PMID- 9772200 OWN - NLM STAT- MEDLINE DCOM- 19981120 LR - 20141120 IS - 0041-008X (Print) IS - 0041-008X (Linking) VI - 152 IP - 1 DP - 1998 Sep TI - Gestational exposure to chlorpyrifos: apparent protection of the fetus? PG - 56-65 AB - Previous studies have shown that, in general, young, postnatal animals are more sensitive than adults to the toxic effects of anticholinesterase (antiChE) pesticides. Paradoxically, often fetal brain cholinesterase (ChE) is less inhibited than maternal brain after gestational exposure to an antiChE, presumably due to placental and fetal detoxification of the antiChE. The present investigation was designed to study selected toxicokinetic and toxicodynamic factors surrounding the toxicity of chlorpyrifos (CPF; [O,O'-diethyl O-3,5,6-trichloro-2-pyridyl] phosphorothionate) in pregnant rats dosed repeatedly or singly during late gestation. Dams were dosed daily (po) with CPF in corn oil (0 or 7 mg/kg) on gestational days (GD) 14 to 18. Animals were euthanized at 2 to 120 h after the last dose and tissues were collected for enzyme analysis. Using this dosing regimen, we found that (1) the time of maximal ChE inhibition was the same (i.e., 5-10 h after dosing) for both maternal and fetal brain, (2) the degree of fetal brain ChE inhibition was 4.7 times less than maternal brain inhibition, and (3) the detoxification potential (i.e., carboxylesterase and chlorpyrifos-oxonase) of the fetal tissues was very low compared to the maternal tissues. A separate group of experiments showed that if pregnant dams received only one oral dose of 7 or 10 mg/kg CPF on GD18, the degree of ChE inhibition in the fetal brain was comparable to the maternal brain ChE inhibition. Taking into consideration the net increase (more than fourfold) in fetal brain ChE activity from GD14 to 18 in control animals, and the fact that maternal brain ChE was inhibited more than fetal brain ChE only in a repeated-dosing regimen, we conclude that the fetus is not genuinely protected from the toxic effects of a given dose of CPF. We propose that fetal brain ChE is simply able to recover more fully between each dose as compared to maternal brain ChE, giving the illusion that the fetal compartment is less affected than the maternal compartment. FAU - Lassiter, T L AU - Lassiter TL AD - Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina, USA. FAU - Padilla, S AU - Padilla S FAU - Mortensen, S R AU - Mortensen SR FAU - Chanda, S M AU - Chanda SM FAU - Moser, V C AU - Moser VC FAU - Barone, S Jr AU - Barone S Jr LA - eng GR - T32 ES07126/ES/NIEHS NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Toxicol Appl Pharmacol JT - Toxicology and applied pharmacology JID - 0416575 RN - 0 (Cholinesterase Inhibitors) RN - EC 3.1.- (Esterases) RN - EC 3.1.1.- (Carboxylic Ester Hydrolases) RN - EC 3.1.1.1 (Carboxylesterase) RN - EC 3.1.1.8 (Cholinesterases) RN - EC 3.1.8.- (chlorpyrifos-oxonase) RN - JCS58I644W (Chlorpyrifos) SB - IM MH - Animals MH - Brain/*drug effects/enzymology MH - Brain Diseases/chemically induced/enzymology/*prevention & control MH - Carboxylesterase MH - Carboxylic Ester Hydrolases/metabolism MH - Chlorpyrifos/administration & dosage/*toxicity MH - Cholinesterase Inhibitors/administration & dosage/*toxicity MH - Cholinesterases/metabolism MH - Embryonic and Fetal Development/*drug effects MH - Esterases/metabolism MH - Female MH - Fetus/enzymology MH - Gestational Age MH - Inactivation, Metabolic MH - Liver/drug effects/embryology/enzymology MH - Pregnancy MH - *Prenatal Exposure Delayed Effects MH - Rats MH - Rats, Long-Evans EDAT- 1998/10/17 02:11 MHDA- 2001/03/28 10:01 CRDT- 1998/10/17 02:11 PHST- 1998/10/17 02:11 [pubmed] PHST- 2001/03/28 10:01 [medline] PHST- 1998/10/17 02:11 [entrez] AID - S0041-008X(98)98514-3 [pii] AID - 10.1006/taap.1998.8514 [doi] PST - ppublish SO - Toxicol Appl Pharmacol. 1998 Sep;152(1):56-65. doi: 10.1006/taap.1998.8514.