Document ymy2Q6da5aapMGM8eokax9X14

SL 029494 ui'jeii to ic,.dy oxidation in the; body. Similai MFO elevations are Caused Ascertain drugs, hydrocar bons, aiuffltlier substances. observed! Oi'ii- Li Tost ;>.iimcils Several health (effects have been oliseo'ed in test animals, but have not been observed in people, even after mam, yents of occupational exposure. 1 hey arts 1. i lie possibility that exposure to PCBs can lead to cancer has been studied in test animals and in exposed peo ple. The bulk of the studies on animals yielded negative results on cancer in all tissues in all species, with an exception of some unverified results on liver cancer in mice and rats'.'" rif studies oPoccupationahyexposocj workers, `Tf^'.testlresplts ' were also negative with an exception "of a " sThgle^Leport of~~excess skin T:ancertn^oneTTroup of workers. I Ifis report" was not confirmed in other studies. It cah'~fje" concluded that there' are no demonstrated connec11ons_between ~PCB exposure and cancer__m_ pJ'SlilPr even when occupationally exposed. 2. Adverse effects on reproduction Have been observed in experimental animals, generally at very high dosaegs. They are: * a. Effects of PCBs on the develop ing embiyo or fetus leading to birth dei-'cts (leratological efh't ts) have been observed in a limited number of experimental ,, animals I b. ! > is uii Hie developing 1 m Uest animals can be pro duced ^wigh dosages of PCB. _N_o evidence for such effects_Jn *ptyo I > !.eJ iasLhfieajQtt{fitH cvetufy r p re j; n a tyt__wpaieo__ Qccupati analLyexposed trpfCBs. It is concluded that tlie p rob a b i! i ty of such ^effect s or cy rling iri~peopTTy is .yekyJow. 3. PCBs are able to produce adverse ef fects on liver tissues in test animals, reversible at low doses and increas ingly irreversible at higher exposure levels. No adverse effects .anJiver functionsT'Tiave been observed_jn pec u p_a|To n51 lyZHci.Q5d_vy.f?jJi?Ji, leading to the conclusion that these chemicaIsjjopot cause humatTlfver 'disease under these conditions. 4. PCBs exhibit a low to moderate degree of acute toxicity in test animals. However, there is little evidence in people of any acute toxiafv'~j7r~the course ofpTTB intake. Storage in tissues,, m eta bo I ism-and excretion. Further, there is no evidence to indicate..the PCB-S-qcoduce any adverse effects on--the Fiuman__immime system., or blood supplE Other Observations and Conclusions Mutagenesis: The possibilities of harmful heritable changes m^genetic material dfcells and tissues under Hie aclioh'of PCBs have been studied in biological test systems, experimental animals, and occu fiat ion ally-exposed worker;. All test results are negative for such t lunges. The risk of genetic damage H1 people It i i , ble. "I bis rtjnt liisiMN is ,i lack of a demoi^Mied coif,.' tween PCB expos^m and earn, w Vus/io Disease: Because of th ness of the Yus ho episodes in iw level of contamination ot ih. } dosage patterns and flu observed, Yusho cannot be t on model to reflec t the possihl.PCB exposure in man. It is impi stipulate vvbetliei any of tlw I fects observed are c ausally n PCB cxposuie. Summary At human exposure levels as those f?reviqiis!y _ena>uTitere d in tionalsettings, PCBs can cause > aricJ ini creases indie leveisof oiv Iiver enzymes. Neither offert rep. serious or life-threatening hen! leniT From present evidence, associations can Be made Brie "exposure and any other human i Tectsf even after long-term u. <i "exposures." Since the risk (o human h even higli level occupational has been shown by the studies to be low, it may be cone ha much lower human exposuies u today's workplace ami in tin- n, vironment do not present s> human health risks I U!' t i H 1 r H JI !. - 1 ! i1 j! March'- r :: % i <} Highlights of the lial Health Effects i the Human on Exposure to 'iychlorinated -phenyls (PCBs) dated Impurities ' Hi. I If'iiin il M-inuLa* Assoria- i ! { til; [nslrtuin hy Huff. I rifts ^ f Uvyps, f i 'nMill,mK in I o\u nlojjv Introducti n Mixtures of chemicals known as polychlorinated biphenyls (PCBs) were manufactured commercially in the United States until 1977 and they are used throuyhout the world in a variety of applications. Over the years, people have been exposed to these chemicals both in the workplace and in the natural environment. Exposures in the work place were generally far more intensive, especially in terms of inhalation and skin contact, than the typical low-level or occasional exposure in the natural environment. Much information on possible health effects resulting from PCB exposures has accumulated in the scientific literature, starting back in the 