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THE ANTICHOLINESTERASE INSECTICIDE, DIAZINON, MAY POTENTIATE THE TOXICITY OF THE PYRETHROID INSECTICIDE DELTAMETHRIN AT LOW DOSAGES.
Citation:
Haines, W. T., M. M. Taylor, K M. Crofton, R S. Marshall, AND S J. Padilla. THE ANTICHOLINESTERASE INSECTICIDE, DIAZINON, MAY POTENTIATE THE TOXICITY OF THE PYRETHROID INSECTICIDE DELTAMETHRIN AT LOW DOSAGES. Presented at Society of Toxicology, San Francisco, CA, 3/24/01-3/29/01.
Description:
This present study explores the interaction of the toxicity induced by an organophosphorus insecticide, diazinon (diethyl 2-isopropyl-6methyl-4-pyrimidal phosphorothionate), with a pyrethroid insecticide, deltamethrin ((S)-a-cyano-3-phenoxybenzyl (1R,3R)-3-(2,2-dibromovinyl)-2,2-di-methylcyclopropanecarboxylate). Even though these two compounds have different mechanisms of toxicity (i.e., diazinon is a cholinesterase inhibitor, while deltamethrin causes prolonged Na+ channel depolarization), both insecticides are detoxified via carboxylesterases. The objective of the study was to determine if prior administration of diazinon (DIA) would accentuate the subsequent effects of deltamethrin (DLT). Adult, Long-Evans, male rats (n = 8/group) were orally dosed with 20 mg/kg DIA (LD50>1200 mg/kg) or the corn oil vehicle, and 24 hours later orally dosed with 0 or 1 mg/kg DLT (LD50>128 mg/kg). Two hours after DLT (at the time of peak effect for DLT), acute toxicity was assessed by measuring motor activity in a figure-8 maze. DLT or DIA alone at any dosage did not decrease motor activity. When combined, those animals pretreated with 20 mg/kg DIA and then treated with 1 mg/kg DLT animals showed approximately a 25% decrease in motor activity. This dose of DIA did not inhibit brain cholinesterase activity, either with or without DLT; however, 20 mg/kg DIA inhibited liver carboxylesterase activity by about 60%. These results suggest low dosages of DIA potentiate the neurotoxic effects of DLT by inhibiting the detoxification of DLT by carboxylesterase. (This is an abstract of a proposed presentation and does not necessarily reflect EPA policy).