Inner City Toxicants, Child Growth & Development

Mount Sinai School of Medicine  

Inner City Toxicants, Child Growth and Development
Mary Wolff, Ph.D.
mary.wolff@mssm.edu

Project Description

Two classes of industrial chemicals with endocrine-disrupting capability - the phthalates and the alkylphenols - have become widely dispersed in the urban built environment, and significant levels of phthalates are now nearly ubiquitous in the bodies of Americans. Highest exposures occur in children and in minorities. Infants and children appear especially susceptible to disruptors, because of their disproportionately heavy exposures and the vulnerability of their still-forming organs to any disruption of the hormonal signaling that irreversibly shapes early development. Yet little is known, either of children's pathways of exposure, or of the human developmental toxicity of endocrine disruptors (EDs). To address these gaps, the goals of the Mount Sinai Center for Children's Environmental Health and Disease Prevention Research are, 1) to characterize the levels and sources of children's exposures to contemporary-use EDs in the urban built environment; 2) to study relationships between EDs and neurobehavioral development; 3) to study relationships among ED exposures, diet, physical activity, and somatic growth; 4) to characterize previously unexplored enzymatic polymorphisms that may modulate individual susceptibility to EDs; and 5) to develop and deploy culturally appropriate, evidence-based strategies in East Harlem to improve children's diets, increase physical activity, reduce obesity, reduce ED exposures, and promote good health. Project 1, the Community-based Prevention Research Project (CBPR), Growing Up Healthy in East Harlem, is built on a long-standing partnership with the East Harlem community. It examines levels and sources of urban children's exposures to EDs and assesses relationships among ED exposures, diet, physical activity, obesity, and use of personal care products. Project 2, an ongoing prospective epidemiological study, analyzes new and previously banked biological samples to examine associations between pre- and post-natal exposures to EDs and growth and development in a cohort study of urban children. This project also continues to assess the developmental effects in this cohort of early exposures to neurotoxicants-organophosphates, pyrethroids, PCBs, and lead - that have been its focus for the past years. Project 3, a molecular genetic study, assesses gene-environment interactions that may influence individual susceptibility to EDs by identifying and characterizing polymorphisms and variations in expression levels of PON1, lipase, and UGT-glucuronyltransferase enzymes involved in ED metabolism. A new Community Outreach and Translation Core (COTC) uses scientific information from the Center to educate and empower community leaders in East Harlem and to inform policy makers and health professionals regionally and nationally about links between the urban environment and children's health. The Center contains an Exposure Assessment Core that collaborates with the laboratories of the Center for Disease Control and Prevention (CDC) National Center for Environmental Health, a Biostatistics and Data Management Core and an Administration Core.

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Project Highlights

A prospective epidemiological study documented that babies exposed in utero to higher levels of organophosphate insecticides are smaller at birth. Notably, decrements in birth weight and birth length were magnified by low maternal expression levels of the pesticide-metabolizing enzyme paraoxonase (PON1). Smaller head circumference is strongly related to PON1 level, and for one pesticide metabolite, an exposure effect was seen only with low-activity PON1. These findings represent newly discovered gene-environment interactions. In this same cohort, Center investigators found that in utero exposures to organophosphates and DDE were associated with measures of neurodevelopmental delay up to age 7 in children. PON1 levels appears to modulate these effects.

To investigate individual susceptibility to pesticides, Center investigators examined linkages of 5 PON SNPs, including PON2. By joining this genetic information with data on PON 1 activity level in maternal prenatal blood and cord blood, Center investigators were able to demonstrate the greater susceptibility of newborns. Their PON1 activity was 1/3rd – 1/5th lower than their mothers’ levels. PON1 levels and infant-maternal proportions also differed by race/ethnicity. For example, Caucasian infants with the CC promoter polymorphism in one SNP had >200% greater PON 1 activity than those with the alternate genotype (vs TT). A grant from NIEHS on Haplotyping for Environmental Genomics was awarded to further develop this technology.

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