Document 15BkGoaMxzM0azvp5d9EaD78a

Human Health effects of electrical-Grade PCD s GENP 002020 Corporate Health & Safety Operation GENERAL ELECTRIC PLAINTIFF'S EXHIBIT >371 736770 HUMAN HEALTH EFFECTS OF ELECTRICAL-GRADE PCB's J.F . Brown, J r ., Ph.D. Manager - Life Sciences Branch Corporate Research and Development C enter Schenectady, N .Y . J .T . Coe S ta ff Executive Environmental Q uality & Safety Corporate Health & Safety Operation F airfield, Conn. H .D . Pocock, J r ., M.D. Associate Company Medical D ire c to r ( r e tir e d ) Corporate Health & Safety Operation Fairfield, Conn. Corporate Health & Safety Operation General Electric Company 3135 Easton T u rn p ik e F a irfie ld , Conn. 06431 A u g u s t, 1981 GENP 002021 73677t "it.1 *m ain jii-iiiw 1 INDEX Page Section Section Section Section I Introduction II PCB Composition and Term inology 111 H is to ry o f PCB Use IV Health Effects o f PCB and PCDF M ixtu res 2 4 7 9 A. Observations on Test Animals 1. General Bioeffects 2. Im p u rity Effects 3. S tru c tu re -A c tiv ity Relationships 4. T o x ic ity and C arcinogenicity Test Results B. Human Health E ffects O bservations 1. E arly Occupational Chloracne 2. Yusho Episode 3. Effects o f Eating Fish C ontaining PCB's 4. Clinical Studies of Capacitor Workers 5. NIOSH M o rta lity S tudy 11 C. Health Effects Summary 18 Section Section Section V U. S. PCB R egulations VI On'-going Research Programs 'VII References Cited 20 22 23 A b b re v ia tio n s w hich may be u n fam iliar to some readers in clu d e : ppm p a rts p e r m illion ppb parts per billion kg kilogram ; 1000 grams gm gram (s ) mg m illig ra m (s ); one thousandth of a gram pg/m3 micrograms (m illionths of a gram ) per cubic meter p g /L micrograms per lite r (a p pro x. = ppb) LD50 an acute to x ic ity measurement meaning dose lethal fo r 50% o f th e test animals EPA Environm ental Protection Agency FDA Food and D rug A d m in istra tio n GGTP L iv e r serum enzyme gamma glutam yl tra n sp e p tid a se HEW Health, Education and Welfare Department (now called Health and Human Resources D epartm ent) NIOSH National In s titu te fo r O ccupational S afety and Health OSHA Occupational Safety and Health A dm inistration p ,p ` -DDE M etabolite o f DDT p re sen t as backgro u n d in blood analyses SGOT L iv e r serum enzyme glutam ic oxaloacetic tra n sa minase TLV T h re s h o ld L im it Value: an exposure concentration representing conditions under which it is be lieved th a t nearly all w orkers may be repeatedly exposed day after day w ithout adverse effect. -1- 736772 Human Health Effects of Electrical-Grade PCB's* Section I __________ Introduction Although the production of polychlorinated biphenyls (P C B 's) in the U .S . has been banned, d e fin itio n o f th e human health ris k s th e y may pose continues to be an im p o rta n t issue. The PCB's were w id e ly used fo r n e a rly 50 ye a rs, c h ie fly as d ie le c tric flu id s and p la s tic iz e rs , and large amounts are s till present in electrical equipment th a t w ill re q uire servicing and disposal. PCB's are also p re sen t in numerous environm ents th a t may, o r may n o t, m erit containment o r restorative actions. Small, b u t measureabie levels are found in some edible fis h . T h u s , the potential fo r human exposure to PCB's remains. A t p re sen t, Company managers, employees, physicians and public officia ls concerned w ith appropriate handling of these exposure situations face a c o n tra d ic to ry a rra y o f inform ation on the possible health hazards. On the one hand, the U. S. press and environm ental lite ra tu re ( e . g . , re f. 1) in c re a s in g ly p o rtra y PCB's as v e ry to x ic m aterials, and situ a tio n s re s u ltin g in human exposure at any level as hazardous and a larm ing. The T o x ic Substances C ontrol A c t of 1976 (TS C A ) and a tte n d a n t re g ula tio ns g e n e ra lly ban PCB m anufacture, processing and d is trib u tio n ; se ve rely lim it use; and impose s tr ic t requirem ents fo r PCB lab e lin g , disposal and storage fo r disposal. On th e o th e r hand, many European countries have made a q u ite d iffe re n t ris k /b e n e fit assessment o f PCB's since th e y continue to perm it PCB m anufacture and use in closed e le ctrica l equipm ent. More im p o rta n tly , 40 years o f U .S . occupational exposure in capacitor m a n ufactu rin g has p roven re la tiv e ly u n e v e n tfu l, as judged by documented adverse health e ffe c ts . Many medical studies o r observations o f human populations th a t were heavily exposed to PCB's have been reported (2 ,3 ,4 ,5 ,6 ,7 ,8 ,9 ,1 0 ,1 1 ,1 2 ,1 3 , 1 4 ,1 5 ,1 6 ,1 7 ,1 8 ,1 9 ,2 0 ,3 3 ,4 7 ,4 9 ,5 0 ,5 1 ,5 2 ,5 5 ,5 6 ,5 9 ,6 0 ,6 1 ,6 3 ). Some o f these in v e s tig a tio n s are v e ry re ce nt and have only become available since the p u b lic image o f PCB's was form ed. Not all are y e t re p orted in th e p u b lished lite ra tu re . The authors have undertaken th is paper to provide perspective fo r General Electric managers and physicians, and to help id e n tify situations o f human exposure to PCB's th a t m ight present cause fo r co n cern . I t draws on e xte n sive GE experience in pla n ts m an ufactu rin g P C B -fille d ca p acito rs, as well as on review o f the s c ie n tific lite ra tu re . The paper reflects today's knowledge and may be extended i f s ig n ific a n t new inform ation becomes a vailable. The concluding section describes o n -g o in g research th a t may p ro v id e additional inform ation re le v a n t to some present uncertainties. This paper presents many quantitative observations because these are c ritic a lly im po rta n t to any health effects perspective. The fa c t th a t PCB's are p e rs is te n t and. re a d ily detectable at low concentrations does n o t neces s a rily mean th a t th e y are to xicological ly s ig n ific a n t. *4s used throughout this paper "electrical-grade PCB's" describes various PCB's used in GE capacitors and transformers. -2- 736773 GENP 002023 Section I Introduction The PCB b io e ffe cts lite ra tu re is volum inous, com prising several h u n dred o rig in a l a rtic le s . The present paper w ill not attem pt to su rv e y all aspects o f th is inform ation, b u t w ill focus on those portions the authors judge most re levant to human health effects evaluation. In addition to lite ra tu re citations the bibliography lists health-related conference reports (21,22,23,24,25) and several review books and documents (26,27,28,29,30). GENP UU2024 rt I -3- 736774 Section II PCB Composition and Terminology In chemical term inology "p h e n y l" denotes a rin g s tru c tu re of six carbon atoms attached to something else; "b ip h e n y l" re su lts when two such rin g s are attached to each o th e r; and a "po lych lo rina ted b iphenyl" (PCB) is any molecule having m u ltip le c h lo rin e atoms attached to the carbon atoms of a biphenyl nucleus. Biphenyl and a representative trichlorobiphenyl. (PCB) are illu s tra te d below: Cl B ip h e n y l 2 ,4 ,4 ,-T richlorobiphenyl (a PCB) T h e re are 209 th e o re tic a lly possible ch lo rin a te d b ip h e n yl molecules, d iffe rin g in the numbers (homologs) and positions (isom ers) o f the attached c h lo rin e s ; o f these 209 species, about h a lf have been id e n tifie d as being p re se n t among the complex m ix tu re s th a t c o n s titu te commercial PCB p ro ducts. These products range from lig h t o ily flu id s (d i- , t r i- , and te tra chlorobiphenyls) to heavy, honey-like oils (penta-chlorobiphenyls) to greases and waxes (more h ig h ly ch lo rin a te d ). The m anufacturers of PCB's sold them under tra d e names; e .g ., "A roclor" (Monsanto, USA), "Phenoclor" and "Pyralene" (Prodelec S .A ., France), "Clophen" (Farbenfabriken Bayer AG, Germany), or "Kanechlor" (K anegafuchi Chemical In d u s tria l Co. L td ., Ja p an ). T h e y also assigned product numbers th a t usually reflected either the average degree of ch lo r ination o r, what is equivalent, the w e ig h t-p e rce n t chlorine in the m ixtu re. T h u s, the American A roclor 1242, its French equivalent, Phenoclor DP3, and its Japanese e q u iv a le n t, Kanechlor 300, all contained 42% c h lo rin e , o r 3 c h lo rin e atoms p e r b iphenyl on th e average. Likew ise, A ro c lo r 1254 and its German e q u iv a le n t, Clophen A50, contained 54% c h lo rin e , or 5 ch lo rin e atoms per b ip h e n y l on the average. A ro c lo r 1016 designated a Monsanto PCB p ro d u c t sim ila r to A ro c lo r 1242 w ith enhanced b io d e g ra d a b ility , w hich was accomplished b y removal o f h ig h e r ch lo rin a te d homologs. Electrical equipment m anufacturers fu r th e r p u rifie d these commercial PCB p ro d u c ts to in s u re e le ctrica l perform ance; blended them w ith s ta b i lize rs and d ilu e n ts ; and then p u t th e re s u lta n t PCB m ixtu re s into capaci to rs and tra n s fo rm e rs u n d e r th e ir own tra d e names and p ro d u c t num bers. GE's tra d e name fo r its PCB m ix tu re s was "P y ra n o l." "A s k a re l" is a gen e ric , in d u s try -w id e term fo r a PCB o r o th e r fire -re s is ta n t d ie le ctric flu id . 