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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Program Projects (P01)
Project #
5P01ES009584-04
Application #
6564421
Study Section
Project Start
2001-11-01
Project End
2002-10-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
4
Fiscal Year
2002
Total Cost
$230,840
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10029
Dobraca, Dina; Lum, Raymond; Sjödin, Andreas et al. (2018) Urinary biomarkers of polycyclic aromatic hydrocarbons in pre- and peri-pubertal girls in Northern California: Predictors of exposure and temporal variability. Environ Res 165:46-54
Buckley, Jessie P; Quirós-Alcalá, Lesliam; Teitelbaum, Susan L et al. (2018) Associations of prenatal environmental phenol and phthalate biomarkers with respiratory and allergic diseases among children aged 6 and 7?years. Environ Int 115:79-88
Furlong, Melissa; Herring, Amy H; Goldman, Barbara D et al. (2018) Early Life Characteristics and Neurodevelopmental Phenotypes in the Mount Sinai Children's Environmental Health Center. Child Psychiatry Hum Dev 49:534-550
Keil, Alexander P; Daza, Eric J; Engel, Stephanie M et al. (2018) A Bayesian approach to the g-formula. Stat Methods Med Res 27:3183-3204
Furlong, Melissa A; Barr, Dana Boyd; Wolff, Mary S et al. (2017) Prenatal exposure to pyrethroid pesticides and childhood behavior and executive functioning. Neurotoxicology 62:231-238
Singer, Alison B; Wolff, Mary S; Silva, Manori J et al. (2017) Prenatal phthalate exposures and child temperament at 12 and 24 months. Neurotoxicology 62:248-257
Wolff, Mary S; Pajak, Ashley; Pinney, Susan M et al. (2017) Associations of urinary phthalate and phenol biomarkers with menarche in a multiethnic cohort of young girls. Reprod Toxicol 67:56-64
Hiatt, Robert A; Stewart, Susan L; Hoeft, Kristin S et al. (2017) Childhood Socioeconomic Position and Pubertal Onset in a Cohort of Multiethnic Girls: Implications for Breast Cancer. Cancer Epidemiol Biomarkers Prev 26:1714-1721
Windham, Gayle C; Lum, Raymond; Voss, Robert et al. (2017) Age at Pubertal Onset in Girls and Tobacco Smoke Exposure During Pre- and Postnatal Susceptibility Windows. Epidemiology 28:719-727
Buckley, Jessie P; Doherty, Brett T; Keil, Alexander P et al. (2017) Statistical Approaches for Estimating Sex-Specific Effects in Endocrine Disruptors Research. Environ Health Perspect 125:067013

Showing the most recent 10 out of 84 publications