Document XRXogwEGYGRazkQpa1J6qJVrR

subject to ready oxidation in the body. Similar MFO elevations are caused by certain drugs, hydrocar bons, and other substances. H olth Effects Observed Only In Test Animals Several health effects have been observed in test animals, but have not been observed in people, even after many years of occupational exposure. They are: 1. The 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 studies oP occupational Ivexposerl workers thp tect rp^lK were also negative with an exception of a single report of excess skin Tancer in one group ot workers. 1 His report was not confirmed in other studies. It can be concluded that there' are no demonstrated connec tions between PLH exposure and dancer in neonle. even when occupationally exposed. 2. Adverse effects on reproduction Have been observed in experimental animals, generally at very high dosages. They are: ~ a. Effects of PCBs on the develop ing embryo or fetus leading to birth defects (teratological ef fects) have been observed in a limited number of experimental animals. I b. Toxic effects on the developing fetus in test animals can be pro duced by high dosages of PCB. No evidence for such effects in ppnplp has hppn rProrHpd pvap jnr prppnant wnmpn nrrnnatinnaliv- exposed to PCBs. It is concluded that {fie probability of such effects occur ring in people is vp<~y " 3. PCBs are able to produce adverse ef fects on liver tissues in test animols, reversible at low doses and increas ingly irreversible at higher exposure levels. No adverse effects on liver functions have been objmyed \n occupationally pxnospH^Birke^- Ieading to the conclusion that these chemicals do not cause human livqr qisease under these conditions. 4. PCBs exhibit a low to moderate degree of acute toxicity in test animals. However, there is little evidence in people ofany acute tox icity in the course of PCB intakestorage in tissues, metabolism ajr>H excretion. Further, there is no evidence to ind irate fhp PCR;_pjx- duce any adverse effects human immune cygtem nr plnqd supply^ Other Observations and Conclusions Mutagenesis: The possibilities of harmful, heritable changes in genetic fhaterial of cells and tissues unaerlTie action of PCBs have been studied in biological test systems, ex^imental animals, and occupational^Vcposed workers. All test results are negative for such changes. The risk of genetic damage i in people from PCB exposure is negligi ble. This conclusion is consistent with the lack of a demonstrated connection between PCB exposure and cancer. Yusho Disease: Because of the unique ness of the Yusho episodes in terms of the level of contamination of the PCBs, the dosage patterns and the symptoms observed, Yusho cannot be considered a model to reflect the possible effects of PCB exposure in man. It is impossible to stipulate whether any of the health ef fects observed are causally related to PCB exposure. Summary At human exposure levels as high as those previously encountered in occupTtional settings, PCBs can cause chloracne and increases in the levels of one or more liver enzymes. Neither effect represents^ serious or life-threatening health prob lem. From present evidence, no firm associations can be made between PCB exposure and any other human health ef fects, even after long-term occupational exposures. Since the risk to human health from even high level occupational exposures has been shown by the studies available to be low, it may be concluded that much lower human exposures to PCBs i today's workplace and in the natural en vironment do not present signifies human health risks. For the Firm, Seymour L. Friess, Presiden March 9, 1982 % S icn x>> -o `oo CO LQO. Cb(0D. Coba>.L >- T3J .c2oP a> <tcuvj "cao wmi-- co ic/ui aou >>4++--) JCCO iS) TcJ -0P) .2 o <I/U) --O1 <U </T to CL- X +Oj -Xtn C 2_Q2 ab.i tLoj_ tcc1j/u1 Tc(J0 < LU 2 O 4-1 _a> -Qc>aCaO -Uti/*i -CCuD CU CO 5 2101 L Street, N. W. Washington, D. C. 20037 loa/> cu E<0 z >c CaO Eo iinn CbU. TJ TJ u< SL 029498 JDFHL&SJ Highlights of the Potential Health Effects in the Human From Exposure to Polychlorinated Biphenyls (PCBs) and Related Impurities Executed for the National Electrical Manufacturer^^hociation and the Edison Electric Institute by Drill, Friel^^eyes, Loomis and Shaffer; Consultants in Toxicology 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 major types: first, results from large numbers of studies in which laboratory test animals were ex posed to graded dosages of PCBs for variable time periods; second, data on effects detected in occupationally exposed workers as deduced from epide miological and clinical studies. In the major recent studies, which are continu ing, several thousands of occupationallyexposed 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 serious, have been observed in workers occupationally exposed to PCBs and in experimental animals. They are: 1. ... A skin disorder known as chloracne. The intensity of this effect is" related 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 proteins (enzymes) known as mixed function oxidases (MFOs) are produced, chiefly in the liver. This condition, even following extended industrial exposures, is not of <}jgnifiranpg tr> Vmalrh nupr "the |jfpfjm a PrR~ exposed person. At most, elevated MFO levels can cause changes in the required dosages of medicines or other therapeutic agents that are SL 029499