Regulating environmental carcinogens Dear Sir: Kocher and Hoffman (ES&T, Dec. 1991, p. 1986) review the risk assessment considerations and underlying regulatory consequences as regards acceptable levels of radionuclides and chemical carcinogens. Mathematical formulations are utilized to determine acceptable levels of exposure, and new concepts are defined as “as low as reasonably achievable” (ALARA). A key problem with the presentation of Kocher and Hoffman is that it neglects the distinct classes of carcinogens with specific mechanisms of action, that must be taken into account for realistic risk assessment. Indeed, chemical carcinogens have been classified into two types. The first class is genotoxic, that can change cellular macromolecules, including DNA ( 2 - 4 ) . This reaction leads to a mutational event by activation of oncogenes and associated reactions, or altering tumor suppressor genes. Most chemicals documented to cause cancer in humans are genotoxic ( 2 , 5). Complex factors like tobacco and smoking, or nutritional traditions include genotoxic carcinogens (6, 7). There are excellent rapid bioassay techniques to determine w h e t h e r or not a chemical is genotoxic (8). For genotoxic carcinogens, the customary risk assessment techniques utilize theoretically a linear extrapolation without threshold (9, 2 0 ) . However, even with such chemicals, there may be practical no-effect levels. This is important, since modern chemical analytical techniques can reliably measure vanishingly s m a l l , toxicologically insignificant amounts. Yet, conservative, public health interpretation suggests that the ALARA concept (see Kocher and Hoffman) be applied to risk assessment with genotoxic carcinogens. A second class of carcinogens involves chemicals that are not genotoxic in appropriate tests but have caused cancer in animal models through promotion. There are specific tests to detect potential promoting activity in agents with such attributes ( 4 , 2 2 - 2 3 ) . Many environmental chemicals s u c h as those found in chemical waste dumpsPCBs, dioxins, chloroform, perchlo-
roethylene, or other halogenated hydrocarbons-have been conclusively shown to be negative in tests for genotoxicity. They have caused liver cancer in mice, most likely by a promoting process since the mice used have a gene structure with activated oncogenes (24). The procedures of Kocher and Hoffman do not apply to such nongenotoxic carcinogens. Risk versus dose can be defined by the customary pharmacologic S-shaped doseresponse curve with a threshold. The mechanism of action of promoters involves an effect on cell cycling, cytotoxicity, or promotion, but does not lead to permanent imprinting or alteration of the genome ( 4 , 25). For that reason, their effect is reversible u p o n reduction o r elimination of exposure. Ultrasensitive, precise analytical results have led to scientifically unwarranted claims of human cancer risk with such nongenotoxic carcinogens. Ths main etiologic factors for the m a i n h u m a n c a n c e r s are w e l l known, namely, lifestyles involving the use of tobacco, and undesirable dietary traditions too high in fat and salt a n d too low i n vegetables, fruits, fiber, and essential micronutrients (6, 16, 17). The public may not be willing to adjust their lifestyles to a real lower risk situation, if unwarranted cancer claims (“everything causes cancer” is the fatalistic public reaction) are made for trace amounts of environmental chemicals operating by nongenotoxic mechanisms.
References (1) Clayson, D. B.; Clegg, D. J. Regulatory Toxicol. Pharmacol. 1991, 1 4 , 1 4 7-66.
(2) Ames, B. N.; Gold, L. S. In Xenobiot-
(3) (4)
(5)
(6)
ics and Cancer: Ernster, L. et al., Eds.; Japan Science Society Press: Tokyo, 1991; pp. 303-14. Singer, 8 . ; Essigmann, J. M. Carcinogenesis 1991, 12, 949-55. Williams, G. M.; Weisburger, J, H. In Casarett and Doull’s Toxicology, 4th ed.; Amdur, M. 0.;Doull, 7.; Klaassen, C. D., Eds.; Pergamon Press: New York, 1991; pp. 127-200. International Agency for Research on Cancer. IARC Monographs on Evaluation of Carcinogenic Risks to Humans (serial); IARC: Lyon, France. Hoffmann, D.; Hecht, S. S. In Chemical Carcinogenesis and Mutagenesis I; Cooper, C. S.; Grover, P. L., Eds.; Springer-Verlag: New York, 1990, pp. 61-102.
