Document GK9yzYZN29ox4o81G8KKrK56n

ENVIRONMENTAL PROTECTION AGENCY Chamblee Toxicology Laboratory 4770 Buford Highway Chamblee, Georgia 30341 October 14, 1971 Dr. George Levlnslcaa. Monsanto Company ' 800 N. 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. Docs Monsanto have a cytology screening program? If this is not the case it may be prudent to act 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 mlllipore fil ter, then stained by the "Pap" method and examined under the microscope, or 1C 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 Che sake of completeness I am also enclosing the summar ies of two articles which I am sure you have seen. Both articles report some findings on Aroclor 1260 Lot AK-3. Let me know If you need any Aroclor. We seem to have more than sufficient for our ^studies. ` Sincerely yours, enc: 3 Renate D. Kimbrough, M.D. QXSio AOM 1,000615 0Q61 116 WATER PCB-SD0000033966 r tO^crr . ----- ~T ^ * , /yj ( 11 iUtim aa ..m. disposal. :rfti u Made* j:crn" m O't Ml o. ta J64, '* * ' ** * -7 The Lancet Saturday 24 July 1965 Ceatmiaorw **~i Hi Tmt --. first ediuoa .arsarolopol for yraapi st to proven* uriodiux 14. Sublects la alcslk Tha t umu^ k T-t irdied ia Kanonal ^nhington, . , ! | | Him aa4 ! sitM, sAar 1 sn oeted a -X Then in l;*-*-.--r tod -rtsruamev aa H_\L ImL This I ; ; I I [ I | -eluding 1USB- i laboritanet, .- tad a 1964. n-> I 1 [ af Uiv cal AdtUery ' ucU o4 ill 1 - frrs can It ' sntid esrtr : liramcn | jontiauout um .:X AJiucdaf : No charge.1 ' i at It edit dew 'rugaliKt*. ; me a/ ptuenu. j .ueuiaily luge | .uua u. (Tie*- K. Crtm H.M. : ant by the ( OS err*. the -1* American : trphnii ban "11 oin van ; 1. Havanata 290,60) is ' ai ia erarres- j ai lUuU be | rp u-uunoaa i haa Yoei. : 1 Feeding ted awium ha 14 J 1 . l.L.O , arul thmald ipone* alJ |ianda * nandiap maal- 4-M. Juuaavr j i : BLADDER TUMOURS IN THE the disease stacked every ne of s group of 15 workers ELECTRIC-CABLE INDUSTRY _ Joan M. Daw MA Oaaai., Dip. FJA . From iKi Diperrmna */ Qitmeal KmtmxA, RxyW Afwtdne Htipiul, 4iW Iaibmu / Cutetr Kutmtk, Ltniut, S.VTJ In 1949 Case and Hosker investigated the iacideaca of tumours of ill* bladder ia the rubber industry ia Eagiaad and Vales; this study ru not sponsored by the industry, and wis based lirgely oa data from census reports, death certificate!, and hospital records. The findings were eoBUBuaiatcd to the appropriate authorities tad to the industry ia 1949, but st that time the Rubber Msaufsetur- enpfed on distilling l-uphthyUmine ia one pardculsr plant ,'Caie, ia the press). The avenge " induction-rime " between first exposure to the curinogau and the development of the disease was 18 yean; but some rumoun appeared within 3 yean, aad tome after 43 yean. There was no evidence rh*e ik, tnducaae-tune seas shorter ia thou with severe exposure, or longer in those with eompanavdr slight expomam. During the survey it was observed chit rumoun had occurred among chemical workers engaged ia manu facturing the aatioadant menhoned, which contained 2-5*. of free aaphthylaoinc of which 0*23% was* 3- fljpbthylaminc, aad this was the observation whidi' inf Employers' Association did not taaetsoa publication prompted the study of the rubber industry. - , (Tones 1965). The results vert finally published fist years The fiancrioa of aarioxidaaa is to retard the perishing later (Case aad Hosker 1934), sad demonstrated aa occu of the rubber ia a finished arnde, tad thus preserve ia pational risk amonc skilled rubber workm both of coa- strength sad elasodry. They are among the chemical* tnctinf tumour of the bladder aad of dying from this sgeaa added to nw rubber to form s rubber mix, which' disease; these findings were compatible with the hypothesis ia then manipulated under hem ta form s conrpovnd. that a risk was introduced iato the industry when a cetaia Aactoadsaa are frequently used ia powder form, aad are rubber-aatioBdsnr came iato use ia 1928. The production usually added to the mix ia the proportion of one or. two of this widely used substance ia 1949 when the parts per hundred. Subsequently the compound .is daafer to those makief sad usinf