Differences in the mode of lethality produced through intravenous and oral administration of organophosphorus insecticides in rats.
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 P = O type insecticide (direct ChE inhibitors: chlorfenvinphos and dichlorvos) and the P = S type insecticide (indirect ChE inhibitors: diazinon and fenthion) were employed. Rats treated with lethal doses of intravenous and oral P = O type insecticides and oral P = S 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 P = S type insecticides exhibited tonic convulsions and opisthotonos, with only slight inhibition of ChE activities. When P = O 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 P = O type insecticides, breathing disappeared before the cessation of heart beats. Rats receiving lethal doses of intravenous P = S 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 P = S type insecticides may be independent of ChE inhibition.
Takahashi
H
H
Mitsukaido Laboratories, Institute of Environmental Toxicology, Ibaraki, Japan.
Kojima
T
T
Ikeda
T
T
Tsuda
S
S
Shirasu
Y
Y
D000284:Administration, Oral; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002802:Cholinesterases / Q000378:metabolism; D004569:Electroencephalography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D009943:Organophosphorus Compounds; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects
D007306:Insecticides; D009943:Organophosphorus Compounds; D002802:Cholinesterases