Metal Mixtures and Children’s Neurodevelopment

EPA Grant Number: FP916900
Title: Metal Mixtures and Children’s Neurodevelopment
Investigators: Henn, Birgit Claus
Institution: Harvard T.H. Chan School of Public Health
EPA Project Officer: Hahn, Intaek
Project Period: October 1, 2007 through October 1, 2010
RFA: STAR Graduate Fellowships (2007) RFA Text |  Recipients Lists
Research Category: Fellowship - Environmental Epidemiology , Health Effects , Academic Fellowships


Among children, neurodevelopmental toxicity is a primary adverse health effect due to exposure to toxic metals. While the effects of certain metals, such as lead, have been extensively described, the neurodevelopmental effects of other metals, including manganese and arsenic, remain to be fully characterized. Exposure to combinations of metals, which represents a more realistic exposure scenario, may result in greater adverse effects than from exposure to each metal alone. This project will examine the association of prenatal and early childhood exposure to manganese with neurodevelopment, utilizing two unique populations: 1) a rural cohort of children living near a hazardous waste site (Tar Creek, OK) and 2) an urban cohort of children residing in Mexico City. This study will be among the first to explore interactions between exposure to metals in children (i.e., metal mixtures), as well as interactions between exposure to metals and genetic polymorphisms (i.e., gene-environment interactions).


A prospective observational study will be conducted in children up to 3 years of age to (1) evaluate the association between childhood exposure to manganese, measured in hair and blood biomarkers, and neurodevelopmental scores, (2) examine whether exposure to mixtures of manganese, arsenic, and lead cause neurodevelopmental deficiencies that are more severe than from exposure to each metal alone, and (3) explore whether polymorphisms in the hemochromatosis (HFE) gene modify the neurological effects of lead, manganese, and arsenic. Two cohorts of children will be examined: one living near the Tar Creek Superfund Site in Oklahoma, and one residing in Mexico City.

Expected Results:

Since manganese is an essential nutrient, it is expected that children who were exposed to the highest and lowest levels of manganese will have lower neurodevelopmental scores than children who were exposed to moderate levels of manganese. Neurodevelopmental scores are also expected to be lower in children exposed to high levels of more than one metal compared to children exposed to just one metal alone. Since genetic polymorphisms such as variants in the HFE gene may affect the activity of transport proteins for metals, these polymorphisms may alter the neurotoxic effects of metals, thus changing host susceptibility.

Supplemental Keywords:

children’s health, neurodevelopment, metal mixtures, manganese, lead, arsenic, biomarkers, health effects, genetic susceptibility, hemochromatosis gene, polymorphisms,

Progress and Final Reports:

  • 2008
  • 2009
  • Final