it was recognised. _ mmddti or umdid to the shape required, tad subjected' Case aad Hotker regarded this as i preliminary study, ta heat (usually by steam) for the process of t-sdcamtotien. and considered that s such more intensive survey of the If the anoondint ***>%;*, naphthylaminet, they will rubber industry was necessary in order to ascertain whether contaminate the eir of the ream where any of. these the aauoxidaat ia question was in fact responsible--ad if operations ire carried out They may be absorbed as so whether it was the sole sfeat--and to measure the risk powder. or vapour .not only by .the workers, actually aad trudy its dynamics: Such a survey has never been' handling the rubber, but by anyone in the room.' . made, aad for information shout the backfrotiad to the Ia 1948 the rubber industry purchased 1410 mas of disease ' must turn to the survey of occupational anrioBdaats of all rypes. At tbit time the industry bladder-rumours ia chemical workers of Case et aL (19341, employed 77,000 persons in over 300 factories in England* slthoufh we onaot be certain how closely the findings of aad VTalca (Board of Ttade 1952). this survey will apply in the context of a different industry. The survey ns sponsored by the Association of British * The Elevtrle-obU Indusoy Cheatiol Maauftcrurcrs, and waa concerned with the la terms of etaa-pewer. ike eJtctne^abl* industry is half the mortality and morbidity from bladder tumours ia a poup tilt of-the rubber industry, and it is cancmtraced mainly ia of ?444 dyesruff workers ia Eafisad sad ^Cales. The results showed that by 1932, 1 us 10 of these mea bad already developed bladder tumours, and that ia time i Ur^e /ketones us Greater London, Lanashire, and Qicshirv. thikgh there t:e factories ia other counties. At present J1 consp'aniet us Enpiind end TTs/es are perues to the Joint Industrial Council for she industry, snd these control shout 40 fietones.. the incidence wu expected to reach 1 ia 3. These ' EJretnc ablet msv be tammymtjtijn esbles-^g., subounne tumours oould be annbuted t^ exposure to s-naphthyls- ' oe telephone ablei--or p*=<r ablet. V* are concerned only mine, a-naphihyianune. op: benadiae; 5-iuphthyIamia nth she Isrttr beesute commumcsoon ablet do not ususiiy bring the most potent<cardnogea. These substances may readily enter into the body whether they arc 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 mourn of exposure, measured by either duration or degree of. exposure in vanoua operations with the substances. Thus conuia rubber. Power ables vary in nee according to she voluge they any; use teullcit contain t tuvt'.e conductor wire *hiltt larga- ones contain eunv wim smndrd together. In mote power abler the conductor is iniuUtid. and feserpt u* ables arrv-uig very high roJuges) rubber at the utual insulae* ing tnstenal until the irtent introduction of ihtrmoplaioc tEjttmJt tueh u polyethylene. The uttulattd conductor is covered with * protective outer ihcaib. and rubber remains the at one end of the sale s small number of tumours mots suitable material for this iheath m certain types of cable-- developed among workers such st fitters and plumbers, .g., boute*wirtnf lod feaiblc uailing ables. who handled contaminated machinery or worked ia con In 1649 the electne-able lodusary used IOJOO tons of rubber. taminated atmospheres, sad at the other end of the scale This was only 6*, of til rubber cocuumed to the Uw*--4 y* 7?4 Y-3- lionnfii6 * n WATER PCB-SD0000033967 144 JCT.T 24, 1945 Oaionrat ASTICtlJ ua uhctt The geognphial distribution of the deaths is shown in T" IMS---e IVSO-M tiets*os->i* Taad 1 MWdf-a -v" ' ' Cam wa a liosw Wf, TM ! i > '~ uIsSe . : 9 M- ; eST8 * ------*H' us the usompaymg figure; nearly half the able workers bred ia the Greater London am, whereu the highest wneaunbcTB of rubber workers were in the Midlands d the North* West In the put there has beta a tmdaey mtutune that industrial bladder tumours concerned only diaidani ia the North of England; a study of the map ~ will show that this is not the case ' Kingdom, and only i tenth of the snout toed is the gam^ fsaure of ryn* and tube* i Cental