Toxicological Sciences, Vol 52, 92-100, Copyright © 1999 by Society of Toxicology
TL Lassiter, S Barone Jr, VC Moser and S Padilla
This study investigates the in vivo dose response profiles of the target
enzyme cholinesterase (ChE) and the detoxifying enzymes carboxylesterase
(CaE) in the fetal and maternal compartments of pregnant rats dosed with
chlorpyrifos [(O,O'-diethyl O-3,5,6-trichloro- 2-pyridyl)
phosphorothionate], a commonly used organophosphorus insecticide. Pregnant
rats were dosed daily (po) with chlorpyrifos in corn oil (0, 3, 5, 7, or 10
mg/kg) on gestational days (GD) 14-18. Animals were sacrificed 5 h after
the last chlorpyrifos dose (time of maximum brain cholinesterase
inhibition) 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 the
activity remaining after incubation with a range of chlorpyrifos-oxon
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 of fetal liver ChE and
maternal brain CaE activities. Gestational exposure caused no inhibition of
placental ChE or CaE, fetal brain CaE, or maternal blood CaE. ChE
activities in the maternal blood and liver, as well as fetal and maternal
liver CaE, however, were maximally inhibited by even the lowest dosage of
chlorpyrifos. The in vitro sensitivity profiles of CaE to chlorpyrifos-oxon
inhibition were valuable in predicting and verifying the in vivo CaE
response profiles. Both the in vivo and in vitro findings indicated that
fetal liver CaE inhibition was an extremely sensitive indicator of fetal
chlorpyrifos exposure.
ARTICLES
Gestational exposure to chlorpyrifos: dose response profiles for cholinesterase and carboxylesterase activity
Curriculum in Toxicology, University of North Carolina, Chapel Hill, USA. lassiter.leon@epamail.epa.gov
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