Common mechanism of toxicity: a case study of organophosphorus pesticides.
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 alternative 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 toxicological characteristics act by a common mechanism of toxicity or by distinct mechanisms.
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Related Subject Headings
- Toxicology
- Risk Assessment
- Organophosphorus Compounds
- Insecticides
- Humans
- Drug Interactions
- Cholinesterase Inhibitors
- Animals
- 3214 Pharmacology and pharmaceutical sciences
- 1115 Pharmacology and Pharmaceutical Sciences
Citation
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Toxicology
- Risk Assessment
- Organophosphorus Compounds
- Insecticides
- Humans
- Drug Interactions
- Cholinesterase Inhibitors
- Animals
- 3214 Pharmacology and pharmaceutical sciences
- 1115 Pharmacology and Pharmaceutical Sciences