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PRIVILEDGED AND CONFIDENTIAL DRAFT (2/24/86)* Environmental Protection Agency Docket No. OPTS-83002 COMMENTS ON EPA'S NATIONAL PRIMARY DRINKING WATER REGULATION FOR PCBS Submitted by the Polychlorinated Biphenyls Program Panel of the Chemical Manufacturers Associations Geraldine V. Cox, Ph.D. Vice PresidentTechnical Director Langley Spurlock, Ph.D Manger PCB Program Panel Of Counsel: David F. Zoll Vice President General Counsel Timothy S. Hardy Kirkland & Ellis 655 Fifteenth St., N.W. Suite 1200 Washington, D.C. 20005 March 13, 1986 CHEMICAL MANUFACTURERS ASSOCIATION 2501 M Street, N.W. Washington, D.C. 20037 (202) 887-1100 PCB-ARCH-EXT0371860 COMMENTS OF THE CHEMICAL MANUFACTURERS ASSOCIATION ON EPA'S PROPOSED NATIONAL PRIMARY DRINKING WATER REGULATION FOR PCBS Table of Contents INTRODUCTION...................................................................................................... I. THE ONLY EVIDENCE THAT PCBS ARE CARCINOGENIC IS FROM ANIMAL STUDIES THAT ARE LIMITED AND INCONCLUSIVE............................... A. Epidemiologic Studies of Highly Exposed Worker Populations Have Found No Significant Cancer Increases................................................................................... B. Contrary to EPA's Discussion, PCBs Have All Been Found to Be Non-Mutagenic........................................................................ C. The Inconsistent Eioassay Results Show No More Than Limited, Inconclusive Evidence of AnimalCarcinogenicity......................................... II. UNJUSTIFIED EXPENDITURE OF SOCIETAL RESOURCES WOULD BE MANDATED BY ESTABLISHMENT OF A ZERO RMCL FOR PCBS............................................................................................................... CONCLUSION ......................................................................................................... Page 1 2 2 4 6 9 10 PCB-ARCH-EXT0371861 PRIVILEGED & CONFIDENTIAL DRAFT 2/24/86 COMMENTS OF THE CHEMICAL MANUFACTURERS ASSOCIATION ON EPA'S PROPOSED NATIONAL PRIMARY DRINKING WATER REGULATION FOR PCBS INTRODUCTION The Chemical Manufacturers Association (CMA) PCB Pro gram Panel welcomes this opportunity to comment on EPA's proposed National Primary Drinking Water Regulations. 50 Fed. Reg. 46936 (Nov. 13, 1985). CMA's PCB Panel has been an active participant in numerous EPA rulemakings, par ticularly pursuant to the Toxic Substances Control Act (TSCA), concerning PCBs. Throughout its history, the Panel has worked closely with EPA to assure that any PCB regula tions are both protective of public health and consistent with reasonable assessment of potential risks. As detailed in these comments, we urge that EPA revise its proposal establishing a Recommended Maximum Contaminant Level (RMCL) of zero for PCBs in drinking water. EPA errs in its conclusion that PCBs are a Category I probable human carcinogen. To the contrary, there is only limited, incon clusive evidence of animal carcinogenicity. Accordingly, an RMCL of zero is unjustified. We propose that the Agency instead, rely on significant work of the Food and Drug Ad ministration (FDA) to assess potential risks of PCB in the diet and, following its lead, adopt an RMCL of at least 6.5 micrograms (ym) per liter. PCB-ARCH-EXT0371862 -2- I. THE ONLY EVIDENCE THAT PCBS ARE CARCIN03ENIC IS FROM ANIMAL STUDIES THAT ARE LIMITED AND INCONCLUSIVE. Extensive data exi on PCBs. Highly exposed worker populations have been studied, and the compound has been administered in a wide variety of toxicology studies. Based upon this extensive data base, it is possible to reach rea sonable conclusions about any potential risk that might be posed from the presence of PCBs in drinking water. Although it is not possible to conclude that absolutely no adverse health effects would be expected, more than enough data ex- is to indicate that EPA would err by concluding that it should establish a PCB RMCL of zero. A. Epidemiologic Studies of Highly Exposed Worker Populations Have Found No Significant Cancer Increases. __________________ Several epidemiology studies of highly exposed worker populations have found no significant cancer increases. 