Gestational exposure to chlorpyrifos: dose response profiles for cholinesterase and carboxylesterase activity

This study investigates the in vivo dose response profiles of the targetenzyme cholinesterase (ChE) and the detoxifying enzymes carboxylesterase(CaE) in the fetal and maternal compartments of pregnant rats dosed withchlorpyrifos [(O,O'-diethyl O-3,5,6-trichloro- 2-pyridyl)phosphorothionate], a commonly used organophosphorus insecticide. Pregnantrats were dosed daily (po) with chlorpyrifos in corn oil (0, 3, 5, 7, or 10mg/kg) on gestational days (GD) 14-18. Animals were sacrificed 5 h afterthe last chlorpyrifos dose (time of maximum brain cholinesteraseinhibition) for analysis of ChE and CaE activity in maternal blood, liver,brain, placenta, and fetal liver and brain. The in vitro sensitivity (i.e.,IC50, 30 min, 26 degrees C) of CaE also was determined by assaying theactivity remaining after incubation with a range of chlorpyrifos-oxonconcentrations. In vivo exposure to 10 mg/kg chlorpyrifos from GD14-18caused overt maternal toxicity, with dose-related decreases in ChE activitymore notable in maternal brain than fetal brain. Dose-related effects werealso seen with chlorpyrifos-induced inhibition of fetal liver ChE andmaternal brain CaE activities. Gestational exposure caused no inhibition ofplacental ChE or CaE, fetal brain CaE, or maternal blood CaE. ChEactivities in the maternal blood and liver, as well as fetal and maternalliver CaE, however, were maximally inhibited by even the lowest dosage ofchlorpyrifos. The in vitro sensitivity profiles of CaE to chlorpyrifos-oxoninhibition were valuable in predicting and verifying the in vivo CaEresponse profiles. Both the in vivo and in vitro findings indicated thatfetal liver CaE inhibition was an extremely sensitive indicator of fetalchlorpyrifos exposure.