Susttioi Otftee 1932). Aaboxidana ir manual upedieats in the n,-*| of rubber used Tor insulating or covering elesise aoles--<he same antin-rid inn (hot art used is the rubber industry. The as* withdrawn ia 1949 w-as popular is tOe cable industry, If we knew the numbers ud ages of all male workers agsged in the manufacture of elecaic ablrs during the same period, we could olculate ia rrperrsi number of bladder*rumour deaths to compare with our oiurvtd number of 63. Unfortunately this ia not possible beause the only sources of such information are the Reports of ad bed bets ia uae tiact 19)3, and possibly earlier. Tha tact ud in implications seta a live,neaped aouet foe e deads. Ism the possibility of a bladder-rumour (uord is the able fadussry sras metstioacd by tac British .liucjaoa of Urelogsal Surgeons (1941) and by Scoa .1962), and the oceurruee of deatha from bladder rumours aaon| able worfccn an* ooted by Case end Device (1943). Yet, only liter the publidty which tollowed the inquest on G. I_, a former able worker who died ia January, 1943(2-ise/r 1963a), was much anenbots paid to this ruk, sad it iceaj likely that in seventy abll sot fully Deaths Is Cable Workers the 1951 Census, and the occupation tables only a small group of tome 4SOO " Electric Cable ud Wire. Machine Drivers, Seners-up aad Assisana '* (coda 233,234); all other able-factory worken (number* Ing over 30,000) form part of heterogeneous groups of employees in the M Metal Manufacture, Engineering Allied Trsdcs la most cues the occupations given on the 65 doth . certificates indicate the able workers' satus(eg., labourer, cable maker, foreman) rather thaa the drptronma ia which they worked, and so aflord few dues is to whether The dsa analysed hat avert oburned by examining all the deceased men were in contact with tubba. We do, death carificatci on which papilloma or carcinoma of the however, know the histories of S of the men, ud all but bladder mu menboacd u a cause of death of males ia i of these had had centsa with rubber. It must b England aad Wales from 1943 to 1944. During these remembered that exposure cut occur without the actual 20 yean the occupation given oa 63 of these errufiata handling of rubber; this was illustrated in the cm of ''odicsted a worker ia the elecoic-able industry; ia the G. I_, whose recorded occupadoa of wire stranding was tasc period 1 IS such certificates related to rubber workers. . probably innocuous but who inarm'd inadcaal apoeure Table r gives the distribution of these deaths by date, aad when he visited the rubber departments in his factory in shows that in both industrial group the number of the course of fire-watching duties (Lancer 1945a). deaths haa increased in each ruecmsivt epnwgpj n-- The figure of 65 ia likely to be a eonsidtnble coder* admits of the number of men who worked is able factories ud subsequently developed bladder tumours, for it excludes three group of aea: - . (1) Those, such ts G. l_, who tare the industry and an nor doosbtd m their death cerafiates is able workers. Such cases do act usually come to light unless patients have been questioned about their put jobs and it ts possible to link ibeir aae-hiscoria with their death certificate*. (2) Those who develop blsider tumours but whose doth ccmfiotei do aoe mention this condition. Case tt iL (1934) (bund that 19', of patients with bladder rumours nooned by hospitals and known to be dead had no mention of this disease on their death certificates. (3) Those who have been successfully traced and in still living. At the Royal Mandcn Hospital alone eight such piocno have bem mated. Similarly the finite of tlB mutt be u understatement of the number of rumours among rubber workers, and there an be no d&ibt that the information nubble about the number of cases of industrial bladder tumour in the able and rubber industries is woefully inadequate. DfemifcuUaa W S>n4u Vy mur * mUM. Bladder Tumours as Cable Factary Attention waa fine drawn to these cases when a former worker sc a large ablc-fsctory m London was treated for tumour of the blsdJcr at the Royal Mirsdcn Hospital and reported that 2 of hia former workmate* had