21 September 2003
Date Posted: <Posted: 07/14/2003>
Project Identification Number: BEST-K-03-05-A
Division on Earth and Life Studies
Institute of Medicine
Board on Environmental Studies and Toxicology
Board on Health Sciences Policy
A committee of the National Academies will assess the adverse health effects resulting from ingestion of perchlorate from a clinical, toxicological, medical, and public health perspective. The committee will critically evaluate the scientific literature, including both human and animal data, and will assess the key studies underlying EPA's 2002 Draft Toxicological Review and Risk Characterization for Perchlorate in terms of quality, reliability, and relevance to draw conclusions about the health implications of exposure to low levels of perchlorate in drinking water.
In conducting its assessment, the committee will first address the following basic scientific issues:
1. The current state of the science regarding potential adverse effects resulting from disruption of thyroid function in humans and laboratory animals at various stages of life. Specifically, the committee will evaluate whether science supports the model that predicts potential adverse neurodevelopmental and neoplastic effects from changes in thyroid hormone regulation resulting from disruption of iodide uptake by the thyroid gland. The committee will indicate its level of confidence in the model.
2. The levels at which chronic inhibition of iodide uptake may lead to adverse (not just adaptive) health effects in humans, especially sensitive subpopulations. The committee will consider the influence of iodine in the diet on the levels at which adverse effects would be observed, especially in sensitive subpopulations, and will indicate its degree of confidence in the levels that it proposes.
3. The levels at which changes in thyroid hormones may lead to adverse (not just adaptive) health effects in humans, especially sensitive subpopulations. The committee will indicate its confidence in these values.
The committee will evaluate the animal studies used to assess human health effects from ingestion of perchlorate with particular attention to key endpoints, including changes in brain morphometry, behavior, thyroid hormone levels, and thyroid histopathology. The committee will indicate its level of confidence in the relevance of the adverse effects observed in the animal studies to human health, especially sensitive subpopulations, and will specifically address the validity of the models that extrapolate changes in brain morphometry in rats to adverse effects in the human population, especially sensitive subpopulations. The committee will also indicate whether adverse effects, other than those associated with iodide update inhibition, may result from daily ingestion of low levels of perchlorate.
Based on the above review, the committee will determine whether EPA's findings in its 2002 Draft Toxicological Review and Risk Characterization for Perchlorate are consistent with the current scientific evidence. Specifically, the committee will determine whether EPA considered all relevant literature (both supporting and non-supporting), consistently critiqued that literature, and then used appropriate scientific studies to develop its health risk assessment. If the committee finds deficiencies in EPA's analysis, such as lack of consideration of a key study, the committee will provide suggestions as to how EPA might modify its assessment. The committee will provide a range of values consistent with scientific evidence for percent iodide uptake that would be protective of individuals at various life stages and thyroid status. The committee will also provide information on the basis of the scientific evidence that can be used to inform the selection of uncertainty factors used in the approximation of a safe lifetime exposure for humans, especially sensitive subpopulations.
As a final task, the committee will suggest specific scientific research that could reduce the uncertainty in the current understanding of human health effects associated with low-level perchlorate ingestion. Specifically, it will suggest research that could clarify safe levels of exposure for sensitive subpopulations. Rough estimates for timeframe, costs, and potential to reduce overall uncertainty will be provided for the specific research studies suggested.
The project sponsor is the Environmental Project Agency. Co-sponsorship anticipated from Department of Defense, Department of Energy, and National Aeronautics and Space Administration.
The approximate starting date for the project is 06/05/2003.
One report will be issued in approximately 15 months.
Project Duration: 15 months
Biographical sketches for the members of the NRC Committee to Assess the