Exposure to metal mixtures in multiple critical periods of development and adolescent neuromotor function

项目总结/文摘

Project Summary/Abstract Evidence for neurodevelopmental toxicity from exposure to environmental metals is mounting. Recent studies have found that neurotoxicity may depend on when during development the metal exposure occurs (e.g., in utero versus childhood) and that metals have synergistic adverse effects on children's neurodevelopment. Our study aims to elucidate the role of childhood environmental metal exposure on neuromotor function, a largely understudied neurodevelopmental outcome, by examining cumulative and interactive associations with a common industrial metal mixture. The proposed research in this F31 will use previously collected data from the Public Health Impact of Mixed Element exposure (PHIME) study, comprised of 720 children (ages 10-14 years) with varied airborne exposure to ferroalloy industry pollutants in Italy. Under the mentorship of a multidisciplinary team of experts in environmental epidemiology, neurobehavioral toxicology, exposure biology, statistical methods and chemical mixtures, Alexa Friedman (PI) proposes to estimate the associations of an industrially relevant metal mixture of manganese, copper, chromium and lead with neuromotor function in multiple critical periods of development. We will evaluate the relationship between metals, measured in multiple biomarkers (teeth, hair, nails, blood, saliva, urine) that represent exposure from the prenatal period through adolescence, and a battery of neuropsychological tests that evaluate motor function. We will use state- of-the-art statistical approaches, including Bayesian Kernel Machine Regression and quantile-based g- computation for metal mixtures, and hierarchical variable selection to examine biomarker selection. This research will inform our current understanding of metal associations with children's neuromotor function and provide insights for targeted interventions to reduce metals exposure. It also targets several NIEHS strategic goals including the study of co-exposures in communities living near environmental hazards and the innovative use of exposure data across critical developmental windows.