1/ Studies by Brown and Jones and by Bertazzi, jet al., of 2,567 1/ Earlier reliance on studies in Yusho is no longer considered appropriate. Yusho Oil is not representative of PCB heat transfer fluids, as it contained, in addition to PCBs, high levels of polychlorinated dibenzofurans and polychlorinated guarterphenyls. In consideration of these facts, several scientists have concluded that PCBs were not the cause of poisoning in Japan or Taiwan. See Kuratsune, "Yusho," in Ealogenated Biphenyls, Triphenyls, Napthalenes, Dibenzodioxins and Related Products (1980); Chen, et al., (Footnote Continued) PCB-ARCH-EXT0371863 -3- and 1,310 workers, respectively, exposed for up to more than 20 years, have not demonstrated any consistent relationship between exposure to PCBs and the development of any particu lar cancer. 2/ In addition, the more recent epidemiological review by Lawton, et al., 3/ of medical records of General Electric workers with PCB exposure in electrical capacitor manufacture found only minor dermatological effects, unre markable physical examinations, and no signs of chloracne past or present. The study demonstrates that extensive ex posure to PCBs in the occupational setting, sufficient to have established blood levels in excess of 200 ppb, has not led to any clinical disease states. (Footnote Continued) "Polychlorinated Biphenyls, Dibenzofurans, and Quarterphenyls in the Toxic Rice-Bran Oil and PCBs in the Blood of Patients with PCB Poisoning in Japan," 5 Amer. J. Ind. Med. 133 (1984); Kashimoto, et al., "Role of Polychlorianted Dibenzofuran in Yusho (PCB Poisoning)," 36 Arch. Environ. Health 321 (1981); Masuda and Yoshimura, "Polychlorianted Biphenyls and Dibenzofurans in Patients with Yusho and Their Toxicological Significance," 5 Amer. J. Ind. Med. 31 (1984); and Kunita, et al., "Causal Agents of Yusho, " 5 Amer. J. Ind. Med. 45 (1984). 2/ Brown, D. P., and M. Jones, "Mortality and Industrial Hygiene Study of Workers Exposed to Polychlorinated Biphenyls," 36 Arch. Environ. Health 120-29 (1981); Bertazzi, P. A. , et al., "Mortality Study of Male and Female Workers exposed to PCBs," Paper presented at the International Symposium on Prevention of Occupational Cancer (April 21-24, 1981, Helsinki, Finland). 3/ Lawton, R. W. , ^t al., "Studies of Employees Occupationally Exposed to PCBs," General Electric Progress Report (1981). PCB-ARCH-EXT0371864 -4- The reference in EPA's Health Advisory draft on PCBs (at page 4) to an increase in incidence of malignant melanoma in petrochemical workers exposed to PCBs and other identified chemicals should be afforded no weight. This study 4/ is not adequate to reach conclusions of an associa tion with carcinogenicity due to the small number of indi viduals exposed and the confounding variable of exposure in the workplace to many other chemicals. Indeed, the study was subsequently withdrawn for revision and has not been reissued. 5/ In sum, substantial human data indicate even heavily exposed workers have not developed serious clinical diseases attributable to PCBs. No significant human evidence of PCB association with any cancer exists. B. Contrary to EPA's Discussion, All PCBs Have Been Found to Be Non-Mutagenic._ There is also no significant evidence that PCBs are mutagenic in test systems or in human populations. It is thus quite unlikely that PCBs would exert mutagenic activity 4/ Bahn, A. K. , et al. , "PCBs and Melanoma," 296 New England J. Med. 108 (1977); Bahn, A. K., et al., "Melanoma After Exposure to PCBs," 295 New England J. Med. 450 (1976). 5/ See NIOSH 1977 Criteria for a Recommended Standard: Occupational Exposure to Polychlorinated Biphenyls (PCBs), USDHEW, NIOSH Publication No. 77-225. PCB-ARCH-EXT0371865 -5 in humans. This conclusion is consistent with the lack of excess cancer incidence observed in PCB-exposed human popu lations. EPA's reference to a mutagenicity assay of 4-chlorobiphenyl as being positive, 50 Fed. Reg. at 47002, is inaccurate. That stud; ' contradicted by numerous other mutagenicity assays of P 6/ More significantly, the co-author of that study has, since its initial release. 