS) have been identified in tissues of fish and wildlife in many countries (Jensee. 1966: Holmes rr a!., 1967: Hoiden and Marsden. 1967; Koemaner a/~ 1967; Risebrough ttel., 1968; Koeman rr a/.. 1969: Jensen rr of.. 1969; Duke tf 1970: Presu rr a/, 1970k * PCB preparations ant extremely stable, oily fluids with very low aqueous solubility. They are used as lubricants, as heat transfer media, irt protective coatings for wood, metal, and concrete, and for many other applicasioru. Which of these applications has contributed to the present environmentalbnlamination has not yet been established. Inhalation and feeding experiments ut'rats with 65*j chlorinated PCB resulted m liver injury (Drinker rr si.. 1937; Bennett rr aL 1938). Liver damage and skin lesions have been described after inhalation, ingestion, and application to the skin using rabbits, guinea pigs, and mice (\ on Wedel tt si.. 1943). Hydropencardium occasionally accom panied by abdominal edema was found in chicks fed PCB (McCune rr at.. 1962. Flick 617 Fnonfisi 122 AOM QQbk5 1 STLCOPCB4028035