Pretreatment of rats with an organophosphorus insecticide, chlorfenvinphos, protects against subsequent challenge with the same compound.
A single oral pretreatment of rats with chlorfenvinphos (CVP) reduced toxicity of the same compound subsequently administered. This protection occurred 8 hr and became maximal 24 hr after the oral pretreatment at a dose of 15 mg/kg (about half of its LD50). The 24-hr pretreatment with CVP increased the LD50 of CVP threefold, but did not change the type of toxic signs and time to death caused by CVP. The CVP pretreatment did not appreciably change the toxicities of the cholinergic agonists, carbachol and oxotremorine, but significantly increased the toxicity of another organophosphate, dichlorvos. Oral treatment of rats with CVP (15 mg/kg) inhibited brain acetylcholinesterase (AChE) activity. This inhibition became maximal at 4 hr (about 20% of control) and lasted more than 24 hr after the administration. Twenty-four hours after oral administration of CVP (15 mg/kg), the second dose (CVP 30 mg/kg, po) was less effective in inhibiting cholinesterase activities of the brain, erythrocyte, and plasma compared with naive rats treated with the same dose. The difference in brain AChE activity between control and CVP pretreatment groups was greater in magnitude than that measured in erythrocytes. CVP concentration in plasma after the oral administration of CVP (30 mg/kg) was decreased by the CVP pretreatment. Area under the concentration vs time curve (AUC) in the CVP-pretreated group was about one-fourth of AUC in the control group. This decrease in the AUC was comparable to the decrease in the toxicity of CVP. Thus, the protection against subsequent CVP challenge may be due to the reduction in the inhibition of brain AChE activity caused by the decrease in plasma CVP concentration.
Ikeda
T
T
Mitsukaido Laboratories, Institute of Environmental Toxicology, Ibaraki, Japan.
Kojima
T
T
Yoshida
M
M
Takahashi
H
H
Tsuda
S
S
Shirasu
Y
Y
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002217:Carbachol / Q000494:pharmacology; D002709:Chlorfenvinphos / Q000097:blood / Q000494:pharmacology* / Q000633:toxicity; D002802:Cholinesterases / Q000378:metabolism; D004006:Dichlorvos / Q000633:toxicity; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D007306:Insecticides / Q000494:pharmacology*; D007928:Lethal Dose 50; D008297:Male; D010095:Oxotremorine / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D007306:Insecticides; D010095:Oxotremorine; D004006:Dichlorvos; D002217:Carbachol; D000110:Acetylcholinesterase; D002802:Cholinesterases; D002709:Chlorfenvinphos