4- 736775 GENP 002025 Section II PCB Composition and Terminology In s h o rt, the m aterials now c o lle c tiv e ly re fe rre d to as "P C B 's11 are d iffe re n t complex m ixtures of chlorinated biphenyls used u n de r a v a rie ty of p ro d u ct nam es.. These m ixtures always contained several dozen in d iv id ual PCB isomers and homologs clu ste re d around some average degree o f c h lo rin a tio n , fre q u e n tly some trich lorobenzenes as d ilu e n ts ; o fte n about 0.5% o f an a lip h a tic epoxide as a s ta b iliz e r; and p a rts -p e r-m illio n levels o f tra ce im pu ritie s such as the p o ly ch lo rin a te d d e riv a tiv e s o f m e th y lb ip h e n y ls , te rp h e n yls, naphthalene or dibenzofuran. R eturning to chemical te rm ino lo gy, " fu ra n " denotes a rin g s tru c tu re of fo u r carbon atoms and one oxygen atom; and " d ib e n z o fu ra n " a tr ic y c lic arrangem ent of two benzene ring s and one fu ra n rin g fused to g e th e r. T h is s tru c tu re can re s u lt i f an oxygen atom is added to a b ip h e n y l system . If m u ltip le c h lo rin e atoms are attached to th is n u cleus, then a " p o ly c h lo r inated d ib e n z o fu ra n " , o r PCDF, re su lts as illu s tra te d below. T here are 135 th e o re tic a lly possible c h lo rin a te d d ib e n zo fu ra n s. O 1,3,7-T richlorodibenzofuran (a PCDF) T race levels o f PCDF's have been detected in la b o ra to ry samples o f U. S. PCB's, including specimens o f both in d iv id u a lly synthesized isomers and commercial m ixtures (3 2 ,3 7 ). There are two plausible explanations fo r the presence o f PCDF's in commercial PCB's: F irs t, contam ination may have o ccu rre d d u rin g m a nufacture, possibly as a re s u lt o f o xyg en in th e benzene used to make the o rig in a l b ip h e n yl. Such contam ination may have existed in French and Japanese PCB's, b u t a p pa re n tly was n ot s ig n ific a n t ly present in American-made PCB's a fte r one episode in 1933. Second, PCDF's may have been form ed d u rin g usage as a re s u lt o f h ig h tem pera tu re o xid a tio n . O xidation experim ents (31) re p o rt maximum conversion of A ro c lo r 1254 to to ta l PCDF's as 2-3% at 550-600C. C onditions su ita b le fo r s ig n ific a n t conversion o f PCB's to PCDF's did not e x is t in th e normal m anufacture o f, and are not expected in the normal use o f, capacitors and tra n sfo rm e rs, b u t may occur in high-tem perature heat exchangers. 736776 - 5- 930' Section II PCB Composition and Terminology A related group of molecular species mentioned in th is paper are the polychlorinated quaterphenyls (P C Q 's), which contain fo u r phenyl units and a v a ria b le num ber o f ch lo rin e atoms as illu s tra te d below: -6- 736777 GENP 002027 Section III History of PCB Use The Swann Chemical Co. began commercial U .S. production o f PCB's in 1929. In 1935 Monsanto In d u s tria l Chemicals Co. (M onsanto) purchased Swann and continued the m anufacture of PCB's, in itia lly at A nniston, Ala. and later at Sauget, III. PCB's are excellent non-flammable, h ig h -b o ilin g , therm ally and chemi ca lly stable d ie le c tric s and so lve n ts, and these p ro p e rtie s led to a w ide range o f in d u s tria l a p p lica tio n s. In a d d itio n to s e rv in g as d ie le c tric flu id s in capacitors and tra n s fo rm e rs , PCB's were used as p la s tic iz e rs , h y d ra u lic and heat exchange flu id s , and were inco rporated into such p ro du cts as d u st-se ttlin g agents, die-casting lub rica nts, inks, dyes, paints, pesticides and adhesives. PCB's were w idely used in carbonless reproduction paper and entered paperboard production. PCB's from such sources have entered into the environm ent. Slow b io d e g ra d a b ility and bioaccumulation account fo r the presence of PCB's in Sediments under riv e rs and lakes and in fis h . Trace quantities have been found in some o th e r food as w ell. As a re s u lt, PCB's are found in tra ce qu an titie s in the blood and fa tty tissue of the human populations o f all industrial nations. Concern o ve r such accum ulations in th e environm ent led Monsanto in 1970 to begin v o lu n ta rily re s tric tin g PCB sales to m anufacturers o f sealed e le ctrica l equipm ent (3 3 ). In 1976 Congress enacted TSCA, w hich man dated a phaseout o f PCB p ro d u ctio n and use. A lth o ug h sim ilar PCB phase outs were in s titu te d in Japan, Canada and Sweden, many other in d u stria l nations ( e . g . , U .K ., Germany, France, Spain and o thers) continue to pe rm it PCB production and the m anufacture of P C B -filled capacitors and transform ers. Estimates (34) fo r the cum ulative total of U .S. PCB's from 1930 to 1975 and th e ir se rvice status in Table 1 below: Table I ind u stria l uses 1976 are noted of in Use C a p a cito rs T ransformers P la s tic iz e rs H ydraulics and Lubricants Carbonless copy paper Misc. in d u stria l Heat tra n s fe r Total M illions of Pounds In d u s tria l PCB's C u rre n tly PCB Purchases in Service. 630 450 335 300 T115 i 80 45 8 28 I 20 T 1253 758 -7 - 736778 GENP 002029 Section 111 History of PCB Use Estimates (34) of the status of these PCB's are shown in Table II below: Table II D is p o sitio n Environm entally biodegraded Incinerated Landfills and dumps In soil, w ater, a ir and sediment C u rre n tly in electrical service In use other than electrical service Total _ M illions o f Pounds 30 25 290 150 750 8 1253 GENP. >2030 736779 - 8- Section IV Health Effects of PCB and PCDF Mixtures A. Observations on Test Animals 1. General Bioeffects PCB's resemble other fa t-s o iu b le chlorinated o rg a n ic chemicals in biological uptake and in te rn a l tr a n s p o r t. An animal can re a d ily absorb PCB's th ro u g h the lungs upon inhalation o r th ro u g h the intestines follow ing in g e stio n , o r less re adily th ro u gh th e skin a fte r p h ys ical contact. Fish can absorb PCB's th ro u g h the food chain o r th ro u g h th e ir g ills , and th e bioconcentration fa c to rs * can range between 103 and 106. Once inside th e body PCB's g ra d u a lly d is trib u te themselves equally among all fa tty deposits p re se n t. Elimination processes are g e n e ra lly slow, especially fo r the more h ig h ly chlorinated homofogs. When increasing doses o f PCB's are adm inistered to animals the f i r s t observable e ffe ct is the in d u ctio n , p rim a rily in the liv e r, o f the ce llu lar enzymes v a rio u s ly known as "d ru g m etabolizing" o r "d e to x ific a tio n " en zymes, o r as "m ixed fu n c tio n " ( i . e . , chem ically n o n -s p e c ific ) oxidases. These enzymes catalyze chemical processes by which th e animal's body seeks to co n ve rt lip id -s o lu b le fo re ig n chemicals into w a te r-so lu b le sub stances excretable in the u rin e . Such effects are also produced by many o th e r substances, and are g e n e ra lly regarded as physiological ra th e r than pathological processes. A t high enough doses in anim als, PCB's can induce many typ e s o f to xic effects and eventually death. The reported toxic effects w ith chronic exposure include c h ic k edema disease and teratogenesis in ch icke n s; liv e r h y p e rtro p h y , fib ro s is , neoplasia and cancer in rodents; g a s tric and d e r matological lesions in monkeys; and rep ro d u ctive d ysfu n ctio n in several species. An extensive lite ra tu re on th is subject is referenced in the bibliography (21-30). T h e re can be d iffe re n c e s in to x ic ity between d iffe r e n t PCB p ro d u c ts , w ith the h ig h e r homologs generally being reported more to x ic in chronic tests and th e lower homologs more to x ic in acute te sts. T here can also be larg e to x ic ity d iffe re n ce s observed between d iffe re n t specimens o f the same type o f PCB, apparently caused by im purity-level variations. 