Comparison of Fetal and Maternal Brain Cholinesterase Activity Following Repeated Versus Single Late Gestational Exposure to Chlorpyrifos

Abstract

Previous studies have shown that the fetal brain cholinesterase (ChE) is often less inhibited than the maternal brain ChE after dosing of a pregnant rat with an anticholinesterase pesticide. One of the generally offered explanations for this apparent “protection” of the fetus is that maternal and placental detoxification of the anticholinesterase shields the fetal brain ChE from inhibition. This present study investigates the dose response profiles of the target enzyme ChE and the detoxification enzyme 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 organo-phosphorus insecticide. Pregnant rats were dosed daily (p. o.) with chlorpyrifos in corn oil (0, 3, 5, 7, or 10 mg/kg) on gestational days (GD) 14–18. An additional set of pregnant rats received a single dose of 10 mg/kg chlorpyrifos on GD18. Animals were sacrificed 5 hours (time of maximum inhibition) after the last chlorpyrifos dose and maternal blood, liver, brain, placenta, and fetal liver and brain were collected for ChE and CaE activity analysis. Using these dosing regimens, we found that (1) inhibition of fetal and maternal brain ChE was dose dependent, (2) after repeated dosing there was nearly 5 fold less inhibition of fetal brain ChE than maternal brain ChE, (3) after a single dose there was comparable inhibition of fetal and maternal brain ChE. Furthermore, in control animals the activity of the detoxification enzyme CaE in the fetal tissues was very low compared to the maternal tissues. Using inhibition of CaE as an “index” of protective value, the fetal liver CaE was the only fetal tissue demonstrating protection. Fetal liver activity was 50% of control activity irrespective of dose.