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© 1991 Oxford University Press

research-article

Differences in the Mode of Lethality Produced through Intravenous and Oral Administration of Organophosphorus Insecticides in Rats1

HIROAKI TAKAHASHI, TAKESHI KOJIMA, TAKANORI IKEDA, SHUJI TSUDA and YASUHIKO SHIRASU

Mitsukaido Laboratories, Institute of Environmental Toxicology Uchimoriya-cho 4321, Mitsukaido-shi, Ibaraki 303, Japan

Received May 29, 1990; accepted October 29, 1990

Differences in the Mode of Lethality Produced through Intravenous and Oral Administration of Organophosphorus Insecticides in Rats. TAKAHASHI, H., KOJIMA, T., IKEDA, T., TSUDA, S. and SHIRASU, Y. (1991). Fundam. Appl. Toxicol. 16, 459–468. This study was undertaken to investigate the possibility that mechanisms other than cholinesterase (ChE) inhibition account for the acute toxicity of organophosphorus insecticide. Both the PO type insecticide (direct ChE inhibitors: chlorfenvinphos and dichlorvos) and the PS type insecticide (indirect ChE inhibitors: diazinon and fenthion) were employed. Rats treated with lethal doses of intravenous and oral PO type insecticides and oral PS type insecticides exhibited typical signs of anti-ChE poisoning along with marked inhibition of brain and erythrocyte ChE activity. In contrast, rats given lethal doses of intravenous PS type insecticides exhibited tonic convulsions and opisthotonos, with only slight inhibition of ChE activities. When PO type insecticides were intravenously administered to anesthetized and conscious rats, animals exhibited typical anti-ChE poisoning signs in cardiorespiration: hypertension and apnea which were antagonized by atropine. After administration of lethal doses of PO type insecticides, breathing disappeared before the cessation of heart beats. Rats receiving lethal doses of intravenous PS type insecticides did not show hypertension, but exhibited transient cessation of breathing and heart beats. Breathing was observed after the disappearance of heart beats. The electroencephalogram (EEG) was characterized by spike and wave complexes. The EEG and cardiorespiratory changes were not antagonized by atropine. It was concluded that lethality following intravenous PS type insecticides may be independent of ChE inhibition.


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