2. Im purity Effects In 1970 a Dutch s c ie n tis t, J .G . Vos, ob served s trik in g differences in ch ick em bryotoxicity among th re e commercial PCB's th a t all contained 60% c h lo rin e : A ro c lo r 1260 (w hich had v ir tu a lly no e ffe c t), Clophen A60, and Phenoclor DP6. He then dem onstrated th a t the v a ria b le to x ic agent in th e system was an im p u rity , p o ly c h lo rin a te d d ib e n - zo fu ra n (PCDF) (3 5 ). He also showed th a t th is im p u rity was responsible fo r chloracne in PCB dermal te s ts w ith ra b b its (3 6 ). I t is not possible to determ ine if the to xic response v a ria b ilitie s ob served in o th e r PCB animal te s ts should be ascribed to v a ria tio n s in PCDF levels because, u n fo rtu n a te ly, few of the investigators reported im p u rity levels in th e PCB specimens th e y te s te d . Chemical analyses have su b - 'A bioconcentration factor is defined as the ratio of the PCB concentration in a fish to that in its ambient water. - 9- 736780 GENP 002031 I Section IV Health Effects of PCB and PCDF Mixtures se q ue n tly re p orted th a t European and Japanese PCB's contained 5-20 ppm PCDF as m a n ufactu red , w hile the U .S .-m ade A ro clo rs had 0-2 ppm (3 7 ). 3. S tru c tu re -A c tiv ity Relationships Many recent animal .studies have aimed at re la tin g the molecular s tru c tu re s o f in d iv id u a l PCB, PCDF or" sim ilar molecules to th e ir biological a c tiv itie s . These studies have shown th a t chloracnegenic a c tiv ity is spe cifica lly associated w ith molecules shaped like fla t rectangles with chlorines at the corners (32). All such chloracne genic species are also capable o f ind u cing one specific ty p e o f mixed fu n c tio n oxidase, designated cytochrom e P448 because o f its sp e ctra l ab sorption band position. Most lower homolog PCB molecules do not induce P448; how ever, some h ig h e r c h lo rin a te d PCB homologs, w hich c o n s titu te a few p e rc e n t o f th e h ig h e r A roclors and which are v irtu a lly absent from the lower A ro clo rs, do e x h ib it moderate P448-inducing a c tiv ity . By comparison, 2 ,3 ,7 ,8 -te tra ch lo ro d ib e n z o fu ra n is 700 times as p o te n t a P448 in d u c e r in ra ts as th e a ctive PCB isomers and is many o rd e rs o f m agnitude more b io lo g ica lly p o te n t than most o th e r PCB and PCDF molecules (26 chap. 6 ). 4. T o x ic ity and C arcinogenicity T est Results T o x ic ity te stin g of PCB's in experim ental animals has produced a large body o f experim ental observations. Repeated sh o rt-te rm feeding tests have shown th e acute to x ic itie s o f PCB's in animals to be low , w ith LDS0 values re p o rte d from 1,300 to 11,300 mg per kg of body w e ig h t (2 9 ). Concerns over chronic human health effects o f chlorinated aromatic hydrocarbons (in c lu d in g PCB's) led to a series o f 3-4 month inhalation te sts in animals at the H arva rd School of P ublic Health in th e 1930's (38) and confirm atory tests at the U nive rsity of C incinnati's K ettering Labora to r y in th e 1950's (3 9 ). From the o b serva tio n s in both te s t series th e in v e s tig a to rs recommended th re s h o ld lim it values (T L V 's ) o f 1000 pg/m 3 fo r PCB's w ith 42% c h lo rin e o r less, and 500 pg/m 3 fo r th e more h ig h ly c h lo r inated PCB m ix tu re s . These T L V 's , used b y in d u s try d u rin g th e remain ing period o f PCB use, were accepted as sta ndards by th e Am erican Con ference of Governmental In d u stria l H ygienists (ACG IH) in 1956, and by OSHA in 1971, and were adopted b y many o th e r countries as w ell. When PCB's are ch ro n ica lly adm inistered to ra ts in increasing doses, th e re is a p pa re n tly a dose-related progression from "n o -e ffe c t", to m ild, re ve rsib le effects (40) to serious irre v e rs ib le liv e r disease. The observed progression o f effects on rodent liv e rs includes ce llu lar enzyme in d u ctio n , microsomal p ro life ra tio n , cellular h y p e rtro p h y , focal necrosis, fib ro s is and eventually the development of increasingly abnormal types of tissue (41,42, 4 3 ). In some o f these te sts in ro d e n ts , PCB's have been judged to show ca rcin o g e nic a c tiv ity , w hile in o th e r te s ts th e same m aterials (A ro c lo r 1254 and 1260) were judged not to have shown carcinogenic a c tiv ity (33, 42,43, 44) . -IQ - 736781 t GENP 0U2032 Section IV Health Effects of PCB and PCDF Mixtures Reports o f positive carcinogenic fin d in g s in long-term tests of sub stances in rodents at high dosage levels, while prom pting caution w ith re sp ect to human exposure, are not an uncommon o b se rva tio n . General E le c tric has noted th a t in HEW's "S u rv e y of Compounds Which Have Been Tested fo r C arcinogenic A c tiv ity " , PHS Document 149, Vols, 4 ,5 ,6 , & 7, 70% to 80% o f all substances tested from 1960 to 1973 were reportad to produce excess tum ors in animals (4 5 ,4 6 ). B. Human Health Effects O bservations 1. Early Occupational Chloracns Reports D uring the fir s t years th a t PCB's were in in d u s tria l use, th re e Am erican medical re p o rts described unambiguous episodes o f P C B -linked occupational illn e s s .* Two invo lve d PCB vapors from h ig h -te m p e ra tu re equipm ent, and the o th e r was ascribed to an u n id e n tifie d im p u rity . 35 The f i r s t episode occu rre d in 1933 a t the Swann Chemical Co. when 23 o f 24 men w o rk in g on th e m anufacture o f PCB's almost sim ultaneously developed skin e ru p tio n s diagnosed as "c h lo ra c n e ." The e ru p tio n s were sim ilar to adolescent acne, i.e ., a progression of blackheads and pustules th a t pe rsisted several months before d isa p p e a rin g . Some of the men also complained of lassitude b u t showed no clinical signs o f ill health other than th e s k in co n d itio n . In th e ir re p o rt on th is PCB episode, the in v e s tig a to rs concluded th a t th e to x ic agent was p ro b a b ly an u n id e n tifie d im p u rity th a t appeared in th e PCB when a new source o f c ru d e benzene was used fo r m aking the b ip h e n yl (4 7 ). When purchase from th is benzene source was discontinued and the process equipment b e tte r enclosed, the problem disappeared. C hloracne was known by th is time to be induced b y ch lorinated coal ta r products and by chlorinated naphthalenes (Halowaxes). Later, occupa tio n al chloracne was fre q u e n tly observed among e le ctrica l w orkers who handled "cable w ax" containing th e la tte r m aterials. Chloracne was found to clea r up some time a fte r the contact was removed and im proved hygiene in s titu te d . Concerns about long-term effects o f chloracne have been ad dressed b y a re ce n t s tu d y , in w hich a g ro u p o f 121 male chemical w o rke rs who had experienced a chloracne a tta ck in 1949 (u n re la te d to PC B's) showed no excess in to ta l m o rta lity nor in cancer m o rta lity a fte r 29 years (4 8 ). A background incidence o f chloracne in children in N orthern Ita ly has been re p o rte d as 0.1-0.5% (26, p .3 3 1 ). T he second episode in v o lv in g PCB's o ccu rre d in 1950 and 1951, when 7 o f 14 people exposed to vapors (re p o rte d a t, 100 pg/m 3) from a leaky PC B-containing heat exchanger developed chloracne (4 9 ). A th ird epi sode was noted in th e e a rly 1960's when 13 o f 16 people exposed to vapors from an oven in which PC B-plasticized enamels were being baked were sim ilarly affected (50). 'Some other early papers confusingly associated PCB's with the health effects of certain other chlorinated hydrocarbons._____ ____ - 11- 736782 GENP 002033 Section IV Health Effects of PCB and PCDF Mixtures 2. Yusho Episode Despite the long and re la tiv e ly uneventful PCB occupational exposure experience the Japanese "Y u sh o " (o il-d is e a se ) in c id e n t in 1968 created a wave o f concern. In th a t episode some 1300 people in southwestern Japan developed a v e ry severe and p e rsiste n t form of chloracne a fte r eating rice oil found to have been contaminated by flu id leakage from a heat exchanger o rig in a lly fille d w ith Kanechlor 400, a Japanese PCB ( 5 1 ) .