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TELEPHONE HUDSON 3-6126 Manufacturing Chemists' Association, Inc. (FOUNDED 1S721 1825 Connecticut Avenue, N. W, Washington, D. C. 20009 August 21, 1967 TO: Members of the Food, Drug, and Cosmetic Chemicals Committee SUBJECT: Report of the Panel on Potentiation of the FDA Advisory Committee \ Gentlemen: At the June 13 meeting of the FDCC Committee, 1 was ashed to obtain the subject report dated March 16, 1967 for your information. Enclosed is a copy. Sincerely yours, MMB:sjg Enclosure Morgan M. Hoover ASI 00002118 FOOD AND DRUG ADMINISTRATION ADVISORY COMMITTEE ON PROTOCOLS FOR SAFETY EVALUATIONS Report of tin Panel on Potentiation on Testing for Potentiation between Anticholinesterase Pesticides March 16, 1067 Committoe Members: Norton Nelson, Chairman Julius M. Coon ' Loo Friedman Robert E. Gossc!.in Calvin M. Kunin Tod A. Loomis Philippe Shubik James L. Whittcnbeigor James 0. Wilson Panel onPotentiation Members: Julius 11. Coon, Chairman Kenneth P. PtOois (consultant) John P. Frawley (consultant) Robert E. Gosselin Tod A, Loom!s FTA Liaison Representative to the Panel on Potentiation; Joseph L. Svirbely Executive Secretary:. Charles J, Kokoski ASI 00002119 Report: of the Panel on P tentlation on Testing for Potentiation between Anticholinesterase Pesticides In 1957, it was found that EPN exerted a narked potentiation of the toxicity of malathlon under certain experimental conditions. Since that time numerous exatnplos of important toxicological interactions have come to light, not only between other anticholinesterase pesticides, but also between these agents and other environmental chemicals, as well as drugs. There has been a continuing and growing concern about these toxicological interactions. This panel was assigned the specific task of considering the usefulness of the FDA requirement (F.R. par. 120.35) that each new anticholinesterase pesticide be tested for toxicity In combination with each of the other anticholinesterase pesticides for which a tolerance has been set. In > regard to this requirement and the design of the tests that have been run to meet it,this panel has two recommendations to make: 1. The present requirement as set forth in the Federal Regulations (par, 120.35) should be abandoned since it has failed to serve any useful purpose. This recommendation is based on two considerations. Firstly, no single, practical experimental design has been developed by which it is possiblo to detect all cases of potentiation between pairs of anticholinesterase pesticides. Secondly, even in cases where the current test procedure has shown the existence of potentiation, the results do not supply Information pertinent to the safety evaluation of pesticide residues on agricultural conmodltfes. None of the established potentiative pairs, when fed subacutoly to experimental animals at or near the minimal effect levels, has shown ASI 00002120 -3establish the optimal procedur Cor detecting anti-allesterase activity. In the meantime, the panel urges the FDA to accumulate data that would contribute to our knowledge of the general toxicologic and physiologic significance of the aliesterases. March 16, 1967 Dr. J. L. Svirbely (FDA Represent;tive) Dr. K. P. DuBois (consultant) Dr. J. P. Frawley (consultant) Dr. R. E. Gosselin Dr. T, A. Loomis Dr. J. H. Coon (chairman) ASI 00002122