received similar treatment. The factory had recently been dosed down, but these 2 men were traced; it was found that they were alive and well, but had to the past been treated for papilloma of the bladder. All three men had worked in the rubber mill, and subsequently other asa from this department one to light. F,000617 jcir 24, Toe n* i ablet, tt 1949, am the ruhbcfeix vtn ftAQOAdl rabseque t^idscu aad the; deperme The i farmer a fist of teas tk That w- b^are If wkh the in the m Table o of the Li 10 Tars' Vale* sh occurred 1944-64. from nac differeoc to these already c tumour. Afi 6 more tha are given age of 60 the end > 4 dacha recurred No de: among t; However * 1-3 years and that group tor was in IS No coi G ^8 ADM 006<*<t7 WATER PCB-SD0000033968 TU* L-oxr pat 24. 1945 01I0IMAL AlTtCLIf thi Ljutcrr 1C ho.ro ia- workcn ttiit hi (heit ... Midlmdi n j tendency ^racd only of the.sap * ; rule - Juring th number of .-it obttretd .H because . Reporo of ,, Jitanguish Cable tad Assistants " (number* u* groups of p.acering tad ; the 65 death r.g., labourer, -jranena ia : to whether r-wT. Ve do, j. xad all but It must be the tetual : the ease of 'dins was . exposure hit factory ia I''65a). mble under* r'.-.-d ia eable flor rumours, *"T and ire ooe :rtm. Such r : have been t.; co link ther - whose death J. (1954) ' n nooffed by - this duuse . . ; 1 ; ' > . _ i i 1 I -: mj irt toll - : >och pacicaa . 'mneemeax ` Jrkers, and liable about ' -~-Our ia rhe u;vute. . a a former - treated for Iwtpiul and received Tn doted *J ihat they * * rrrated for - '`orlted ia k` *t from .Hi. f^ais u-t*as or tiani vro unotu or nram or uiu worn bUdde tumour among workers ia other departments oi mm this factory, but 6 eases have come co light, and three oi Tp* 1 ,Hn. lytVIMO If0>l3 teas**- <1 low 1 l ft. 1 Mr*. $ f 4 _ IT1 a 1^ -1 *% 4 u S-td jw >aw ! Ton >> i -1 it t s :' 2a4 s > IS a these patients hare died (ia 1959, 1964, and 1963). 2 o< the na eoeecTned were members of the scientific staff of tho firs 2nd ipcai font of tfitir ti^ic tt thii pvticuLu ficiw^ y, 1 man vaj a laborstonr technician; 1 worked on the process of mleaniuuoo, aad 2 worked in the stranding deparnaat. The first 1 ue believed ta have seraall. hsadled the annoxidant; the vuleaaiser ru presumably T*M u 1 J9 a JO ; iso exposed ta rapour from rubber compounded with this substance; the sennders may never have handled rub bo, The factory msaufacrured rabbcr-iasulated powa but it ia ka>M a that oat of there had ocmsioa co go iaco cables, sad used the tcttosdaai referred to from 1935 ta the rubba departmats, aad the other probably did 1949, sad posubly earlier. The operadoas earned out ia likewise. The period wha the anoosdant wia used the rubber mill included the weighing out of the additires included the whole of the 1939-45 war, aad it ia likely that were mixed with the raw rubber (these ioduded the that there was increased movement between deparaents antioxidant, ia powder form), the miting process, sad the at this time. Indeed, it would be difficult to delude subsequent rolliag of the rubber compound to i required exposure ia the case of aayoac who worked at this factory thidtaest. The coadas of the conductor wire with rubber during the war, for at oae sage the rubber mill served as aad the process of vulcanisation were carried oux ia other an air-raid shelter because it was on the grouad fleer of departments. one of the taongest buildings of the facary. The firm concerned pve access to the records of Pfiraerioa _- former workers at the factory, aad from these records a list of men said to have worked ia the rubber mill at tome time duriai the years 1935--19 was compiled. There were 139 such men excluding foremen end other M staff " workers. Many of them also worked ia the mill. before 1935 aad/or after 1949, but we are concerned oaly with the length of their exposure to the antioxidant, aad this length of exposure is deacd u the period of service in the mill berweta January, 1935, aad December, 1949. Table n shows the yevi of birth aad length of exposure of the 139 aiea; it aa be tea tbs 30 mm had ova 10 yesrT exposure. Examination of death