* In addition to the acne-like eruptions and feelings o f lassitude p re v io u s ly observed in chloracne outbreaks, the Yusho victim s commonly ex hibited swelling of the upper eyelids, increased eye discharge, h yp e rpigm entation of the nails and s k in , sweating o f th e palms and a v a rie ty of o th e r in d ivid u a l e ffe cts. Signs o f th e disease were also tra n sm itte d in some cases to newborn c h ild re n . The brown dermal pigm entation o f these c h ild re n is re p orted to have dim inished w ith tim e. (26 chap. 9 B 1 ). In th e same period a ch ic k edema epidemic th a t kille d 400,000 chickens was traced to consum ption o f feed con ta in in g the same rice o il. The f i r s t contam inant to be id e n tifie d in th e ric e oil was Kanechlor, and a w idespread demand fo r controls o r elim ination o f all PCB's re su lted . A fte r th e Vos id e n tific a tio n of PCDF im p u ritie s as th e a ctive to x ic a gent in two PCB animal te s t sytem s, Japanese s c ie n tis ts reanalyzed some o f th e rice oil specimens th a t had caused Yusho illn e ss (5 2 ). From 1975 to 1978 i t became known th a t these rice oil samples contained a bout 1000 ppm PC B's, 5 ppm PCDF's and 1000 ppm o f another ch lo rin a te d m a te ria l, la te r id e n tifie d as p o ly c h lo rin a te d q u a te rp h e n yl (5 2 ,5 3 ,5 4 ). The PCDF's and PCQ's presum ably were form ed from PCB's b y therm al o xid a tio n and con densation in th e heat exchanger at high tem perature. The appa re n t PCDF content of the leaking heat exchanger flu id , calculated from the above analysis o f rice oil contam inants, is 2500 ppm (0.25% ), a v e r y high level compared to PCDF levels in U .S . e le c tric a l-g ra d e PCB's as m anufactured (0-2 ppm). As the Yusho victim s were estimated to have ingested an average of 2.0 gm o f the heat exchanger flu id (5 1 ), th is amount would have included about 1.0 gm each o f PCB and PCQ, along w ith a p p ro xim a te ly 5 mg of PCDF. As w ill be noted la te r, 1.0 gm o f PCB is less th a n th e average body burden of heavily exposed capacitor w orkers; however, the Yusho victim s a p p a re n tly elim inated th e ir PCB burdens more ra p id ly th a n capaci to r w o rke rs, e x h ib itin g nearly normal background levels o f PCB's a fte r 5 years. Nonetheless, many Yusho patients remained s ic k , and such autopsy liv e r samples as became available showed co n cen tra tio n o f p e nta - and hexa-chlorinated PCDF's in th a t organ (5 2 ). 'A second episode, involving essentially identical circumstances and consequences, has just teen reported from Taiwan (59). GENP 002034 736783 -12- Section IV Health Effects of PCB and PCDF Mixtures These la te r Japanese in v e s tig a tio n s lin ke d th e disease to th e PCDF c o n te n t of th e rice o il. T h is conclusion is co n sisten t w ith PCDF a c tiv ity in animal tests and w ith th e observation th a t body burdens of e le ctrica l-g ra d e PCB's (fro m inhalation and skin c o n ta c t) la rg e r than the PCB doses in gested by Yusho victim s have not induced Yusho illness in capacitor w o rke rs. The Japanese Yusho in ve stig a to rs also re p orted th a t th e minimum dose fo r in d u c tio n o f th e disease was about 0.5 gm o f th e th e rm a lly decomposed heat exchange flu id (th e PCB-PCQ-PCDF m ixtu re ) (5 1 ). Using a range of re p o rte d PCDF analyses (5 2 ), th e PCDF to x ic ity th re sh o ld dose m ight th e re fo re be estimated at 1.0' - 1.5 m g ,* A sim ilar threshold dose (1.26 mg) has been estimated from data on th e amount o f PCDF consumed b y pa tie n ts before the onset of the symptoms in the recent episode in Taiwan (60). 3. Effects of Eating Fish C ontaining PCB's The Michigan De partm ent of Public Health, under the sponsorship of FDA, conducted a s tu d y o f 182 a d u lts , 105 of whom consumed over 26 pounds o f G reat Lakes fis h p e r y e a r. A s ig n ific a n t c o rre la tio n between blood PCB levels and q u a n tity o f fis h eaten was o b serve d . The mean blood PCB value fo r th e exposed g ro u p was 73 p p b , w hile th a t o f the comparison g ro u p was 20 p p b . In d iv id u a l blood PCB levels ranged from 7 ppb fo r a person who ate no fis h to 366 ppb fo r one who ate 132 pounds p e r ye a r (1 1 ,1 2 ). Evaluation o f health h isto rie s and c u rre n t medical problems of the s tu d y subjects failed to id e n tify a sig n ific a n t difference between the ex posed and comparison g ro u p s . Symptoms c h a ra c te ris tic of re p orted PCB to x ic ity (Yusho symptoms) were not found nor did those w ith the highest PCB levels have a co n sisten t p a tte rn o f com plaints o r co n d itio n s. A lth o u g h th e data dem onstrate an association between fis h consumption and PCB levels in humans, no to xic manifestations from th is exposure have been id e n tifie d to date (1 2 ). The question of . PCB accumulation over time and the effects of long-term exposure are being evaluated in a continuation of this study. A re ce nt s tu d y (61) o f 458 persons who had s ig n ific a n t exposure to DDT from eating fis h also re p o rte d PCB blood levels (a rith m e tic mean, 22 p g /L ; range 3.2 to 158 p g /L ) . T he a u th o rs re p o rt th a t th e fo llo w in g s ig n ific a n t correlates o f log diastolic blood pressure m ight account fo r 24.1% o f its v a ria tio n in th is c o h o rt: body mass in d e x , 6.8%; sex, 8.3%; log PCB le ve l, 6.3%; age, 1.5%; H ollingshead in d e x , 1.1%. 4. Clinical Studies of Capacitor Workers The most extensive long term exposure o f humans to PCB's has probably occurred in capacitor p lants around th e w o rld . (T h e re w ere 17 ca p acito r plants using PCB's in *A recent reanalysis of YUSHO patient data puts this figure at 0.6 mg. (26 p. 291). GENP 002035 - 13- 736784 Section IV Health Effects of PCB and PCDF Mixtures the U .S .) Many employees in these plants had d a ily PCB skin contact fo r several years and inhaled PCB's at levels in the 100 to 1000 pg/m 3 range. General E le c tric 's major capacitor flu id usage was o rig in a lly A ro c lo r 1254, th e n changed to A ro c lo r 1242 around 1954, and s u b se q u e n tly to A ro clo r 1016 (and some 1221) in 1971. T h is usage p a tte rn was p ro b a b ly ty p ic a l o f the in d u s try . PCB blood te sts o f 174 h e avily exposed GE ca p acito r w o rke rs have ind ica te d a geom etric mean* around 300 ppb and an a rith m e tic mean o f about 500 p p b . Ten p e rce n t of th e in d iv id u a ls ' analyses were above 1000 p p b . A blood PCB value o f 300 ppb ro u g h ly corresponds to a 100 ppm level in fa tty tissu e o f th e same in d iv id u a l, o r a body co n te n t o f about 1.5 gm (1 6 ). By com parison, mean serum PCB backgro u n d levels fo r va rio u s qroups of in d u s tria lly unexposed persons in the U .S. ranqe from 2-24 ppb (26 p .269). In capacitor plants the most fre q u e n t PCB-related health effect ob served was tra n s ie n t skin rashes a ffe c tin g a small percentage o f exposed employees. For example, analysis o f GE medical records o f the F t. Edward and Hudson Falls, N .Y . plants fo r the 1960-1975 period showed a cumula tiv e total o f 49 co n ta ct and a lle rg ic d e rm a titis cases a ttrib u te d to PCB's among an exposed employee g roup to ta llin g about 1300 in d iv id u a ls (5 ). T his condition responded to simple topical treatm ent and employee reassign ment to o th e r w o rk areas. The medical records o f th is w o rk e r population have shown no obvious incidence of systemic disease a ttrib u ta b le to PCB's. A dditional studies (described below) are continuing. O bservations o f high PCB blood leve ls, some dermal co n ditio n s and isolated cases o f chloracne have been reported in the in d u s tria l hygiene lite ra tu re of Japan, Finland, Australia and Italy (2 ,3 ,4 ,6 ,7 ,8 ). The re ported biochemical examinations (2 ,3 ,4 ,6 ,7 ) ide n tifie d scattered ind ividu a l abnorm alities in serum enzymes; however, on a group basis th e various liv e r fu n c tio n tests were considered normal. The Italian chloracne cases of re f. 7 were observed in men who had w orked w here th e level o f A ro c lo r 1254 was measured a t 5200-6800 pg/m 3 (10-14 times th e U .S . T L V ) . Ref. 4 states th a t th e Finnish capacitor w orkers are in good health and th a t, in sp ite o f a p pro xim ate ly 50 times la rg e r PCB co n centration in th e ir blood compared w ith a control gro up , the researchers were unable to detect any biological e ffe c t caused b y PCB in them. In a 1977 U .S . s tu d y 32 capacitor w o rke rs w ere examined in a p ro gram sponsored by the South Carolina State Department of Health and Environmental C ontrol (D HEC ). Newspaper reports (January 1978) quote D r. D .H . Robinson o f th e DHEC as saying th a t th e s tu d y "c le a rly shows th a t at present th e re is no evidence o f physical harm re s u ltin g from w ork ing w ith P C B 's." D r. Ira Rosenblum o f A lbany Medical College, who d ire c te d the s tu d y , is also quoted as s ta tin g , " I t is e xce ed in gly d iffic u lt *The geometric mean of n numbers equals the nth root of their product. For a log normally distributed population the geometric mean equals the median. -14 736785 9eo^oNao Section IV Health Effects of PCB j and PCDF Mixtures i to establish a cause-effect relationship between exposure to PCB's in the workers* environm ent and any sign or symptom o f acute disease o f occupa tional o rig in ( 9 ) . 