1930s. This report reviews this informa tion and uses it as the basis for an objec tive assessment of the potential health effects of PCBs on people. Methodology of the Study Two teams of specialists, representing the disciplines of medicine, toxicology, pharmacology, biochemistry and epide miology, participated in the study. The first team reviewed the PCB health ef fects literature in detail through 1981, and prepared draft reports on the rela tionships between PCB exposure and specific health effects in test animals and in exposed people. The second team of scientists from universities indepen dently reviewed the draft material. Con clusions and opinions in the final report reflect contributions from both teams. The health effects information re viewed was of two major types: first, results from large numbers of studies in which laboratory test animals were ex -V; posed to graded dosages oi i'( P- !>>n variable time periods; second, daCi mi effects detected in occupationally exposed workers as deduced from cpiil- miological and clinical studies. In the major recent studies, which are continu ing, several thousands of occupationalh/ exposed workers are being followed From the entire collection of data on people and test animals, conclusions and opinions as to the possibility of occur rence of specific potential health effects in people from exposures to PCBs have been drawn. The results fall into two categories of effects, as follows: Health Effects Observed in People and Animals Two health effects, neither of them sgQQitf, have been observed" in workers occupationally exposed to PCBs and in experimental animals. They are: 1. ... __skin disorder known as chloracne. The intensity of this effect irTefated to degree of exposure and to PCB chemical structure. Chlor acne diminishes on termination of ex posure, and is_ not a serious he a 11 h problem. 2. ... In the process of metabolizing PCBs, excess amounts of proieins (enzymes) known as mixed function oxidases (MFOs) are prodmrd, chiefly in the liver. This ..condition, even following extended industrial exposures, is noljnf significance la heaTthjoyor,,tHeJif clime, of a P C B exposed person. At most, elevated MFO levels can cause changes in the required dosages of mediem-'s or other therapeutic agents that ue SL 029495 Highlights of the entiai Health Effects in the Human From Exposure to Polychlorinated .Biphenyls (PCBs) i Related Impurities , ; - iU'm,il I Fh frii il M.irmh)i turrrs Assoda- f 1 - it J Fu Jrii l>y Pull, f'riess, Hnyes, 11 11; i c ( t instill il I oxh n|t>j;y Introduction Mixtures of chemicals known as polychlorinated biphenyls (PCBs) were manufactured commercially in the United States until 1977 and they are used throughout the world in a variety of applications. Over the years, people have been exposed to these chemicals both in the workplace and in the natural environment, Exposures in the work place were generally far more intensive, especially in terms of inhalation and skin contact, than the typical low-level or occasional exposure in the natural environment. Much information on possible health effects resulting from PCB exposures has accumulated in the scientific literature, starting back in the 1930s. This report reviews this informa tion and uses it as the basis for an objec tive assessment of the potential health effects of PCBs on people. Methodology of the Study Two teams of specialists, representing the disciplines of medicine, toxicology, pharmacology, biochemistry and epide miology, participated in the study, The first team reviewed the PCB health ef fects literature in detail through 1981, and prepared draft reports on the rela tionships between PCB exposure and specific health effects in test animals and in exposed people. The second team of scientists from universities indepen dently reviewed the draft material. Con clusions and opinions in the final report reflect contributions from both teams. The health effects information re viewed was of two j^jor types: first, results from large nu^Bbrs of studies in which laboratory test animal ere ex posed to graded dosages of i',i Ms'fui variable time periods; second, data on effects detected in occup.it tonally exposed workers as deduced from -pule miologicai and clinical studies. In the major recent studies, which ace ( online ing, several thousands of oorupaiii noily exposed workers arc1 being follov >d. From the entire collection of data on people and test animals, conclusions and opinions as.to.the possibility of occur rence of specific potential health effects in people from exposures to PCBs have been drawn, The results fall into two categories of effects, as follows: ^ <(7> Health Effects Observed o In Peorple and Animals cjn Two health effects, neither of them serjoLi^. have been observed in workers occupationally exposed to PCBs and in experimental animals. They are: 1. . . . j\__skm_disorder known as chloracne. The intensify of lhis. effect iiTreTated to degree of exposure and to PCB chemical structure Chlor acne diminishes on termination of ex posure, and is not_a_ serious health problem. 