certificates for Fngland cad The resula shown above strongly suggest that the risk of contracting occupational tumours of the bladda, already known m exist ia the rubba industry, into the dtrie<able industry. One of the ousal agoa a almost cenainiy an antioxidant of which manufacture ceased ia 1949, but w have do easuraaca that this a the only source cf daaga. The severity of the risk demonstrated ia oae group of rubba mill workers should help to dispel say doubt] abot*t the necessity fa tracing exposed workers sad offering them cytologies! saecaing tats. Than is a reason to suppose that the epidemic of rumours at this factory it unique, fa we know of dusters of 3 or mere Vales showed that 4 deaths from bladder tumoun had eases si some otha factories. It ia posaiblc that thorough occurred among the 139 mat during the 19-yea period torches would reveal macs at most cable aad rubba 1946*44. The expected cumber of such deaths, calculated factories that had used this annoxidant. Hitherto mow from national agc-ipecfic rates, was fouad to be 0-2. This factory managements have not been conscious of this rial difference it highly sigmficxat (PoO-OOOl). Ia sdditioa to their workers, and many cases of industrial bladda to these 4 deaths there art the two cases of pspilloma tumour hive gone unnoticed by them. No firm thoalc already meaaoned, --^"g a tool of 6 rases of bladder *-- that its workers have esaped this risk units. tumour. sautiny has bea made of the causa of doth of tl All 6 cases occurred among the group cf mm with present sad forma anployea who have died during th< more than 10 years' exposure, aad details of these cases past 10 or 20 years. Bladder-tumour is not a cemmoc ve given ia table in. All the deaths occurred uada the cause of death aad the number of narurally*oceurriai . age of 60 years. Thcrs are do grounds for believing that eases that may be expected to occur uada the iff o . the ad of this epidemic has been reached, for 3 of the 65 it very small; this it illustrsted by the cxpecuuoa o '. 4 deaths occurred last year, aad 1 of the 2 papillomas 0*2 deaths among the 139 mill workers ova s period o Nornd a few months ago. 19 years. ,x Sadtaths from bladder rumours have occurred to far. . * It scat inevitable that further cases of this disease wil (Mg the 109 men with shorts periods of exposure* occur as the result of past exposure, but it least we or Hewever, it should be noted that 25 out of the 35 men witlf hope that early diagnosis will save or prolong the lives o 1-5 years' exposure did not ater the mill uool after 1944, some of the future victims. and that rumours would be expected to develop ia this The probable industrial origin of many ates c group some 10 years late^ ihaa ia men whose first exposure bladda tumour among cable workers sppears to hav was ia 1935. j.* gone unnoticed not only by factory mmigaenis, bu Ko oomprehosivd torch has bea nude foe cases of alto by the doctors who treated theie oses. V hav ruu m--slaooc* tvmoiu ut iciici-wila waaxsas Tw*4 wi vwfc lA IA4 Twi*v*mwi A|9 ' mi in) r4-nfi*wi A0 4ia sff.) 42> s e hI144S:)>m2-A404 U'riumuw* im \m U'aiavw i~ * *- *4H4--14--- . 1. * ! 141) AA14ilf4fi*4" 1444 1444 ` . SJ . 44 1) noted that of 65 bladder-rumour deaths that occurrc amoog able workers some are def.nr.ely known to be c industrial oripn, and yet none of these 63 tr.ea wi certified as dying of industrial diseise. The most likel exp Ians non for this omission it that the desths were oc reported to coroners at being of pouible industrial ong*. because the cerufyiog doctors faiied to ponce this aspci tftop-Wdi--. l onnfi13 119 ADM 006*. WATER PCB-SD0000033969 U* jm.r K 1*45 ai-rtcm TX3 ULW3T As taforruaar* rerult of this Ud of mraai naoag docton is (hit la bust nuances when til* able workers vat netted to baefis far i p reuabcd industrial disexs* (am 39, pipiUoaoA'of Ibt'Ql^Jcr) nobody advised th* Bus that thiry vn Iflfcltt* far this bnrft, sad nnnrrn ary hardship **y hav* Suited; it is bettered that ha 1994 uadi and-TW oaiy *n* able wotta *u grentxd baric As old cues of mis iaduatiigj discus com* a light s number of daims pa beiaf mtd* retmpeesniy, tens