© 1998 Oxford University Press
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Common Mechanism of Toxicity: A Case Study of Organophosphorus Pesticides
1ILSI Risk Science Institute 2Mississippi State University 3DowElanco 4Vanderbilt University 5VA-MD Regional College of Veterinary Medicine 6University of Maryland School of Medicine 7National Center for Toxicological Research FDA 8U.S. Environmental Protection Agency, OPP 9North Carolina State University 10Hines VA Hospital & Loyola University Medical Center 11U.S. Environmental Protection Agency, NHEERL 12Northeast Louisiana University 13University of Michigan 14Technology Services Group 15Department of Toxicology, Bayer Corporation 16UMD New Jersey Medical School 17University of Minnesota School of Medicine
Received December 15, 1997; accepted January 16, 1998
The Food Quality Protection Act of 1996 (FQPA) requires the EPA to consider "available information concerning the cumulative effects of such residues and other substances that have a common mechanism of toxicity ... in establishing, modifying, leaving in effect, or revoking a tolerance for a pesticide chemical residue." This directive raises a number of scientific questions to be answered before the FQPA can be implemented. Among these questions is: What constitutes a common mechanism of toxicity? The ILSI Risk Science Institute (RSI) convened a group of experts to examine this and other scientific questions using the organophosphorus (OP) pesticides as the case study. OP pesticides share some characteristics attributed to compounds that act by a common mechanism, but produce a variety of clinical signs of toxicity not identical for all OP pesticides. The Working Group generated a testable hypothesis, anticholinesterase OP pesticides act by a common mechanism of toxicity, and generated alternative hypotheses that, if true, would cause rejection of the initial hypothesis and provide criteria for subgrouping OP compounds. Some of the alternate hypotheses were rejected outright and the rest were not supported by adequate data. The Working Group concluded that OP pesticides act by a common mechanism of toxicity if they inhibit acetylcholinesterase by phosphorylation and elicit any spectrum of cholinergic effects. An approach similar to that developed for OP pesticides could be used to determine if other classes or groups of pesticides that share structural and toxico-logical characteristics act by a common mechanism of toxicity or by distinct mechanisms.
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