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

Abstract

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.

Key Words::

• Toxicology
• pharmacokinetics
• fenitrothion
• neurotoxicity
• esterases
• rodent

Acknowledgements

The authors would like to thank Dr Mel Andersen and Dr Teresa Leavens for their review of this manuscript. They would also like to thank the CIIT animal care staff for their assistance with the project. This project was funded through the American Chemistry Council's support of the Center for Developmental Dosimetry at CIIT.