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Prenatal exposure to organophosphates, paraoxonase 1, and cognitive development in childhood.

Authors
Engel-SM; Wetmur-J; Chen-J; Zhu-C; Barr-DB; Canfield-RL; Wolff-MS
Source
Environ Health Perspect 2011 Aug; 119(8):1182-1188
NIOSHTIC No.
20040113
Abstract
BACKGROUND: Prenatal exposure to organophosphate pesticides has been shown to negatively affect child neurobehavioral development. Paraoxonase 1 (PON1) is a key enzyme in the metabolism of organophosphates. OBJECTIVE: We examined the relationship between biomarkers of organophosphate exposure, PON1, and cognitive development at ages 12 and 24 months and 6-9 years. METHODS: The Mount Sinai Children's Environmental Health Study enrolled a multiethnic prenatal population in New York City between 1998 and 2002 (n = 404). Third-trimester maternal urine samples were collected and analyzed for organophosphate metabolites (n = 360). Prenatal maternal blood was analyzed for PON1 activity and genotype. Children returned for neurodevelopment assessments ages 12 months (n = 200), 24 months (n = 276), and 6-9 (n = 169) years of age. RESULTS: Prenatal total dialkylphosphate metabolite level was associated with a decrement in mental development at 12 months among blacks and Hispanics. These associations appeared to be enhanced among children of mothers who carried the PON1 Q192R QR/RR genotype. In later childhood, increasing prenatal total dialkyl- and dimethylphosphate metabolites were associated with decrements in perceptual reasoning in the maternal PON1 Q192R QQ genotype, which imparts slow catalytic activity for chlorpyrifos oxon, with a monotonic trend consistent with greater decrements with increasing prenatal exposure. CONCLUSION: Our findings suggest that prenatal exposure to organophosphates is negatively associated with cognitive development, particularly perceptual reasoning, with evidence of effects beginning at 12 months and continuing through early childhood. PON1 may be an important susceptibility factor for these deleterious effects.
Keywords
Humans; Children; Drugs; Pesticides; Pesticides-and-agricultural-chemicals; Nervous-system-disorders; Nervous-system; Neurological-system; Neuromuscular-function; Neuromuscular-system-disorders; Biomarkers; Genotoxic-effects; Genotoxicity; Exposure-levels; Exposure-limits; Pregnancy; Prenatal-exposure; Author Keywords: environmental exposures; IQ; mental development; organophosphates; pesticides
Contact
Stephanie M. Engel, Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina-Chapel Hill, 2104C McGavran-Greenberg, Box 7435, Chapel Hill, NC 27599-7435
CODEN
EVHPAZ
Publication Date
20110801
Document Type
Journal Article
Email Address
Stephanie.Engel@unc.edu
Funding Type
Grant
Fiscal Year
2011
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-007400; B01182012
Issue of Publication
8
ISSN
0091-6765
Source Name
Environmental Health Perspectives
State
GA; NY; NC
Performing Organization
University of California, Berkeley
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