001 3-936X/92/0926-845$03.00/0 G 1992 American Chemical Society
(7) Sugimura, T. et al. In Xenobiotics and
Cancer: Ernster K. et al., Eds.; Japan Science Society Press: Tokyo, 1991; pp. 279-88. (8) Williams, G. M. A n n u . Rev. Pharmacol. Toxicol. 1989, 29, 189-211. (9) Morris, S. C. Cancer Risk Assessment: A Quantitative Approach; Marcel Dekker, Inc.: New York, 1990, pp. 3-408. (10) Office of Technology Assessment. Congress of the United States; Identif y i n g and Regulating Carcinogens; Marcel Dekker: New York and Basel, 1989, pp. 3-249. (11) Dragan, Y. P. et al. Fundam. A p p l . Toxicol. 1991, 16, 525-47. ( 1 2 ) Krutovskikh. V. A.: Oyamada, M.; Yamasaki, H. Carcinogenesis, 1991, 12, 1701-06. (13) Trosko, J. E.; Chang, C. C. In Banbury Reporf 31, Carcinogen Risk Assessment: N e w Directions in the Qualitative and Quantitative Aspects; Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY, 1988; pp. 139-70. (14) Goodman, J. I. et al. Fundam. Appl. Toxicol. 1991, 17, 651-65. [15) Cohen, S. M.; Ellwein, L. B. Science 1990, 249,1007-11. (16) Taioli, E.; Nicolosi, A,; Wynder, E. L. Nutr. Cancer 1991, 16, 259-65. (17) Weisburger, J. H.; Horn, C. L. American Cancer Society Textbook on Clinical Oncology, 6th ed.; Holleb, A,; Fink, D., Eds.; American Cancer Socie t y Atlanta, GA, 1991; pp. 80-98.
JohnH. Weisburger American Health Foundation Valhalla, NY 10595
The authors reply: We would like to respond to the letter by J. H. Weisburger concerning our paper on regulating environmental carcinogens. From several comments in his letter, he apparently has misunderstood the purpose and scope of our paper and, thus, has fundamentally misrepresented our work. The misrepresentation of our work is indicated by the statements that: (a) we “review the risk assessment considerations” regarding environmental carcinogens (first paragraph, first sentence); (b) “a key problem with [ourl presentation. , . is that it neglects the , , . distinct classes of carcinogens . . , that must be taken into account for realistic risk assessment (second paragraph); and (c) [our] procedures do not apply to . . nongenotoxic carcinogens’’ (sixth paragraph, first sentence). Each of these statements implies, incorrectly, that our paper is conI
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cerned with models or procedures for assessing risks from exposure to environmental carcinogens. On the contrary, our paper is not concerned with risk assessment. Rather, it is concerned only with regulation (control) of risk. That is, our p a p e r lays o u t a p r o p o s e d framework by which regulatory authorities, given estimates of risk from exposure to any environmental carcinogens, would decide on appropriate actions to reduce risks to the public. Our proposal does not depend in any way on methods for assessing risk. To be sure, we support the use of scientifically valid methods for risk assessment, but our proposal accommodates any methods or assumptions for estimating carcinogenic risk, be they valid or not. Weisburger apparently has not understood the distinction between assessing and regulating (controlling) risk. Thus, it would be more appropriate to direct his comments at agencies, such as EPA, which develop policies for risk assessment. We would also comment briefly on three other points. First, Weisburger asserts that we utilize “mathematical formulations . . , to determine acceptable levels of exposure” (first paragraph, second sentence). We are not sure what this means, b u t w e d i d not use any kind of mathematical model to determine acceptable levels of exposure (risk). All we did is propose levels of d e manifestis a n d d e m i n i m i s risks based primarily on considerations of regulatory precedents and, secondarily, on estimated risks from naturally occurring carcinogens. Thus, the risk levels defining our proposed regulatory framework represent subjective judgments, not determinations using mathematical formulations. Second, in this same sentence. Weisburger refers to “as low as reasonably achievable (ALARA)” as a “newer concept.” Again, we are not sure what this means, but we note that the ALARA concept has been a fundamental aspect of radiation protection principles for nearly 40 years ( 2 ) and was often applied in radiation protection practices long before then ( 2 ) .Perhaps explicit recognition of the ALARA concept is relatively new in regard to protection principles for other carcinogens. Finally, in the fourth paragraph, Weisburger appears to question use of the ALARA concept when there may be a “practical” threshold for effects from genotoxic carcinogens. 846
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We presume that “practical noeffect levels” refer to risks that would be too low to be observed and associated with exposures in an epidemiological study. We hope this will be the case for almost all exposures to environmental carcinogens. However, it is surely proper for regulatory authorities to take action towards risk (exposure) reduction at levels below which effects would be observed, and use of the ALARA concept for this purpose is reasonable.
