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

This study investigates the in vivo dose response profiles of the target en zyme cholinesterase (ChE) and the detoxifying enzymes carboxylesterase (CaE ) in the fetal and maternal compartments of pregnant rats dosed with chlorp yrifos [(O,O'-diethyl O-3,5,6-trichloro-2-pyridyl) phosphorothionate], a co mmonly used organophosphorus insecticide. Pregnant. rats were dosed daily ( po) with chlorpyrifos in corn oh (0, 3, 5, 7, or 10 mg/kg) on gestational d ays (GD) 14-18, Animals were sacrificed 5 h after the last chlorpyrifos dos e (time of maximum brain cholinesterase inhibition) for analysis of ChE and CaE activity in maternal blood, liver, brain, placenta, and fetal liver an d brain. The in vitro sensitivity (i.e., IC50, 30 min, 26 degrees C) of CaE also was determined by assaying the activity remaining after incubation wi th a range of chlorpyrifosxon concentrations, In vivo exposure to 10 mg/kg chlorpyrifos from GD14-18 caused overt maternal toxicity, with dose-related decreases in ChE activity more notable in maternal brain than fetal brain. Dose-related effects were also seen with chlorpyrifos-induced inhibition o f fetal liver ChE and maternal brain CaE activities. Gestational exposure c aused no inhibition of placental ChE or CaE, fetal brain CaE, or maternal b lood CaE, ChE activities in the maternal blood and liver,as well as fetal a nd maternal liver CaE, however, were maximally inhibited by even the lowest dosage of chlorpyrifos. The in vitro sensitivity profiles of CaE to chlorp yrifos-oxon inhibition were valuable in predicting and verifying the in viv o CaE response profiles. Both the in vivo and in vitro findings indicated t hat fetal liver CaE inhibition was an extremely sensitive indicator of feta l chlorpyrifos exposure. brain; dose response; butyrylcholinesterase; acety lcholinesterase.