11 A stu d y of occupationally exposed Bloomington, Ind. capacitor w o rk ers and o ther residents, reported in 1978, did not note liv e r in ju ry , b u t fo u n d th a t levels of GGTP liv e r enzyme and plasma trig ly c e rid e s were p o s itiv e ly c o rre la te d w ith those o f serum PCB's (1 0 ). No co rrela tio ns were observed between serum PCB levels and fiv e o th e r liv e r fu n c tio n in d ica to r s . A le tte r to the s tu d y p a rtic ip a n ts from th e U .S . C enter fo r Disease C ontrol noted th a t human cancer ris k would remain unknown u n til the extensive m o rta lity study (reported below, re f. 15) then being conducted b y NIOSH had been completed. , j i j , A b ro ad e r clinical s tu d y o f 224 Bloom ington, In d . capacitor w orke rs was la te r conducted b y NIOSH. The in v e s tig a to rs re p o rte d in a p re lim in a ry d r a ft (1981) th a t the p la n t employees' serum L-PCB levels* were 8 to 50 tim es, and th e ir serum H-PCB levels* 2 to 4 tim es, the community backgro u n d level (1 7 ). A parallel s tu d y was also conducted of 92 em ployees in two e le c tric u tilitie s , 39 o f whom were a ctive in the m aintenance, re p air and overhaul of transform ers (18). A d ra ft re p o rt covering both studies (63) stated th a t no clinical abnorm alities d ire c tly a ttrib u ta b le to PCB exposure were observed on physical exam ination. Serum SGOT, GGTP, trig ly c e rid e s and HDL-cholesterol were w ith in normal ranges. The fir s t three of these parameters were correlated p o sitive ly, and the last, n e g a tiv e ly , w ith serum PCB levels. One re p o rt at variance w ith th is pattern of clinical studies describes a re c e n tly p u blished s tu d y of 80 Italian capacitor w o rke rs who were c h ro n ic a lly exposed to French and Italian PCB's co n ta in in g 42% ch lo rin e . PCB concentrations in a ir were reported from 48-275 pg/m 3 , and skin absorp tio n was noted. Fifteen o f th e 80 e xh ib ite d skin abnorm alities, in clu d in g 4 diagnosed as chloracne. Sixteen o th e r w o rke rs were judged to show more o r less pronounced hepatic involvem ent, as deduced from symptoms, c lin i cal examination o f the liv e r, and serum enzymes (1 9 ,2 0 ). In 1976 D r. Irv in g S e lik o ff o f M t. Sinai School o f Medicine began a s tu d y o f th e health status o f capacitor w orke rs in th e GE pla n ts at Hudson F a iis /F t. E dw ard, N .Y . T hree hundred tw e n ty -s ix v o lu n te e rs , some o f whom had a long h is to ry o f occupational exposure to PCB's, were given extensive medical examinations. In one paper th e investigators reported average PCB blood levels o f 124 ppb (lo w e r homologs) plus 48 ppb (h ig h e r homologs) and noted a correlation between ind ividu a l values and the e sti mated job exposure. A number o f dermatological fin d in g s were re p o rte d , some o f w hich showed an association w ith blood PCB levels o f the h ig h e r 'L-PCB (lower homologs) and H-PCB (higher homologs) are defined as species having respectively shorter and longer gas chromatographic reten tion times than p,p' -DDE. - 15- 736786 GENP 002037 Section IV Health Effects of PCB and PCDF Mixtures homologs. The a u th o rs noted a p a u city of o th e r abnormal fin d in g s on physical exam ination, in clu d in g a v e ry low prevalence o f abnormal liv e r fin d in g s (1 3 ). In a n o th e r 1979 paper the M t. Sinai g ro u p re p orted th a t 14% o f the w o rke rs examined had abnormal v ita l ( lu n g ) c a p a c ity , compared w ith 5.6% cited fo r M o rris ' non-sm oking normal population (14, 62). We believe the significance o f th is observation is u n ce rta in . Medical s u rv e illa n c e b y General E lectric of a g ro u p o f 174 h e avily e x posed capacitor w orkers has consisted of m ultiple examinations over th e last fo u r ye a rs. The GE se rvice o f th is g roup averages o ve r 15 years, and ranges from 1 to 35 y e a rs . A bout 20% of th is s tu d y population is o verw eight, shows elevated serum trig ly c e rid e s and p e rio d ic, mild eleva tions o f fa stin g blood s u g a r. However, the medical exam inations have not revealed serious health problem s related to PCB e x p o su re . The pulm onary fu n ctio n tests of the non-sm okers in th is heavily exposed population were in the normal range. As p re v io u s ly n o te d , the serum PCB levels in th is g ro u p are high (1979 a rith m e tic mean o f 500 ppb w ith 10% of the in d iv id u a l analyses above 1000 p p b ) and p e rs is te n t. The o n ly clinical param eter th u s fa r found to be s ta tis tic a lly c o rre la te d w ith the serum PCB level is th a t o f serum t r ig ly cerides. The in te rp re ta tio n o f th is correlation is confounded by the fa c t th a t PCB's d is trib u te eq ua lly among all lip id pools in th e body, in clu ding those in th e blood; and hence fo r any given PCB bo dy b urden th e serum PCB level m ust v a ry d ir e c tly as the level o f serum lip id s . A rough c o rre la tio n w hich is em erging from th is s tu d y o f GE capacitor w orkers is th a t people who are exposed to airborne PCB's fo r long periods may show an increase o f about 0.5 ppb in th e ir blood fo r each 1 pg/m 3 present. Thus long-term environmental exposure to a ir containing 2 pg/m3 PCB m ight be expected to add about 1 ppb to an average person's 2-24 ppb PCB backgro u n d le v e l, a small amount compared w ith th e normal background, and in s ig n ific a n t compared to levels reported in heavily e x posed capacitor w orkers (30-3000 ppb re f. 17). 5. NIOSH M o rta lity S tu d y . T h ree p re lim in a ry re p o rts have sug gested a possible epidem iological association between PCB exposure and human cancer (3 3 ,5 5 ,5 6 ). A ll o f these have been regarded as inconclusive because th e y involved small groups o f people, few deaths, uncertain levels o f exposure to PCB's and to o th e r chemicals, s h o rt latency in te rv a ls , and lack o f consistency in cancer site . The International Agency fo r Research on C ancer evaluated th e evidence available th ro u g h 1979 fo r PCB's causing cancer in humans as "in a d e q u a te ", meaning " in s u ffic ie n t to allow any conclusion regarding ca rcin o g e nicity fo r humans" (3 0 ). The FDA's assess ment in 1979, based on re vie w o f both animal te sts and th e human re p o rts , was th a t the question o f ca rcin o g e nicity of PCB's was unresolved, though a m atter w o rth y o f fu r th e r in q u iry (5 7 ). S h o rtly th e re a fte r, more d e fin i tiv e evidence became available from a lon g -te rm NIOSH s tu d y o f tw o PCBexposed capacitor w orker populations. - 16- 736787 i I GENP 0u2038 Section IV Health Effects of PCB and PCDF Mixtures A re p o rt o f th is NIOSH m o rta lity s tu d y (1 5 ), b y fa r the most com p re he n sive ever conducted co ncerning human PCB e xp osu re , provides th e best c u rre n t data on m o rta lity experience. T his re tro sp ective cohort, sta n d a rd ize d m o rta lity s tu d y includes 2567 PCB-exposed h o u rly capacitor w o rk e rs in two p la n ts , one of w hich was th e GE Hudson F a lls /F t. Edward, N .Y . com plex. The c o h o rt was defined as all w orke rs who accumulated a t least th re e months employment in areas of th e p la n t where th e re was p o te n tial fo r exposure to PCB's. Exposure in one p la n t began as e a rly as 1938, in the o th e r b y 1946. A to ta l o f 39,018 p e rso n -ye a rs had been accu mulated by the January 1, 1976 s tu d y c u to ff. Personal a ir samples in th e pla n ts in A p r il, 1977 ranged from 24 to 1260 pg/m 3 and area a ir samples from 3 to 810 pg/m 3 PCB's. T h e . NIOSH s tu d y re p orted th a t th e incidence o f all cancer m o rta lity fo r these p la n t populations was s lig h tly lower than th a t o f the general U .S . p o p u la tio n , o r 39 deaths due to m alignant neoplasms v s . 43.79 e x pected based on national norms adjusted fo r age and sex. For o th e r causes o f death th e fin d in g s were as fo llo w s: from ca rd io va scu la r disease, 60 v s . 62.93 expected; from ne rvou s system disease, 11 v s . 12.55 expected; from accid e n ts, 13 v s . 18.29 e xp ected; and from all o th e r causes, 40 v s . 44.79 expected. Deaths from ail causes were 163 v s . 