References (1) “Permissible Dose from External
Sources of Ionizing Radiation”; National Council on Radiation Protection and Measurements: IVashington, DC, 1954; Report No. 1 7 . (2) Taylor, L. S . Health Phys. 1981, 4 2 , 227-32.
Based on work performed at Oak Ridge National Laboratory, managed for the U.S. Department of Energy under contract DE-AC05-840R21400 with Martin Marietta Energy Systems, Inc.
David C. Kocher Health and Safety Research Division Oak Ridge National Laboratory Oak Ridge, TN 37831 F. Owen Hoffman Environmental Sciences Division Oak Ridge National Laboratory Oak Ridge, TN 37831
Nuclear power plants Dear Sir: In ES&T (Oct. 1991, p. 1682), Alan Newman reported on “An International View of Nuclear Power Plants.” The article is summarized by ESGT as: “Nuclear power is viewed worldwide as a viable technology.” In my view, this article gives an incorrect perspective of the situation. Large parts of the public in Europe, as well as a number of governm e n t s , are u n w i l l i n g to accept enlargement of nuclear capacity in their countries. This can be illustrated by comparing a quotation from the ES&T article with corresponding quotations from the recent overview of the International Energy Agency (IEA) on Climate Change Policy Initiatives, update of 20 November 1991. Newman writes: “Despite the opposition of groups like Greenpeace, public opinion in European countries seems to favor nuclear power. In 1990 Swiss voters rejected an initiative to close down that country’s five nuclear power plants, and this year Sweden’s Parliament abandoned a 1988 decision to decommission two nuclear plants in 1995-96.”
The IEA in their document on Switzerland mentioned that: “In the referendum in September 1990, a ten-year (and in fact even longer) moratorium regarding the licensing of new nuclear production facilities was approved. However, a gradual phase-out of nuclear energy was rejected. According to the federal government, the construction of fossilfueled power plants or additional long-term contracts for electricity imports should be avoided. Priority is therefore given to the efficient use of energy, including electricity. After the turn of the century, the question whether to renew, extend, or phase-out nuclear capacities will arise again.” The IEA document on Sweden mentioned: “In February 1991, the Energy Policy Bill, based on the inter-party agreement [i.e., between the Social Democrats, the Liberal Party, and the Center Party] was presented to Parliament. According to the agreement, the time at which the nuclear phase-out can begin and the rate at which it will proceed, will depend on the results of electricity conservation measures, on the supply of electricity from environmentally acceptable sources and on whether internationally competitive electricity prices can be maintained. The 1980 parliamentary decision to phase-out nuclear power by 2010 has not been reconsidered.” Clearly, the decisions to keep open existing nuclear power plants are taken against a background of severe distrust on nuclear power. Similar examples could be given from other parts of Europe. In a more objective article on the status a n d prospects of nuclear power, ES&T might further have mentioned that the Japanese government has been unable to secure so far the necessary new sites for nuclear power plants due to resistance at local levels, that the government of the United Kingdom was unable to sell its nuclear power plants to private investors. and that Germany provides some examples of “economic catastrophes” in the nuclear field, e.g., at Kalkar. Finally, I wish that at least the reports on nuclear power could be trusted. Jacob Swager Head o f the Climate Change Division Ministry of Housing, Physical Planning and Environment of the Netherlands Postbus 450 2260 MB Leidschendam The Netherlands
