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 poten tial 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 ra ts were treated orally with chlorpyrifos during late gestation (Gestational Days 14-18). Following euthanasia the level of chlorpyrifos and its metabo lites, chlorpyrifos-oxon and 3,5,6-trichloro-2-pyridinol (TCP), were measur ed 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 in hibition 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 c holinesterase activity showed the same time of peak effect: 5 h after the l ast dose. The concentration of TCP in the maternal liver was approximately fivefold higher than the TCP concentration in fetal liver, but, paradoxical ly, 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 resul ts suggest that the fetal nervous system may be exposed to a higher concent ration of chlorpyrifos than the maternal nervous system when the dam is ora lly exposed to chlorpyrifos during late gestation.