Chlorpyrifos, an insecticide implicated as a developmental neurotoxicant in animals, is utilized routinely in the homes of inner city residents. As part of an effort to measure the associated neurodevelopmental risks to specific individuals in this population, the paraoxonase and butyryl- cholinesterase enzyme kinetics and acetylcholinesterase activities will be determined in maternal and cord blood of greater than or equal to 150 African-American and greater than or equal to 150 Hispanic mother-infant pairs who are part of the prospective epidemiological study cohort from Project 2, as well as greater than or equal to 100 Caucasian mother- infant pairs. One of the substrates for determining the enzyme kinetics will be chlorpyrifos oxon. The substrates for paraoxonase and arylesterase activities of paraoxonase will be selected to distinguish these activities. Butyrylcholinesterase also will be assayed with multiple substrates and inhibitors. The frequency of polymorphisms (or mutations) in the paraoxonase and butyryl-cholinesterase genes will be determined in the same three population groups. For both enzymes, the well established polymorphisms or mutations will be determined. Where the chlorpyrifos oxon and other substrate specificities do not agree with expectation for the known polymorphisms or mutations, the exon sequences and splice junctions will be determined. In samples with a very low enzymatic activity, the promoters will be investigated to relate phenotype to genotype. In samples with a very low enzymatic activity, the promoters will be investigated to related phenotype to genotype. An in vitro model will be established to determine the relative contributions of paraoxonase and butyrylcholinesterase to detoxification of low concentrations of chlorpyrifos and related compounds. This phenotypic model will permit conversion of measurements of total exposure to chlorpyrifos to specific exposures to the oxon. The conversion factors for a genotypic model also will be determined. Finally, effects of specific exposure to chlorpyrifos oxon the neurodevelopment of exposed neonates in minority populations in East Harlem will be determined using both phenotypic and genotypic data.
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