6/ McMahon, et al., "Assay 855 Test Chemicals in Ten Tester Strains Using a New Modification of the Ames Test for Bacterial Mutagens," 39 Cancer Res. 682 (1979); Environmental Protection Agency, "Ambient Water Quality Criteria for Polychlorinated Biphenyls," EPA 440/5-80-068 PB 81-117798 (1980); Bruce and Heddle, "The Mutagenic Activity of 61 Agents as Determined by the Micronucleus, Salmonella and Sperm Abnormality Assays," 21 Can. J. Genet. Cytol. 319 (1979); Schoeny, et al., "Non-mutagenicity for Salmonella of the Chlorinated Hydrocarbons Aroclor 1254, 1,2,4-trichlorobenzene, mirex and kepone," 68 Mutat. Res. 125 (1979); and, Rinkus and Legator, "Chemical Characterization of 465 Known or Suspected Carcinogens and Their correlation with Mutagenic Activity in the Salmonella Typhimurium System," 39 Cancer Res. 3289 (1979). Other studies that support the lack of mutagenic activity for PCBs include an absence of effects in the micronucleus test and sperm morphology tests. (Bruce and Heddle (1979) previously cited; Jensen and Ramel, "The Micronucleus Test as Part of a Short-Term Mutagenicity Test Program for the Prediction of Carcinogenicity Evaluated by 143 Agents Tested," 75 Mutat. Res. 191 (1980). Others have shown that PCBs did not produce chromosomal damage in the testes and bone marrow of rats (Dikshith, et al., "Effect of Polychlorinated Biphenyl (Aroclor 1254) on Rat Testes," 22 Exp. Mol. Path. 376 (1975); and, Garthoff, et al., "Biochemical and Cytogenetic Effects in Rats Caused by Short-Term Ingestion of Aroclor 1254 or Firemaster BP6," 3 Toxicol. Environ. Health 769 (1977). PCB-ARCH-EXT0371866 -6- indicated that he had been unable to replicate the result and that it was his belief that PCBs should not be consid ered mutagenic. 7/ In sum, no prediction of PCB carcinogenicity can be based on any mutagenicity results. C. The Inconsistent Bioassay Results Show No More Than Limited, Inconclusive Evidence of Animal Carcinogenicity. EPA's placement of PCBs in Category I based upon strength of evidence of carcinogenicity is inappropriate. The existing data do not provide "sufficient human or animal evidence of carcinogenicity" to warrant the regulation of PCBs "as probably human carcinogens." 50 Fed. Reg. at 46948. To the contrary, the only possible evidence indi cating carcinogenic risk is in the animal data and that data should place PCBs in Category III as it is "inadequate" evi dence of carcinogenicity. _Id. At a minimum, PCBs should be placed in Category II given that the evidence is "limited inconclusive evidence . .. from animal data." Id. A sizeable volume of animal experimental work has been directed toward chronic studies of PCBs in several species: the mouse, the rat, and the dog. The data shows: (a) the 7/ See Affidavit of Dr. Steven Safe submitted to EPA in 1980 by the Dow Chemical Company. A copy of that affidavit is attached as Appendix A to these comments. PCB-ARCH-EXT0371867 7- evidence on carcinogenicity is negative for gastrointestinal carcinoma and bladder carcinoma in rats and hepatocellular carcinoma in the dog; and (b) some studies have reported an increase in hepatocellular carcinoma in mice and rats ex posed to commercial PCBs, whereas other studies have afford ed negative results. 