by able- oartta- thou*free sad some by their widows (for mSuitrul widmn' pmiinniX To Inter ateat this lack of iwarcaea applies to euea at bladder tumour aanog rubber worsen, sad the deuth of research sad published iaformanoo ire largely rtrpoosibl* for this ignorance. Disquiet say be felt ora the tcceax response of the Medial Researdi Council had had more than 10 yean* exposurt o tfc* tnocsadm, md 6 of tboe men developed bladder taoun. So no wq observed among 109 mitt worken wuh short periods of exposure, but 6 forther i**Mn occurred imo^g wortors ia oth para of th foemry. Ia 7 of th* 12 aim th* diseas* proved fouL , There a no cerainry that all th* subtuaess responsible for thia risk hare been idaofied aad withdrawn; oaiy a foil investigation as ehiddate -*> point. , *4**^iv^akPr. t. E-TWipum Koaa director sft^ irfram td dotal revewea. aa* Mr. D. AL TaiUa. ----^ vU*SM.k*rtlMnn*a Ho,*ial.rascmuiinaaiaiavirvnuaa a* oi cm duual rvcardi; urru ,um unswpra lot is'armiuea tar sson; uw Qmiaai al a Urn esau-oasae Irm (or Va* ra*y mipii maa aa* tot prevndag dtmitd laorea; tod IS* ilnnry ol Libat* for ponding 2xa tOau mma M A--w (fjmen 1943b) to the request for aa independent - . fcirodpdoa into bladder tumoun in the rubber industry:, not oaly hss the Council declined to carry oux such tar- Jnrextigrooo ioeif, but it hss sunested that a more limited study of the iaddrnct of tusioun should be made by the Rubber Maauiscrunng Employee' Assodadoa--e body which opposed the publiadoa of the onpins! study of this problem, and which hss Dot published soy of the valuable informsboa is must possess from the first 7 yean* results of its cytologioi screening sernce. . Vaoat. TItn, dTtn(*IaWAB. tfutsniWa*X.nLanaMiaAt a I IHSi Uiwarol i^rmm (IM I) . J. Uni. 3X L laa,uan*Ar.wItaiT. la loannla Sim * MAoaai Aanai |mvo ISO* -- Dvnw. /. ()***> Sr. }. mo. tm. Mtd. tit *. -- Hmkm. M. L (ISM) **. a >. -- -- MrOaaaKD.S..FBnan.;.T.(lt4)aF liMtm.MM.ll.Tl. miamalnSaa,na|.no(lIM04Sn) sS(IufSutn)aAlnnSuiul oAaanianaAaat SSammuorar. dLt^MmMmmmm S'avtLMAO l: karwv an* Saalo; p. ML Ctpmdmm* a--wO(lMNfital ut s11o0*a. m . ` a. T. S. (If*l) Cimnpail aa* dtrnM TaAa Kao aC Aom* The basic reasoa why a thorough iaresbpboa of the ( rabbe (sad able) industries is sought remains the same aa when this was first proposed ia 1949: there it no. cataiaty that all the dangerous substances hare beca| Jdabfied and withdrawn from use. This doubt has bem strengthened by findiap such u the "^"""'""g rise ia EIGH-ALTTTUDE PULMONARY HYPERTENSION the number of certified deaths from bladder tumour ia able and rubber workers. 1 Iksoi Soma MJ. Piipiw. Fk-Chi, PJLCF.O, PJUdd. It has been seriously suggested that the naphthyiamiae OBMOTiMT 0< HBia* TO TB ASMS1 KtOM eoatcat of ctruia taboxidana may not hare bees the only dangerous coasts euea: of thes* produces. The eery high P. R. Kjunxa SLO. Poan* Masan Ltk MJ3.1 Incidence of bladder rumours ia one group of able waken leads some support to this suggestion, for bust mm wee in contact with ta antioxidant containing a mere 2'3% of tuphthyUmina of which oaiy >23'^ was the R. S. Hoom M.X. Paaiak, MJLCh-L B. D. P. Rao MJ3. forma, f.Cfuk, O.Cf. nomaea o* raraouoav fi-isome, so that their exposure to thes* caranogens m almost cmainJy much las sever* than that of groups of chemical workers with s similar rumour incidence. The impUatioa is that we may have to deal with a completely new and unsuspected class of chemical carcinogens. Gemmeset (1965) discusses th* fact that the survey of bladder tumoun among chrmioi vorken was made only long after the risk ia this industry had been first suspected, and comments **... it auy be difficult to future workers to andenand that to many oeodcs should pais before tabsbally sound evijuatioa of risk was earned out It seems ill.