182.35 expected. No s ta tis tic a lly s ig n ific a n t excesses of sp e cific cancer typ e s were observed, though the authors called attention to fo u r rectal and three liv e r cancer cases (5 o f 7 in one p la n t) . We believe th is observation should be followed up by extension of the study time span, because these reported rectal and liv e r cancer cases are too few to be s ta tis tic a lly mean in g fu l. L iv e r cirrh o sis deaths were h ig h e r than normal in one plant (w ith th e p o s s ib ility of some alcohol association noted) and low er in th e o th e r, w ith th e total co h o rt experience about equal to national norms. None o f the causes of death analyzed demonstrated a clear association w ith latency. There was no clear relationship between increasing lengths o f employment in PCB-exposed jobs and the ris k o f m o rta lity due to cancer o r cirrho sis of the liv e r. While the m o rta lity experience reported in th is paper is re a ssurin g, it should be recognized th a t even th is large stu d y does not y e t encompass enough person-years of experience to exclude the p o ssib ility th a t th e re m ig h t have been increased ris k o f some uncommon ty p e o f disease. F u r th e r, the p la n t populations described were not segregated between those in lig h tly v s . those in more heavily exposed jobs, which m ight have provided more data concerning dose-related differences. 736788 - 17- GENP 002039 Section IV Health Effects of PCB and PCDF Mixtures c. H ealth E ffects S u m m a ry To summarize, there is now available a s c ie n tific lite ra tu re o f several hundred papers de scrib ing many facets of th e biological behavior o f PCB's in animals: routes and rates of uptake and elim ination; bioaccumulation and persistence; enzyme induction; other pharmacological effects; and the effects o f molecular s tru c tu re s o f in d ivid u a l PCB molecules o r im purites on biological a c tiv ity . This lite ra tu re includes e a rly toxicological studies th a t led to recommendations to lim it continuous occupational PCB exposure to 500 o r lOOOpg/m3 (depending on th e degree o f c h lo rin a tio n ). N e a rly 50 years of experience has shown th a t e le c tric a l-g ra d e PC B's, at in d u s tria l occupational exposure levels, are not acutely to xic to humans. A continuing concern about these materials has been potential chronic e ffe cts, since exposure to PCB's leads to accumulation in the body and re te n tio n fo r long time periods. The la rg e s t available source o f data on such effects is presented by capacitor w orker populations. Thousands of such individuals received lig h t to heavy exposures to PCB's o f A ro c lo r types 1254, 1242, and 1016 o v e r many ye a rs , and elevated levels o f PCB's in th e ir blood and fa tty tissues continue to be observed. A number of clinical studies o f such exposed w orke r groups have now been completed (2 ,3 ,4 ,5 ,6 ,7 ,8 ,9 ,1 0 ,1 3 ,1 4 ,1 6 ,1 7 ,1 9 ,2 0 ,6 3 ). Dermal reactions were noted in some cases. These included some ra re observations o f chloracne, especially in pla n ts outside th e U .S . Some studies re p o rt co rrela tio n o f serum enzymes and trig ly c e rid e s w ith serum PCB levels. In sum, the preponderance of these studies n e ithe r id e n tify sig n ifica n t clinical disease associated with e le ctrica l-gra d e PCB e xp osu re , n o r p ro vid e persua sive evidence o f health im pairm ent. In a d d itio n , th e NIOSH s tu d y o f th e long-term m ortality experience of a large group of h o u rly capacitor w orkers at two p lants showed no excess in total m o rta lity , n o r in m o rta lity due to cancer, to cardiovascular disease o r to nervous system disease. A human hazard th a t was not recognized e a rly was th e p o s s ib ility th a t PCB's used in high tem perature en viro n m en ts, such as heat exchangers o r baking operations at 270C and h ig h e r, could be p a r tia lly oxid ize d to PCDF's w ith a consequent increase in to x ic ity . T h is fa c to r makes th e YUSHO episode re t d ire ctly relevant to the usual U .S . occupational o r environm ental exposure. Even in such special cases th e health ris k ap pears to be fin ite . The Japanese and Taiwanese Yusho investigations both p ro vid e evidence that the PCDF th re s h o ld dose fo r in d u c in g Yusho illness s 0 .6 -1 .5 mg. "h is may p ro vid e a benchm ark fo r e va lu a tin g PCDF r is k and fo r considering whether p rotective measures are needed when a PCDF level is id e n tifie c *n an environm ent (a s , f o r exam ple, in a ir w ith PCB's which have been overheated, o r as tra ce q u a n titie s in th e edible p o rtio n o f fis h ) . The avai.sh.e analyses indicate th a t U .S . e le c tric a l-g ra d e PCB's contained 0-2 ppns -CDF's as m anufactured. Such levels may be c o n s id e r- y i - 18- 736789 jENP 002040 Section IV Health Effects of PCB and PCDF Mixtures ed to x ic o lo g ic a lly in s ig n ific a n t since in ta ke o f about a kilogram of such PCB would be needed to acquire a th re s h o ld dose o f PCDF. However, additional measurements are needed to check th e PCDF levels in used PCB's. In view o f the lack of evidence fo r health damage in people w ith heavy PCB exposure in th e past (d a ily skin co ntact and inhalation of a ir con ta in in g 100-1000 pg/m 3 ) , th e re does not p re s e n tly seem to be a su b stantial basis fo r concern about th e effects of exposure to environm ents containing e le ctrica l-gra d e PCB's a t the g re a tly reduced levels ty p ic a lly encountered today. A cco rd in g ly, while a confirmed blood or fa t tissue PCB analysis* s ig n ific a n tly h ig h e r than the local average may indicate exposure, there is little reason to believe th a t s ig n ific a n t adverse health effects w ill o ccur. In the lig h t o f o u r present knowledge th e re is no f u r th e r examination procedure o r th e ra p y which is lik e ly to be m eaningful. While the lack o f evidence fo r serious e ffe cts o f e le c tric a l-g ra d e PCB exposure on capacitor w orkers is encouraging, the studies available today do not completely rule out the p o ssib ility o f subtle o r in fre q u e n t effects in some in d iv id u a ls who were h e a vily exposed in th e p a st, and more o b se r vation time is needed to reduce u n c e rta in ty about the v e ry long-term ex perience o f these people. Concerns about the repro d u ctive experience of h e avily exposed in d ivid u a ls also need to be addressed. The concluding section o f th is paper describes some on -go in g research program s th a t may resolve some o f these u n c e rta in tie s . 'Any unconfirmed single PCB analysis should be regarded cautiously: a recent round-robin study by the N. Y. State Department of Health showed at least one case where 2 out of 10 commercial analyses of the same sample reported PCB values that were 20-fold different from the median. 736790 - 19- GENP 002041 Section V U.S. PCB Regulations The concern about environm ental accumulation of PCB's and about possible human health e ffects Jed in 1976 to th e enactment o f Section 6 (e) o f T S C A . Section 6 (e ) d ire c ts EPA to p re s c rib e PCB m arking and disposal re q u ire m e n ts ; g e nerally bans co ntinued PCB use except in a " to ta lly en closed m a n n e r;" and g e n e ra lly bans PCB m anufacture, processing and d is tr ib u tio n . The PCB Disposal and M arking Rule and the PCB Ban Rule prom ulgated b y EPA to implement Section 6 (e ) contain the fo llo w ing major features (58): Most items th a t contain 50 ppm (0.005%) o r g re a te r PCB must be labeled. A ll liq u ids th a t contain 500 ppm (0.05%) o r g re a te r PCB and PCB-containing capacitors w ith 3 lbs. o r more d ie le ctric flu id must be disposed of in an EPA-approved high te m perature in c in erator. A ll liq u id s th a t contain between 50 ppm and 500 ppm PCB must be disposed o f in an EPA-approved high tem perature in c in e ra to r, in a high e ffic ie n c y b o ile r o r in an EPA-approved chemical waste J a n d fill. P C B -containing capacitors w ith less than 3 lb s . of d ie le c tric flu id may be disposed o f as m unicipal solid waste unless owned b y a capacitor m anufacturer o r m anufacturer o f items th a t contain such capacitors ( e .g ., microwave ovens, electronic equipment and fluorescent lig h t ballasts and fix tu re s ). These manufac tu re rs must dispose o f th e ir P C B -containing capacitors in an EPA-approved high-tem perature incinerator. Waste oil th a t contains any detectable concentration o f PCB's cannot be used as a sealant, coating o r d u s t