2. ... In the process of metabolizing PCBs, excess amounts of protcim (enzymes) known as inked function oxidases (MFCs) are produced, chiefly in the liver. This ..condition, even following extended industrial exposures, is not of ..significanoe to heaJjth...pve[,,tFie .lifetime of a PCU- exposed_per.50U, At most, elevated MPO' levels can cau^thange, in tie required dosages o other therapeutic agents that am SL 029497 Ji>; .. I ItJ ti.'iKl) oxidation m lilt* body Similar MFC elevations are caused by certain drugs, hydrocar bons, and other substances. a-udii briefs Gbst&rved ,tly tit Vui:i Animals Several health effects have been served in test animals, but have not en observed in people, even after .my years ol occupational exposure, icy are; I he possibility that exposure to PCBs can lead to cancer has been studied in test animals anti in exposed peo ple. 'The bulk of the studies on animals yielded negative results on cancer in all tissues in all species, with an exception of some unverified results on liver cancer in mice .apd ra fs"`"' nV studies"or1 occupational Iydxjaosed workers, the test, .results were also negative with an exception oPa*"single deport oPexcess skin cancefTifone grpun of workers, 'l iTts report* was not confirmed in other studies. It can be "concluded that there' are no demonstrated conneclions betvveen _ PC B"~~"exposTT~e~"a*nd c a pecr__j n__ peon ip, even when occupationally exposed. Adverse effects on reproduction have been observed in experimental animals, generally at very high dosages. They are: " a 1: fleets of PC Us on the develop ing embryo or fetus leading to hi;(b defects (teratological efl. i is) have been observed in a 'aimed number of experimental b. Io.mi i-. on the deveinping fetus in u-st animals can be pro duced by high dosages of PCB. No -ey.iden<;e ..for. such_effects in * egn I r pregnan t ,,.\yjQ m e u__accupaiio oa Uy- exposed toJ^CBs. It is concluded that 11ie"probabHity of such effects oerpr- ring in peo[)feTs_veiy--lQW. 3. PCBs art.* able to produce adverse ef fects on liver tissues in test animals, reversible at low doses and increas ingly irreversible at higher exposure levels. No_ adverse effects on liver functions "Have been observed in occupatio oil I - leading to the conclusion that these c h e mica I sid;aji QL^iSgJ^niflaliYe r disease under thesgjonditions, 4. PCBs exhibit a low to moderate degree of acute toxicity in test animals. However, there is little evidence in people of any acute fgxiafvjrPthe course of PCB intake. excrelfop! FuTther, there is no evidence to indicate the PCBs-dcqduce any adverse effects nn-J:bp Rum anPmmune system qr h|ftod Other Observations and Conclusions Mutagenesis: The possibilities of harmful, heritable changes in genetic mate rial of"cells and tissues under "die action*" of PCBs have been studied in biological test systems, experimental animals, and occupationally-exposed workers. All tost Jesuits arc* negative for siu h c badges The risk of genetie'ei.linage in people Hum . > i > e .p* ,u. , ., ble. f his conclusion is conSYstenfwii lack of a demolish a ted cornier*ao tween PCB exposure and camm Yusho Disease: Because of the m ness of the Yusho ej)isodes in lei ms < level of contamination of the (VIC dosage patterns and the symp observed, Yusho cannot he con'.id model to reflect the possible ell. PCB exposure in man. It is impnail stipulate whether any of the heali fects observed are causally rehiP PCB exposure. Summary At human ex[)osure levels as lit; those previous I y on Jo ujntpred In cur tional settings, PCtis can cause chloi andjncrocistis m the levels of one ot i liver enzymes. Neither effect rejm-s. serious or life-threatening health i lerrJ From present evidence, no associations can bo made between "exposure and any other human heali Tecfs7"ev(;n"after long-term orcupnit "exposlires. Since the risk to human heahh even high level oc< upational r\ni has been shown by the studies avail to be low, it may be concluded much lower human exposures to PCI today's workplace and in the na!ur vironment do not present Memo human health risks For the I inn. 1 - (l, i. j it-, Marr h n, in,"..'