Neurotoxicity resulting from coexposure to pyridostigmine bromide, deet, and permethrin: implications of Gulf War chemical exposures.

摘要: Of the three-quarters of a million service personnel involved in Persian Gulf War, approximately 30,000 have complained neurological symptoms unknown etiology. One contributing factor to emergence such may be simultaneous exposure multiple agents used protect health personnel, particular, anti-nerve agent pyridostigmine bromide (PB; 3-dimethylaminocarbonyloxy-N-methylpyridinium bromide), insect repellent DEET (N,N-diethyl-m-toluamide), and insecticide permethrin (3-(2,2-dichloro-ethenyl)-2,2-dimethylcyclopropanecarboxylic acid (3-phenoxyphenyl)methyl ester). This study investigated neurotoxicity produced hens by individual or these (5 d/wk for 2 months 5 mg/kg/d PB water, po; 500 DEET, neat, sc; corn oil, sc). At dosages, single compounds resulted minimal toxicity. Combinations two greater than that caused agents. Neurotoxicity was further enhanced following concurrent administration all three We hypothesize competition liver plasma esterases leads their decreased breakdown increased transport parent compound nervous tissues. Thus, carbamylation peripheral reduces hydrolysis increases availability system. In effect, "pumps" more into central Consistent with this hypothesis, exposed combination exhibited neuropathological lesions several characteristics similar those previously reported studies near-lethal doses permethrin. If hypothesis is correct, then blood play an important "buffering" role protecting against population at large. It also suggests individuals low esterase activity predisposed neurologic deficits certain chemical mixtures.