*o Italy that this remark may apply equally to any comprchaaahre study of th* rubber iadustry. From tAa Dirtamvu Cmurai, Armtd Form Mtdittl Smncm, . Stm DM, 11, IndU Rons ct aL (1936) fine reported that people living at high altitudes ia the Peruvian Andes had modente pul monary hypertension. It was less evidesx ia temporary residena with a year's continuous stay at high aibtude, and most evident ia patiena with chronic mountain sickness. Their findings ia permanent residents of th* Peruvian Andes wer* confirmed by Sime et aL (1963) and by Pefialozs ct aL (1963) and by findingi in the continental United Sara by Vogel ct aL (1962). ' hive been concerned mostly with hich-*Jtirude pulmonary hypertension in temporary residena in th* Himaliysa. Th* following is an account of our experience A high tnddcncs of blsdder rumours among shitted robber workers was demonstrated ia 1949 aad may has* been oased it least ia part by \n antioxidant used between 1923 and 1949. T^us high incidence has never been fully invesnga6. . Factories irunu/acrjnng electric power cables alto used bus antioxidant. Examination of death ccnifiaces for England and ^Fales for the yean 1943-64 revealed 63 cases of bLadder rumour where the deceased was of 102 cases. frtttspnlsi Factors Th* exposed population consisted of men |td between ll 104 47 yun For 93 temporary residents from ie*-l*vtl the rulntrsbU alrirudt begin it IldOO feet. For I person it * WOO feer, and for 2 persons born and broucht up >t in alimide of U J00 .ret the vulnerable altitude was IL500 feet and 14,400 fert I oun wsi s local rrtident livinf it 12.000 feet. In b| oca symptoms of pulmomry hipentnsion begin alter described as s able worker. 3ve to forty-rw-o months' suy at hijh jltitudt. In 1 men tlui la ooc large able factory 30 w orkers in the rubber mill bigh-aJurud* nay -u continuous for 6ve in in months, and in n-* V ra lu i:nno6i 9 120 ADH OOb'v WATER PCB-SD0000033970 jV-- ilif'ti .M.j, rf -i //*4 100U J roxxoLoerr aho utuao ntuMACoLouv J7, 456-MI (H70) - i (five ..>r l>ui : n 11 u ; If.ldiol 1 Comparative Toxicologic Study with Polychlorinated :..aie ' Biphenyls in Chickens v/iclt Special Reference to Porphyria, .... UMe 3 Edema Formation, Liver Necrosis, and Tissue Residues - .!!ilc 'i ,, ,hroc i J. C. Vos AH&p. H. Kocman : - k tr>- .*-.>>ruto i ImStUnt* / Yturitmry Pathebfy anti iha hutimta of Vtiartmry ihm-nm aiory W Taxie+icfj, Unntrutj / UtrrcJn, Utrecht, The StiAcrina -.pjratii |il 1 J, /Ml !h avers; >t Compamiv* Toxicologic Study with Polychlorinated Biphenyls in i Chickens with Special Reference to Porphyria, Edema Formation, Liver i Necrosis, and Tissue Residues. Vos, J. C. and Kooun, J. H. (1970). I he PC Toxin!. Appl. Pharmacol. 17. 656-66*. Tn a eomparitive 60-day oral toxicity test (400 ppm) in chickens, three 60*.{-ehlrinited commeeial polychlorineted biphenyl (PCB) preparations we used: eompound I *L*r l)P 6 until in t (Phenoclor OP 6). compound II (CTophen A60), and compound III (Arocior s kereU 1260). Using mortality, mean survival time, mean weight. and pathological j ,nniinu observations (hydropericardium, abdominal, and subcutaneous edema and they were eentrolobular liver necrotisl as parameters, a significant difference in toxi city was found between the compounds: compounds I and II showed the highest, compound III the lowest, toxicity. Microscopically eentrolobular liver necrosis was found in chicks fed compounds I and II. Atrophy of the . | he birds yiirepll.k.mtroL spleen was found in all lest groups. Chemical porphyria was found as a 1 lw> general PCB effect: increased fecal excretion of coproporphyrin and proto M'led ol a porphyrin ar.d fluorescence of tissues occurred in all lest groups. Additional , jreiuliy i experiments with compound I (2000 ppm) in Japanese quail and rats con firmed the porphyrogenic action. Gas chromatographic analyses of liver and brain ofdead chicks gave PCB levels thai varied between 120 and 2900 ppm. The relationship of hydropericardium (chick edema) ar.d liver mu* there jiul Die a group II i- necrosis to the differences in toxicity observed between the technical PCB h> the PC mixtures is diicutsed. - i!t warded In recent years the presence of polychlorinated biphenyls (PCB) has been exhibited in Ash and wildlife ip many countries, including the United States. Great Britain. Sweden, and Th Netherlands (Jensen, 1966; Holmes *l a!., 1967; Holden and Marsdcn, 19c*: Kocman n of., 1967; Risebrough et a/., 1965; KocmanerW.. 