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Complex Chemical Mixtures and Heavy Metals
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Much of the research in the field of toxicology and most environmental regulation is concerned with exposure to a single chemical at a time, partly because of the high degree of complexity involved in estimating the dose and health effects from mixtures of chemicals. However, scientists are now beginning to develop the tools necessary to understand the health implications of exposure to chemical mixtures and the Children’s Centers research program is leading the way with some of those projects.
The Center for Children’s Environmental Health and Disease Prevention Research
at the Harvard School of Public Health is specifically investigating the effects
of chemical mixtures on human health and aims to develop interventions to prevent
those effects. The Center is addressing the concerns of a community living
in the Tar
Creek Superfund site in northeastern Oklahoma
, which is highly contaminated
with mixtures of metals in mining waste, including lead, cadmium, iron
and manganese. The
overall goal is to take a highly innovative approach to addressing a "real
world" problem: the potential of the mixtures of metals present in "chat" (mining
waste) to interact with each other in terms of exposure, absorption, dose, and
adverse effects on the development of children.
(courtesy of Vaughn B. Wascovich)
The Center is pursuing four integrated research projects, two of which involve community-based field research with partners at the Tar Creek site, which is part of the Tri-State Mining District that includes areas of Kansas and Missouri and was once one of the world’s largest lead and zinc mining areas. The Tar Creek Superfund site is now one of the largest Superfund sites in the United States covering an area of approximately 50 square miles.
In addition to surface water contamination, there is a significant solid waste problem in the form of mine tailings, or mining waste, known as “chat” piles, which contain high concentrations of heavy metals and vary in size and shape with some as high as 200 feet. The site is estimated to contain about 75 million tons of chat, with many of the piles located near residences in the towns of Picher and Cardin. Some of the chat is sold as a construction product and used for road gravel.
- Exposure to iron oxide has been demonstrated to cause a reduction in transport of manganese and iron in rats, and results suggest that the potential toxicity of these metals can be modified by the level of iron present (Brain et al. 2006).
- Tests in a group of children ages 11-13, from the Tar Creek area have shown that their general intelligence scores, particularly verbal IQ scores, were lower as the levels of manganese (Mn) and arsenic (As) in their bodies increased. Scores on tests of memory for stories and a word list. Were also inversely related to the level of Mn and As. In some cases, a significant Mn-by-As interaction was found (Wright et al. 2006).
Harvard Children’s Environmental Health Center
The objectives of this research project are to: (1) devise a community-based participatory epidemiologic study that examines biological markers of fetal and early childhood exposure to metals (lead, manganese, cadmium, and iron), their impact on measures of mental development, and their response to a quasi-experimental randomized trial of nutritional and behavioral interventions; and (2) explore potential effect of stress from living near toxic waste. So far, researchers have enrolled 425 mother-infant pairs and have collected blood samples, archived hair, and collected survey data.
The objective of this project is to explore the transport of iron (Fe), manganese (Mn), cadmium (Cd), and lead (Pb) from environments experienced by children to the blood and critical organs, such as the brain, heart, liver, and kidneys. Researchers seek to better understand metal exposures of children and their mothers in settings like Tar Creek by: (1) utilizing exposures during and after pregnancy, (2) using metal ions as well as complex environmental samples from Tar Creek, and (3) comparing different routes of entry from the environment into the body. Research includes an exploration of the role of toxic metals and iron status as they interact to influence metal absorption.
The objectives of this research project are to: (1) examine the effect of pre- and neonatal exposure to metals on neurochemical changes and neurobehavioral outcomes in rats; and (2) explore the potential modifying effect of stress on metals neurotoxicity.
University of Cincinnati
- Neurobehavioral Effects of Prevalent Toxicants in Children
- Early Exposure to Lead and Adult Antisocial Outcome
- Magnetic Resonance Assessment of Brain Function Altered by Lead Exposure
University of Illinois
- Developmental Effects of PCBs and Methylmercury
- Neurobehavioral Effects of PCBs and Methylmercury in Rats
Children's
Center Projects related to this topic
NCER
Research Projects related to this topic
Additional children's center research information is available on the PCB topic page.
The National Academy of Sciences has issued a recommendation to move away
from single-chemical assessments, while siting activities have raised
the issue of multiple chemical exposures. Parties are concerned not only
about what risks are associated with releases from a particular facility,
but also the potential combined effects of exposures from other sources
in the area. EPA’s research
strategy for 2000 and beyond emphasizes research on chemical mixtures.
U.S. EPA’s Supplementary
Guidance for Conducting Health Risk Assessment of Chemical Mixtures (PDF) (1.1
MB, 209pp, about PDF) (2000)
presents a number of method-specific user fact-sheets, which are intended to
provide a concise overview of each currently available mixtures risk assessment
method presented in that guidance document.
The EPA Risk Assessment Forum has published the Supplementary Guidance for
Conducting
Health Risk Assessment of Chemical
Mixtures. This document addresses only risks to human health from multichemical
exposures.
Ecological effects are beyond its scope, even though many of the procedures
might be adaptable to ecological risk assessment from multiple stressors.
Because other Agency guidelines exist that
address exposure assessment and specific toxic endpoint evaluations, this
guidance focuses on
procedures for dose-response assessment and risk characterization. The document
is available from the EPA's Office
of Water.
Brain JD, Heilig E, Donaghey TC, Knutson MD, Wessling-Resnick M, Molina RM. 2006. Effects of iron status on transpulmonary transport and tissue distribution of Mn and Fe. American Journal of Respiratory Cell and Molecular Biology 34:330-337. Abstract | PubMed
Wright RO, Amarasiriwardena C, Woolf AD, Jim R, Bellinger DC. 2006. Neuropsychological correlates of hair arsenic, manganese, and cadmium levels in school-age children residing near a hazardous waste site. Neurotoxicology 27:210-216. Abstract | PubMed
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