control agent. Most items and liq u id s th a t contain 50 ppm o r g re a te r PCB and th a t have been designated fo r disposal must be stored in com pliance with specific requirem ents. PCB's contained in intact,- non-leaking capacitors, transform ers and electromagnets are being used in a "to ta lly enclosed man n e r ;" * th e re fo re , such capacitors, transform ers and electromag nets may remain in se rvice. The m anufacture, processing, d is trib u tio n and use o f PCB's in concentrations below 50 ppm may co n tinu e w ith o u t re s tric tio n * . `A recent court decision requires EPA to re-examine this determination. -20- 736791 GENP 002043 ! Section V U.S. PCB Regulations Eleven uses o f PCB's in o th e r than a "to ta lly enclosed m anner" (in c lu d in g se rvicin g tra n s fo rm e rs and electrom agnets and PCB use in existing stocks of carbonless copy paper, in pigments and in heat tra n s fe r and h y d ra u lic system s) may continue su b je ct to certain conditions and time lim its. The FDA has established tolerances fo r unavoidable residues o f PCB's in several classes o f food. Present tolerances are given below (5 7 ): M ilk and d a iry products P oultry Eggs Fish and shellfish (edible p o rtio n ) 1.5 ppm (fa t basis) 3 ppm 0.3 ppm 5 ppm * 'In 1979 the FDA reduced the tolerance for fish and shellfish to 2 ppm, but stayed the effective date of the 2 ppm tolerance pending resolution of objections. GENP Ov/2044 736792 -21- Section VI On-Going Research Programs N o tw ith sta n d in g th e experience o f 50 years usage and the exte n sive research w hich has been com pleted, some questions and u n c e rta in tie s re main. General E le c tric and oth e rs are c o n tin u in g research on some o f these issues. The actual PCDF content o f PCB's in e x istin g capacitors and tra n s form ers as well as in va rious environm ental samples needs to be d e te r mined. Based on the re p orted PCDF content o f A ro c lo rs (0 -2 pp m ), one may postulate th a t PCDF's w iil be detected in such m inute q u a n titie s th a t th e y should not be o f concern. T his postulate needs to be validated by analysis and e va lu a tio n , and GE is conducting an a n alytica l research p ro gram to make such data available. A number o f medical research programs th a t w ill fu r th e r c la rify the possible PCB health e ffe cts are c o n tin u in g . With the cooperation o f Gen eral E le c tric , New Y o rk State's D epartm ent o f Health ( D r . P hilip R. T a y lo r) is analyzing fu r th e r th e epidem iology of the GE ca p acito r w o rk e r popula tio n , and is extending the research to include re p ro d u ctive experience. General E lectric is co n tinu in g medical research w ith a g ro up o f h e avily exposed ca p acito r w o rk e rs ; and some additional o b serva tio n s may become available from the M t. Sinai School of Medicine's studies of other w orkers at th e same location. The Michigan State D epartm ent o f Health ( D r . H .E .B . Hum phrey) is extending and broadening its stu d y o f in d ivid u a ls who have ingested PCB's b y eating fis h . Another question concerns ind u stria l exposures of transform er w ork e rs. T ra n s fo rm e r pla n ts ty p ic a lly used A ro c lo r 1254 and 1260, u su a lly mixed w ith chlorobenzenes, fo r a portion of th e ir p ro du ctio n , whereas A ro c lo r 1260 was not used in ca p acito rs. Few epidemiological studies o f tra n sfo rm e r w orke rs exposed to PCB's are available. The capacitor w orker experience may be re le v a n t, how ever, as A ro clo rs 1254 and 1260 contain s u b s ta n tia lly o v e rla p p in g though not identical populations o f PCB molecules. In a d d itio n , ca p acito r w o rk e r blood analyses show re te n tio n o f th e mole cules contained in A ro c lo r 1260. L a s tly , some research program s are being d ire c te d a t economically e ffe c tiv e PCB containm ent and d e s tru c tio n processes in o rd e r to respond more e ffe c tiv e ly to Federal and State requirem ents. General E lectric is a ctive in some o f these program s. 736793 -22- GENP 002045 Section VII References Cited 1. J .H . H ighland, et al, "M alignant Neglect", A lfre d A. Knopf, New Y o rk , 1979, C hapter 3. 2. Hasegawa, H ., Sato, M ., and T s u ru ta , H ., PCB C oncentration in th e Blood o f W orkers Handling PCB, Occup. H ealth, 10, 50 (1972). ( In Japanese). 3. Kitam ura, M ., Tsukamoto, T . , Sumino, K ., Hayakawa, K ., S hibata, T . , and H irano, I . , The PCB Levels In the Blood of W orkers Employed in a Condenser F actory, Japan J. Ind. H ealth, 7, 354 (1973). (In Japanese). 4. K arppanen, E. and Kolho, L ., The C oncentration o f PCB in Human Blood and Adipose Tissue in Three D iffe re n t Research G roups, Proceedings of PCB Conference I I , Solna, Sweden, 1972, National Swedish Environm ental P rotection B oard, S to ck holm, 1973, p p . 124-8. 5. General E lectric response to in te rro g a to ry #17, N .Y . State Dept, o f Environmental Conservation Proceeding, File No. 2833, Dec. 1, 1975. 6. O u w , H. K ., Simpson, G .R ., and S iy a li, D .S ., Use and Health Effects o f A ro c lo r 1242, a P olychlorinated B ip h e n y l, in an Elec tric a l In d u s tr y , A rc h . E n viro n . H ealth, 31, 189 (1976). 7. P u ccin e lli, V . , On C hloracne, Med. d . Lavoro, 45, 131 (1954) (In Italian). 8. Hofman, M .F ., and Meneghini, C .L ., Concerning Folliculosis Caused by C hlorosubstituted H ydrocarbons, G. Ita l. Dermatol. S ifilo l, 103, 427 (1962) (In Ita lia n ). 9. South Carolina Dept, of Health and Environmental C on trol, S tudy o f Sangamo C apacitor Division W orkers, (Press R e p o rt). Jan. 1978. 10. P olychlorinated B iphenyl Exposure - Indiana, C enter fo r Disease C o n tro l, M o rb id ity and M o rta lity Weekly R ep o rt, M ar. 24, 1978. 11. Michigan D ept, o f Public Health, Final R eport on FDA C ontract 223-73-2209, Evaluation of Changes in the Level of P olychlorin ated B ip h e n y ls (P C B 's ) in Human T issu e , 1975. 12. Hum phrey, H .E .B ., Evaluation o f Humans Exposed to Halogenated B ip h e n yls, Am. Chem. Soc. D iv. E nviron. Chem. P re p rin ts, 20 No. 2, 272 (1980). 736794 - 23- GENP 002046 13. Fischbein, A ., W olff; M .S ., L ilis , R ., T h o rn to n , J ., and Selik o ff, I . J . , C linical Findings among PCB-Exposed C apacitor Manu fa c tu rin g W orkers, A n n ., N .Y . Acad. S c i., 320, 703 (1979). 14. Warshaw, R. Fischbein, A ., T h o rn to n , J ., M ille r, A ., and Selik o ff, I . J . , Decrease in V ital Capacity in PCB-Exposed Workers in a Capacitor M anufacturing F a cility, A nn. N .Y . Acad. S c i., 320, 277 (1979). 15. Brown, D .P ., and Jones, M ., M ortality and In d u stria l Hygiene Study of Workers Exposed to Polychlorinated B iphenyls, A rch. Env. H ealth, 36, 120 (1981). 16. Lawton, R .W ., Ross, M. R ., and Feingold, J . , GE D ra ft R eport (1981). 17. Sm ith, A .B . , Schloemer, J.., Low ry, L .K ., Smallwood, A .W ., Ligo, R .N ., Tanaka, S ., S trin g e r, W ., Jones, M ., and Glueck, C .J ., D ra ft re p o rt: C ross-Sectional Medical S u rve y o f a Group of Workers Occupationally Exposed to Polychlorinated Biphenyls (P C B 's ) at an E lectrical Equipment M a n ufactu rin g P lant, National In s titu te fo r Occupational Safety and Health, Division o f S u r ve illa n ce , Hazard Evaluations and Field S tu d ie s, C in c in n a ti, OH 45226, and Lipid Research C enter, U n iv e rs ity o f C incinnati Medical C e n te r. C in c in n a ti, OH 45267, 1981. 18. Sm ith, A .B . , Schloemer, J ., Low ry, L .K ., Smallwood, A .W ., Ligo, R .N ., Tanaka, S ., S trin g e r, W., Jones, M ., H ervin, R ., and G lueck, C .J ., D ra ft re p o rt: C ross-Sectional Medical S urvey of Two Groups of Workers Occupationally Exposed to P olychlorin ated B iphenyls (P C B 's) in the Maintenance, Repair, and O ver haul of E lectrical T ra n s fo rm e rs , ib id . , 1981. 19. M aroni, M ., Colombi, A ., C antoni, S ., Ferioli, E ., and Foa, V ., Occupational Exposure to Polychlorinated Biphenyls in Electrical W orkers. I Environmental and Blood Polychlorinated Biphenyls C on ce n tra tio ns, B r it. J. In d . M ed., 38, 49 (1981). 20. M aroni, M ., Colombi, A ., C antoni, S ., F e rioli, E ., and Foa, V ., Occupational Exposure to Polychlorinated B iphenyls in Electrical W orkers. II Health E ffe cts, ib id . , 38, 55 (1981). 21. NIEHS Conference on Polychlorinated B iphenyls , E n viro n . Health Perspec., 1, (1972). 22. NIEHS C onference on C hlo rin a te d D ibenzodioxins and D ibenzofu ra n s, E nviron. Health Perspec., 5, (1973). 