Gestational exposure to chlorpyrifos: comparative distribution of trichloropyridinol in the fetus and dam.
Chlorpyrifos (O,O'-diethyl O-[3,5,6-trichloro-2-pyridyl] phosphorothionate) is a commonly used anticholinesterase insecticide, and therefore the potential for human exposure is high. The present time course and dose response studies were conducted to delineate the toxicokinetics of chlorpyrifos and its metabolites in the pregnant rat and fetus. Time-pregnant, Long-Evans rats were treated orally with chlorpyrifos during late gestation (Gestational Days 14-18). Following euthanasia the level of chlorpyrifos and its metabolites, chlorpyrifos-oxon and 3,5,6-trichloro-2-pyridinol (TCP), were measured in both fetal and maternal brain and liver (limits of quantitation: 59.2, 28.8, and 14.0 ng/g tissue, respectively). In addition, cholinesterase inhibition was also measured in the same tissues for comparison. TCP was the only component detected. The highest level of TCP and the lowest level of cholinesterase activity showed the same time of peak effect: 5 h after the last dose. The concentration of TCP in the maternal liver was approximately fivefold higher than the TCP concentration in fetal liver, but, paradoxically, the concentration of TCP in the fetal brain was two- to fourfold higher than the TCP concentration in the maternal brain. The half-life of the TCP was identical in all tissues examined (12-15 h). These toxicokinetic results suggest that the fetal nervous system may be exposed to a higher concentration of chlorpyrifos than the maternal nervous system when the dam is orally exposed to chlorpyrifos during late gestation.
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Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. hunter.deborah@epamail.epa.gov
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D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D004390:Chlorpyrifos / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics* / Q000633:toxicity; D002802:Cholinesterases / Q000378:metabolism; D002845:Chromatography; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000378:metabolism*; D007306:Insecticides / Q000493:pharmacokinetics* / Q000633:toxicity; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D010298:Parity; D011247:Pregnancy; D011728:Pyridones / Q000032:analysis / Q000493:pharmacokinetics*; D051381:Rats; D020318:Rats, Long-Evans; D013997:Time Factors; D014018:Tissue Distribution
D002800:Cholinesterase Inhibitors; D007306:Insecticides; D011728:Pyridones; C012587:3,5,6-trichloro-2-pyridinol; D002802:Cholinesterases; D004390:Chlorpyrifos