1969). NCommercial PCB preparations are oily fluids coosisdng of a mixture of different chlorinated biphcnjls. These chemicals are extremely.{table with very low aqueou* solubility. They arc used as lubricants, as fluids for heat transfer snd dielectric media, in protective coatings for wood, metal, and concrete, and for many other application* Which of these applieatiaps has contributed to the present widespread environment-!! At nevr r revile on removed f I the |W -n.l -utvi. liver. vple> ventuuial ..vjlm-vi*' !.hJ with r \Liun hit tontaminalion has not been elucidated. The occupational hazards in the use ol PI U ' have been known for years: normal handling of these compounds lias not given ri> to great difficulties (Irish, 196J). ' Animal experiments with rats and guinea pigs have shown that the ingestion of PCH vludiv-* 1 lluorv-en cweiivt ol . 656 IW0G20 121 aqm 00b*t .. ja-rxun WATER PCB-SD0000033971 klthough ipport it: at effect e magno- `OB thOM UUffl COft- r. 1967). agoesium -etion ob agsestum mt, which excretion a an augiaadmioiMio urine -hat aaiorthaad aad 3*1 SUppOCI j i : ! J magnesium ngttt u> rata. >. Root aad am metsbo- J. MnL rra. iemutry and -ynen. A. V. '4. Sficinger, - infmion on 1 m /' i laaq^oer om tmao huimacwjwt 19. <17-433 (1171) * Dermal Toxicity Studie* of Technical Polychlorinattd B(phnyla and Fractions Thereof in Rabbits J. C. Vos and R. B. Boms tetraw of Vttrriiarr fmkotefj W Inrinut tf KdrvirT rhrmmeoiory tid Ttxtrtbt/ {Jmtrrarj tf Utrrekt. Mtiwroot 172. Vend*. Jit Stthtrltmit ' KrrrietO OttoOtr S, 1979 Dermal Toaidty Studies of Techoieal Polychlorinsted Biphenyls and Fraction* Thereof in Rabbits. Vac J. G,, tod Bums. R. B. (1971). Toxin!. AffL tharmocoL 19.617-633. A significant differmct in toxiacy betwen 3 polychlorinated biphenyl (PCB) preparation* was found in a prior study: Gophea A 60 and Phcnodor DP6 showing the highest. Arador 1260 the lowest, toxidty (Vo* and Koeman. 1970), a subsequent study revealed the presence of tetra- and penuchJorodibenzofuran in Phcnodor and Clophen (Vo* ti oL, 1970). In the present study, applwation of 111 mf of the 3 PCI's (3 times per wk. for 31 days) on the bads skin of rabbiu also resulted ia difference* in toxidiy. FCB-tndueed skin lesions were hyperplasia and tryperkantoti* of the epidermal and follicular epithelium. Histopetholofy of the liver included centrelobular degeneration, ccmrclobuiar liver cell atrophy, focal necrosis, aad cytoplasmic hyalin degeneration. Definite hyperplasia and hyperkera tosis of the follicular cpithdium of the ear skin were seen after the topcal application of fractions of Phcnodor and Clophen eluted from chromato graphic columns with 23 % diethy lather in hexane. The fraction from Aro dor caused s minimal hyperplasia and hyperkeratosis of the follicular epithelium. PCB-induced 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 percentage of the diameter which corresponds to the space of Bowman. Moreover, thymus atrophy and lymphopenia were found. Fceal copro porphyria aad protoporphyrin excretion was increased Polychlorinated biphenyls (PCB) have been identified in tissues of fish and wildlife in many countries (Jensen. 1966: Holmes tt at.. 1967: Hoiden and Marsden. 1967; Koe- not..manera/_ 1967; Risebrough err/.. 1961; Koeman era/.. 1969; Jensen 1969; Duke of oi^ 1970: Frestt rr aA. 1970). ' PCS preparations arc extremely luble. oily fluids with very low aqueous solubility. They arc used as lubricants, as heat transfer media, in protective coatings for wood, metal, and toneme, and for many other applications. Which of these applications has contributed to the present cnvironmcntaPconumination has not yet been established. Inhalation and feeding experiments iri'rats with 63 chlorinated PCB resulted in liver injury (Drinker er al.. 1937; Bennett rr oL I93S). Liver damage and skin lesions have been described after inhalation, ingestion, and application to the skin using rabbits, guinea pigs, and mice (von Wedel rr oL. 1943). H>dropericardium occasionally accom panied by abdominal edema was found in chicks fed PCB (VtcCune rr ol,, 1962. Flick 617 F000621 122 A0H 006** 51 WATER PCB-SD0000033972