8/ Animal studies thus do not provide convincing evidence that PCBs induce liver cancer. Of the major studies in the rat, one has been judged positive and two have been nega tive. Hepatic carcinoma was not produced in the dog. Chronic administration of Aroclors in the rat did not induce bladder cancer, gastrointestinal carcinomas, or cancer of 8/ See, Ito, N., et al., "Histopathologic Studies on Liver Tumorigenesis Induced in Mice by Technical Polychlorinated Biphenyls and Its Promoting Effect on Liver Tumors Induced by Benzene Hexachloride," 51 J. Natl. Cancer Inst. 1637 (1973); Kimbrough, R. D. and R. E. Linder, "Induction of Adenofibrosis and Hepatomas of the Liver in BALB/cJ Mice by Polychlorinated Biphenyls (Aroclor 1254)," 53(2) J. Natl. Cancer Inst. 547-52 (1974); Kimbrough, R. D., ^t al., "Induction of Liver Tumors in Sherman Strain Female Rats by Polychlorinated Biphenyl (Aroclor 1260)," 55 J. Natl. Cancer Inst. 1453-59 (1975); Calandra, J. C., "Summary of ~~ Toxicological Studies on Commercial PCBs," Proc. of the National Conference on Polychlorinated Biphenyls Chicago, 111. (Nov. 19-21, 1975); Calandra, J~. C., "Summary of Toxicological Studies on Commercial PCBs," Proc. of the National Conference on Polychlorinated Biphenyls 35-42 (EPA-560/6-75-004) (1976); National Cancer Institute, Bioassay of Aroclor 1254 for Possible Carcinogenicity, No. 38, NEW (1978); Preston, B. D., et al., "Promoting Effects of Polychlorinated Biphenyls (Aroclor 1254) and Polychlorinated Dibenzofuran-free Aroclor 1254 on Diethyl-Nitrosamine-Induced Tumorigenesis in the Rat," 66(3) J. Natl. Cancer Inst. 509-25 (1981). PCB-ARCH-EXT0371868 -8- the thyroid gland, pituitary gland, adrenal gland, uterus, lung, hematopoietic system, or other organs. Much of the controversy surrounding this issue involves interpretation of the significance of hepatocellular prolif erative lesions noted in some but not all chronic studies. The liver is a target organ for PCBs. Chronic administra tion of sufficiently high levels of PCBs can induce liver injury in animals leading to a proliferative response in hepatic tissue. This response may be reparative in nature and not due to genotoxic interactions, since the -^majority of short-term assays demonstrate that PCBs are not mutagenic. Based on these considerations, exposure to moderate environ mental levels of PCBs would not pose a significant carcinogenic risk to man. In sum, EPA errs by concluding that PCBs are a probable human carcinogen. There is "inadequate" evidence of carcinogenicity to reach such a conclusion. At best, PCBs should be placed in SDWA Category II given the "limited in conclusive evidence ... from animal data." Accordingly, consistent with RMCLs proposed for other substances at this time, a numerical number other than zero should be estab lished as the RMCL for PCBs. PCB-ARCH-EXT0371869 -9- II. UNJUSTIFIED EXPENDITURE OF SOCIETAL RESOURCES WOULD BE MANDATED BY ESTABLISHMENT OF A ZERO RMCL FOR PCBs. Should EPA adopt an RMCL of zero for PCBs, it will be required to fashion a Maximum Contaminant Level (MCL) for PCBs that will, in turn, require either monitoring and/or treatment of all drinking water in this country for this substance. As PCBs can be expected to be found in most drinking water supplies only at very low levels, it would be inappropriate to initiate this regulatory action based on an RMCL of zero that will require inevitably much monitoring throughout the country. Much more appropriate, given the limited inconclusive evidence of carcinogenicity, would be determination at this time of a reasonable limit for a PCB RMCL. CMA thus urges that the RMCL for PCBs not be zero. To the extent the Agency feels a need to establish any RMCL, an appropriate basis for such a value would be in FDA's conclu sion that the tolerance for PCBs in the diet should be 13 micrograms per day. The Food and Drug Administration has set a tolerance limit of 2 ppm PCBs in (21 C.F.R. Part 109). Assuming an average person's daily consumption of PCBs in fish is 6.5 vg/day, the average daily consumption of PCBs g. 1^'fi PCB-ARCH-EXT0371870 -10- would be 13 vg/day. Accordingly, given average human con sumption of 2 liters of water per day, the RMCL would be 6.5 yg/liter. . CONCLUSION. ' CMA urges that an RMCL for PCBs be established at at least 6.5 yg/liter. Such an RMCL would be more than ade quately protective of the nation's drinking water supplies and would more accurately reflect the substantial epidemi ologic and toxicologic information on this substance. PCB-ARCH-EXT0371871