The research in this revised proposal will be performed primarily in India as an extension of NIH grant #R01 ES07821. Lead exposure poses a major environmental health problem in India. No direct studies have yet been performed in India to investigate the impact of lead exposure on outcomes such as neurobehavioral development. We propose to build upon a collaborative effort initiated during the proposed PI's work as a Senior Fulbright Scholar and work with colleagues at the Sri Ramachandra Medical College and Research Institute of Chennai (formerly known as Madras), Tamil Nadu, India, to study 750 children aged 4-6 attending specific public schools in the area of Chennai. These schools will be chose to represent areas of the city that are high-high, high-low, low-high, and low-low with respect to traffic and industry. For each child we will measure levels of lead in blood and shed primary teeth; assess visuospatial function (using Raven's Progressive Matrices), visuomotor function (using the Wide Range Assessment of Visual Motor Abilities), behavior (using Conners' Rating Scale-Revised), and IQ (using the Binet-Kamath test); collect blood for the extraction of DNA and genotyping for polymorphisms of the aminolevulinic acid dehydratase (ALAD), apoliproprotein E, and transferrin genes; and collect data on covariates. With this information we will describe lead exposure and exposure-dose relationships and test specific hypotheses on the relationship of lead dose to neurobehavioral outcomes and the modifying effect of genetic polymorphisms on these same relationships. This research promises to provide novel scientific information on lead toxicity as well as important information on the impact of lead exposure on pediatric neurobehavioral development in urban India. It will also serve as a nidus for building collaborative environmental health research between the U.S. and India.
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