23. Proceedings o f the National C onference on P o lychlo rin a te d B ip h e n yls, November 19-21, 1975, Chicago, I I I . , EPA - 560/6-75-004, M arch, 1976. GENP ^ 2 0 4 7 - 24- 736795 24. Health Effects of Halogenated Arom atic H ydrocarbons, A nn. N .Y . Acad, of S ci., 320, (1979). 25. Proceedings o f the C onference "PCB's Impacts on H e a lth ,11 Sep tem ber 12, 1979, H a rtfo rd , Conn. T ra n s c rip t by Conn. Dept, of Environm ental P rotection, O ct. 1, 1979. 26. "Halogenated Biphenyls, T e rp h e n yls, Naphthalenes, Dibenzodioxins and Related P ro d ucts", Kim brough, R .D ., E d., E lse vie r/ N orth Holland Biomedical P ress, Am sterdam , 1980. 27. Fishb'ein, L ., T o x ic ity of C hlorinated B iphenyls, A nn. Rev. P h a rm aco l., 139 (1974). 28. C rite ria fo r a Recommended S ta n d a rd : Occupational E xposure to P olychlorinated B iphenyls (P C B 's ), DHEW (N IO S H ) P ubl. 77-225, S e p t., 1977. 29. Polychlorinated Biphenyls and Polybrominated B iphenyls, In te r national Agency fo r Research on Cancer M onographs, 1_8, (1978). 30. In te rn a tio n a l Agency fo r Research on Cancer M onographs, S up plement 1 to Vols. 1-20, (1979). 31. Buser, H .R ., Bosshardt, H .P ., and Rappe, C ., Formation of 'Polychlorinated D ibenzofurans (PC D F's) from the P yrolysis of PC B's, Chemosphere, J_, 109 (1978). 32. G oldstein, J .A ., The S tru c tu re -A c tiv ity Relationships of Halo genated B iphenyls as Enzyme In d u c e rs , A n n . N .Y . A cad. S c i., 320, 164 (1979). 33. Monsanto C o., Submission to the Subcommittee on O ve rsig h t and In v e stig a tio n s of the Committee on In te rs ta te and Foreign Com merce, U .S . House o f R epresentatives, Nov. 16, 1979. 34. "P C B 's in the United S tates; In d u s tria l Use and Environm ental D is trib u tio n " , V e rs a r, In c . EPA C o n tra ct No. 68013259. U .S . D ept, o f Commerce, NT1S PB 252012, Feb. 25, 1976. 35. Vos. J .G ., Koeman, J .H ., van der Maas, H .L ., ten Noeverde de B rauw , M .C . and de Vos, R .H ., Id e n tifica tion and Toxicological Evaluation of Chlorinated Dibenzofuran and Chlorinated Napthalene in Two Commercial P olychlorinated B ip h e n yls, Fd. Cosmet. T o x ic o l., 8, 625 (1970). 36. Vos, J .G ., and Beems, R .B ., Dermal T o x ic ity Studies o f T e ch nical Polychlorinated Biphenyls and Fraction Thereof in R abbits. T o xico . A p p l. Pharm acol., 19 617 (1971). GENP 002048 - 25- 736796 37. Bowes, G .W ., M u lvih ill, M .J ., Simoneit, B .R .T ., Burlingam e, A .L ., and Risebrough, R .W ., Identification of C hlorinated Dibenzofurans in American Polychlorinated B ip he n yls, N ature, 256, 305 (1 9 75 .) 38. D rin k e r, C .K ., W arren, M .F ., B ennett, G .A ., The Problem of Possible Systemic Effects from Certain C hlorinated H ydrocarbons, J. In d . H yg. T o x ic o l. 19, 283 (1937). 39. T reon, J .F ., Cleveland, F .P ., Cappel, J.W. and A tch le y, R .W ., The T o x ic ity o f the Vapors o f A ro c lo r 1242 and A ro c lo r 1254, Am. In d . H yg. Assoc. Q u a rt, 17, 204 (1956). 40. Burse, V .W ., Kimbrough, R .D ., Villanueva, E :C ., Jennings, R .W ., L in d e r, R .E ., and Sorocool, G ., Polychlorinated Biphen yls, Storage, D istribution, Excretion, and Recovery: Liver M orphology A fte r Prolonged D ietary Ingestion, A rc h . E nviron. H ealth, 29, 301 (1974). 41. Kim brough, R .D ., Linder, R .E. and Gaines, T . B . , Morphological Changes in L ive rs o f Rats Fed P o lychlorinated B ip h e n y ls , L ig h t M icroscopy and U ltra s tru c tu re , A rc h . In d . H ealth, 25 354 (1972). 42. Kim brough, R .D . and Linder, R .E ., Induction of Adenofibrosis and Hepatomas o f th e L ive r in BA LB /C J Mice b y P olychlorinated B ip h e n y ls (A ro c lo r 1254), J. N atl. Cancer I n s t. , 53, 547 (1974). 43. Kim brough, R .D ., Squire, R .A ., Linder, R .E ., S trandberg, J .D ., M ontali, R .J. and Burse, V .W ., Induction o f L ive r Tumors in Sherman S tra in Female Rats b y P o lychlo rin a te d B iphenyl A ro c lo r 1260, J . N atl. Cancer In s t. , 55, 1453 (1975). 44. "B ioassay o f A ro c lo r 1254 fo r Possible C a rc in o g e n ic ity .11 C a rcin ogenesis Program, D iv. of Cancer Cause and P revention, N at'l. Cancer In s t., R eport No. (N IH ) 78-838, (1978). 45. Testim ony o f th e General E le c tric Company, OSH A Carcinogen Policy H earing, Wash., D .C ., D r. T .R . Casey, V ice-P resident. C ancer Policy OSH A Docket H-090, Ex. 152. J u ly 20, 1978. 46. General E lectric Co. comments re R egulatory Council statem ent on R egulation o f Carcinogens (44 FR 60038), N ov. 13, 1979, J .F . Young, V ice-P resident; and sim ilar comment addressed to the Interagency Research Liaison G roup, Nov. 28, 1979, and to the EPA, Feb. 21, 1980. 47. Jones, J.W ., and Alden, H .S ., An Acneform Dermatergosis, A rc h . Derm at. S y p h ilo l, 33, 1022 (1936). 48. Zack, J .A . and Suskind, R .R ., The M o rta lity Experience of Workers Exposed to Tetrachlorodibenzodioxin in a Trichlorophenol Process A c c id e n t, J. O ccupat. M e d ., 22, 11 (1980). GENP 002049 - 26- 736797 m . 49. Meigs, J .W ., Albom , J . J . , and K a rtin , B . L . , Chloracne from an Unusual Exposure to A ro c lo r, J. Am. Med. A s s o c ., 154: 1417 (1954). 50. Birmingham, D .J ., Occupational Dermatology: C u rre n t Problems, S k in , 38 (Feb. 1964). 51. Kuratsune, M ., Yoshimura, T . , Matsuzaka, J ., and Yamaguchi, A ., Epidemiologic S tudy on Yusho, A Poisoning Caused by Ingestion o f Rice Oil Contaminated w ith a Commercial B rand o f P olychlorinated B ip h e n y ls , E n viro n . Health P e rsp ec., ]_f 119 (1972). 52. K u ratsune, M ., Masuda, Y ., and Nagayama, J . , Some of th e Recent Findings C oncerning Yusho, Proceedings o f the National Conference on P olychlorinated B ip h e n y ls , November 19-21, 1975, Chicago, III. EPA-560/675-004, M arch, 1976, p. 14. 53. Food and D rug A d m in is tra tio n , "P o lych lo rin a te d B ip he n yls (P C B 's ); Unavoidable Contam inants in Food and Food Packaging M aterials; Reduction o f Tem porary T o le ra n ce s," Fed. R egister 42, 17488 (1977). 54. Kamps, L .R ., T ro tte r, W .J., Young, S .J ., Carson, L .J ., Roach, J .A .G ., Sphon, J .A ., Tanner, J .T ., and McMahon, B ., Poly chlorinated Q uaterphenyls Id e n tifie d in Rice Oil Associated w ith . Japanese "Y usho" P oisoning, B u ll. E n v iro n . Contam. T o x ic o l., 20 589 (1978). 55. Bahn, A .K ., Rosenwaike, I ., Herrmann, N ., G rover, P ., S te llman, J ., and O 'L e a ry, K ., le tte r, "Melanoma A fte r Exposure to P C B 's", New Eng. J. M e d ., A ug. 19, 1976; Lawrence, C . , Comment, "PCB? and Melanoma"; Bahn, A .K . et a l., re p ly , ib id . , Jan. 13, 1977. 56. Urabe, H ., Koda, H ., and Asahi, M ., Present State of Yusho P atients, N .Y . A cad, of Sei. A n n ., 320, 273 (1979). 57. Food and D rug A d m in is tra tio n , "P o lych lo rin a te d B iphenyls (P C B 's ); Reduction of Tolerances, Fed. R egister, 44, 38330, June 29, 1979. 58. Environmental Protection Agency, "P olychlorinated Biphenyls (P C B 's) M anufacturing, Processing, D is trib u tio n in Commerce, and Use P ro h ib itio n s , Fed. R e g iste r, 44, 31514, May 31, 1979. 59. Lan, C ., Shieh, L ., Chen, P .H ., Chen, Y ., An Epidemiological S tudy on Polychlorinated B iphenyls Poisoning in Taichung Area, C lin . Med. (T a ip e i), 7, 96 (1981). 60. Chen, P .H ., Chang, K .T ., and Lu, Y .D ., T oxic Compounds in th e Cooking Oil w hich Caused PCB Poisoning in Taiw an. I . Levels of Polychlorinated Biphenyls and Polychlorinated D ibenzo fura n s, i b i d . , 7, 71 (1981). - 27- 736798 GENP 002050 61. K reiss, K ., Zack, M .M ., Kimbrough R .D ., Needham, L . L . , Smrek, A . L . and Jones, B . T . , Association of Blood Pressure and P olychlor inated B iphenyl Levels, J . Am. Med. A sso c., 245, 2505 (1981). 62. M orris, J .F ., Kolski, A. and Johnson, L .C ., Spirom etric Standards fo r H ealthy Nonsmoking A d u lts , Am. Rev. R e s p ir t. D i s . , 103, 57 (1971). 63. Sm ith, A . B . , Schloemer, J ., Low ry, L . K . , Smallwood, A .W ., Ligo, R . N . , Tanaka, S ., S trin g e r, W ., Jones, M ., H e rv in , R. and Glueck, C . J . , Metabolic and Health Consequences o f Occupational Exposure to Polychlorinated Biphenyls (PCB's), NIOSH, Div. of S urveillance, Hazard Evaluations and Field S tudies 4676 Columbia P k w y . , C in c in n a ti, OH 45226, and L ip id Research C en ter, U n iv . o f C in c in n a ti Medical C e n te r, C in c in n a ti, OH 45267 (1981). i 736799 GENJ. 002051 GENPC .052 T his paper has been prepared fo r use w ith in the General E lectric Company Corporate Health and Safety Operation GENERAL ELECTRIC 736800