out, the Food & Drug Act "does not apply that Draconian approach to drugs." OSHA goes about its regulation of carcinogens in another way. Morgan says that OSHA's first efforts in this area involved "asbestos, a known human carcinogen, and OSHA's regulation limited employee exposure to the extent technologically feasible, but did not ban use of the material or adopt a zero-exposure standard." In a rule-making on a group of 14 chemicals, Morgan says that OSHA "adopted limitations that it regarded as technologically feasible." * And in 1974 OSHA issued regulations for another human carcinogen, vinyl chloride, and imposed exposure restrictions based upon technological capabilities. EPA in its dealings with vinyl chloride issued a proposal of a "technology forcing" nature, but which would not completely ban emissions of the chemical. How EPA would deal with real or potential chemical carcinogens under pending toxic substances control legislation remains to be seen. Congress has yet to complete action on the legislation. However, Morgan points out, under the Senate version, a chemical poses an "unreasonable risk" and can be regulated if EPA determines that at the level of human exposure and with appropriate safety margins the chemical has the "potential" of inducing "cancer" in humans. Such a determination can be made on the basis of animal testing, he says, adding that the bill gives the highest priority to testing and control of chemicals that have the "potential" for causing "cancer." However, the legislation contains "no criteria for assessing carcinogenic risks and virtually no limits on the restrictions that EPA may impose." Criteria do exist after a fashion in a potpourri of "principles" introduced into the administrative proceedings by EPA officials in seeking to suspend or cancel registrations of the pesticides aldrin/ dieldrin, chlordane and heptachlor, and mirex. Morgan points out that in a number of these proceedings "EPA officials have endorsed the view that evidence of tumor production in a single animal species warrants regulation of a pesticide as a human carcinogen.... Other principles reject dose-response theories and threshold limits on the ground that they could not be established," he says. SOCMA seminar participants collectively seemed to take an altogether dim view of EPA's various listings of principles for assessing chemical Carcinogenicity, labeling the principles scientifically unsound, among other things. However, EPA, after more than a little internal controversy over the principles between the agency's lawyers and scientific contingent, is itself reassessing its approach toward regulating chemicals including the question of chemical carcinogenicity. Last October EPA administrator Russell Train ordered two task groups set up. One group was to develop procedures for evaluating and describing risks and subsequently to review the health aspects of all cancer decisions in the agency, and a second
group was to develop procedures for an economic risk-benefit sort of analysis. How soon these groups will issue reports isn't clear, but agency officials indicate that it is only a matter of weeks. Also only a matter of weeks away— indeed, a final draft was being worked over at press time—are general criteria for assessing carcinogenicity of chemical substances put together by a Subcommittee on Environmental Carcinogenesis of the National Cancer Advisory Board at the National Cancer Institute (C&EN, March 15, page 7). Judging from coffeebreak conversations at the SOCMA seminar, the chemical industry looks with much more favor on what the NCI panel may produce than it does the "principles" used by EPA so far in pesticide proceedings. In any event, it is apparently up to NCI head Frank Rauscher to decide to issue under the imprimatur of NCI whatever the environmental carcinogenesis panel puts in its final report. The most recent "final draft" points out that the subcommittee "clearly recognized that at the present time there is no simple and universal definition of either carcinogenesis or neoplasia. The criteria which are described should, therefore, be considered as general guidelines and not rigid, universal criteria. The complexity of the problem dictates that in the final analysis, the evaluation of the potential human hazards of a given agent must be individualized in terms of the chemical(s) and metabolic aspects of that agent, its intended use(s), the data available at the time that the decision must be made, and other factors pertinent to the case under consideration. Each case must be considered on its own, and the criteria appropriate for one agent may not necessarily apply to another." Discussions of real or potential federal regulatory actions against chemicals aside, the SOCMA seminar focused on a potpourri of more technical discussions on chemical carcinogenicity. Topics ranged from immunology to the role of experimentation and epidemiology in the assessment of industrial cancer hazards to quantifying risks from exposures to chemical carcinogens to management of occupational and environmental problems at Du Pont. Finally, the SOCMA seminar provided participants with a somewhat less than upbeat outlook for the chemical industry in its public image. In a luncheon address, Nye Stephens, vice president, Yankelovich Skelly & White Inc., indicated that the chemical industry faces some tough image problems in the days ahead—not only in the eye of the public at large but also in the eye of key governmental and other decision makers. This in large measure, he indicates, is a result of the chemical industry's being increasingly identified as a particular villain in worker safety, as a manufacturer of unsafe products, and as an increasing contributor to the nation's air and water pollution and solid waste problems. Fred H. Zerkel, C&EN Washington
