Acute toxicity of two pyrethroids, permethrin, and cypermethrin in neonatal and adult rats.
The present study aims specifically at obtaining a comparison of the acute toxicity of cypermethrin (CY), a type I pyrethroid, and permethrin (PERM), a type II pyrethroid, administered orally as a single dose to neonatal and adult rats, and at assessing the importance of pyrethroid biotransformation in CY and PERM toxicity through use of drug metabolism inhibitors. Our experiments show that CY is more toxic than PERM to adult and neonatal rats. The sensitivity of neonatal rats both to CY and to PERM toxicity is higher, the younger the animals. CY is much more toxic than PERM in the neonatal rat, compared with the adult. In rats aged 8, 16, and 21 days, pretreatment with piperonyl butoxide (PB), a monooxygenase inhibitor, or with tri-o-tolyl phosphate (TOTP), an esterase inhibitor, does not produce significant variations in the lethal effects of CY and PERM. Instead, in the adult rats, a significant increase in CY (chi 2 = 5.97; p < 0.05) and PERM (chi 2 = 4.37; p < 0.05) mortality occurred in rats pretreated with esterase inhibitors, whereas no increase in CY and PERM toxicity was found in adult animals pretreated with monooxygenase inhibitor. It was concluded that the higher level of sensitivity of the neonate rat to pyrethroid toxicity is probably due to incomplete development of the enzymes which catalyze the metabolism of pyrethroids in the liver of young animals. It is suggested that ester hydrolysis is an important pyrethroids detoxification reaction in the adult rat.
Cantalamessa
F
F
Institute of Pharmacology, University of Camerino, Italy.
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001711:Biotransformation; D004950:Esterases / Q000037:antagonists & inhibitors; D005260:Female; D007306:Insecticides / Q000493:pharmacokinetics / Q000633:toxicity*; D007928:Lethal Dose 50; D008297:Male; D026023:Permethrin; D010882:Piperonyl Butoxide / Q000494:pharmacology; D011722:Pyrethrins / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D014317:Tritolyl Phosphates / Q000494:pharmacology
D007306:Insecticides; D011722:Pyrethrins; D014317:Tritolyl Phosphates; C017160:cypermethrin; D026023:Permethrin; D004950:Esterases; D010882:Piperonyl Butoxide; C025541:tri-o-cresyl phosphate