Inhibition and recovery of maternal and foetal cholinesterase enzymes following fenitrothion administration in CD rats

• Published in: Xenobiotica 2007-01, Vol.37 (1), p.19-29
• Main Authors: Sochaski, M. A., McManus, B. M., Struve, M. F., Wallace, D. G., Dorman, D. C.
• Format: Article
• Language: English
• Subjects: Animals; Brain - drug effects; Brain - enzymology; Cholinesterase Inhibitors - administration & dosage; Cholinesterase Inhibitors - blood; Cholinesterase Inhibitors - pharmacokinetics; Cholinesterase Inhibitors - pharmacology; Cholinesterases - metabolism; esterases; Female; fenitrothion; Fenitrothion - administration & dosage; Fenitrothion - blood; Fenitrothion - pharmacokinetics; Fenitrothion - pharmacology; Fetus - drug effects; Fetus - enzymology; Liver - drug effects; Liver - enzymology; neurotoxicity; pharmacokinetics; Pregnancy; Rats; rodent; Toxicology
• ISSN: 0049-8254; 1366-5928
• DOI: 10.1080/00498250600966360

The purpose of this study was to characterize tissue esterase activity and blood fenitrothion concentrations in the rat dam and foetus following in-utero exposure to the organophosphate insecticide fenitrothion. Time-mated, 8-week-old rats were gavaged on gestation day 19 with 0, 5, or 25 mg fenitrothion kg−1. Fenitrothion was absorbed rapidly from the gastrointestinal tract, with peak maternal and foetal blood levels observed 0.5-1.0 h after dosing. Fenitrothion concentrations in maternal and foetal blood were virtually identical and demonstrated a non-linear dose-response relationship. Acetylcholinesterase and carboxylesterase activities in maternal liver and blood and in foetal liver and brain decreased within 30-60 min of fenitrothion exposure. Esterase inhibition occurred at a fenitrothion dose (5 mg kg−1) that has not been previously associated with reproductive toxicity, suggesting that esterase inhibition should be considered as the critical effect in risk assessments for this pesticide.