EPA starts pesticide reregistering program The Environmental Protection Agency has plunged into the arduous task of reregistering some 29,000 currently approved pesticides by October 1977. The agency recently has issued regulations governing the program, started to call in the first batch of pesticides for ^registration, and is searching its files to determine what data still are needed to support reregistration of the products. So far EPA has discovered that the registration of more than half of the pesticides' active ingredients is not supported by adequate safety and health data. The agricultural chemical industry, although not exactly jumping for joy because of the tremendous amount of work involved in the program, apparently is taking a wait-and-see attitude toward it. The industry seems to have accepted the program as a fact of life and as something that might as well be gotten out of the way as soon as possible, though there are fears that substantial problems may develop as the program gets into full swing. A full formal evaluation of each use of each pesticide would be, according to EPA administrator Russell E. Train, "extremely costly to perform and practically impossible in the light of administrative constraints." To whittle the program down to a more manageable size EPA is concentrating its reregistration efforts on making sure that the roughly 1500 active ingredients used in various pesticide formulations meet current safety data requirements. EPA is not requiring, at this time, environmental chemistry and efficacy data on the ingredients. These data will be required for future five-year renewals of pesticide registrations. The safety data required for reregistration include toxicity data needed for determining the acute oral LD50 (lethal dose in 50% of the animals tested) of the ingredient for mammalian species, the subacute LC50 (lethal concentration in 50% of the animals tested) for avian species, and the acute LC50 for aquatic organisms, unless use patterns of the ingredients would not result in exposure to birds and fish. If use of the ingredients can be expected to leave even very low residues on foodstuffs, 36-month oral and dermal animal studies are required to determine a substance's oncogenic (tumor producing) potential, as well as 36-month chronic feeding studies and 24-month reproductive studies. Oncogenic studies also will be required if the active ingredient, its metabolite, or degradation product contains a substance structurally related to a known or suspected oncogenic agent. Teratogenicity data are required if use of the active ingredient may be reasonably expected to result in exposure to human females. EPA is assigning each active ingredient to one of five categories depending on how much data still are needed to support reregistration. An active ingredient is assigned to category I if all data necessary March 22, 1976 C&EN
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to support reregistration already are in EPA's hands. In category II are those active ingredients for which long-term testing data, such as teratogenicity and chronic feeding studies, are lacking. These ingredients will be given a conditional reregistration for a period long enough to allow development of the data and submission of them to EPA. In category III are those ingredients for which short-term testing data, such as acute oral and dermal toxicity studies, are lacking. Under the regulations these tests must be completed before reregistration can be obtained. If the data are not submitted within six months of notification, registration of all products containing the active ingredient will be subject to cancellation. In category IV will be those ingredients that show prima facie evidence of posing a potential unreasonable risk to human health or the environment. Category V is a catchall category for ingredients that have not yet been assigned to another category. EPA is combing its files to determine which active ingredient to put in which category. The results of the search to date appear to support charges made last month by both the General Accounting Office and three lawyers who resigned in protest from EPA's general counsel's office that the data underlying the registration of a substantial number of widely used pesticides are not supported by adequate safety data (C&EN, Feb. 16, page
19). Of the 650 ingredients that EPA has so far categorized only 180 are supported by enough evidence to allow reregistration, 442 or 62% require further long-term testing, and 28 require further short-term testing. About 850 active ingredients are still awaiting classification and are now included in category V. EPA has not officially assigned any ingredients to category IV. But EPA finds that a first check of its files has revealed 102 ingredients, which, based on existing registration data, unverified studies that have appeared in the scientific literature, or a chemical similarity to canceled pesticide products, are candidates for inclusion in that category. An ingredient is included in category IV because of indications that it may cause cancer, is embryotoxic, or because its use would cause a population reduction in nontarget organisms or fatality to endangered species. In releasing the list of the 102 ingredients to the House Subcommittee on Conservation, Energy & Natural Resources, which had requested it, Train emphasized the very tenuous nature of the list so far. He pointed out that the screening mechanism employed by EPA can give rise only to a presumption of unreasonable risk, not a final determination. He said that, if after an extensive scientific review of the data that had led to the ingredients' safety being questioned, there is still reason to believe that
they pose an unreasonable risk, registrants, users, and the general public still can rebut the presumption. They will be given every opportunity to demonstrate that the risk is not as substantial as originally presumed, that it may be reduced through labeling and other use restrictions, or that the benefits of the ingredient outweigh the risk involved and thus the products containing the ingredient should be reregistered. For once an EPA program is not drawing howls of protest from the affected industry. As one agricultural chemical industry spokesman puts it, the reregistration program is, for better or worse, relatively straightforward. And he says that although it is hard to see how either EPA or the industry can get the job done by the October 1977 deadline, everyone is going to do his or her best to accomplish it. So far, he says, toxicology testing laboratories have indicated that they will be able to perform the necessary long-term testing. But this situation may very well change if many more ingredients are included in category II. The biggest concern appears to be that because of the difficult and complex task EPA is involved in in identifying and validating all the data that have been submitted over the years for the reregistration program, the registration process for new pesticide products may very well grind to a halt until the reregistration program is completed. Janice R. Long, C&EN Washington
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C&EN March 22, 1976
