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Use of arsenic-73 in research supports USEPA's regulatory decisions on inorganic arsenic in drinking water*
Citation:
HUGHES, M. F., D. J. THOMAS, AND M. STYBLO. Use of arsenic-73 in research supports USEPA's regulatory decisions on inorganic arsenic in drinking water*. Presented at Workshop on the Nation's needs for Isotopes: Present and Future, Rockville, MD, August 05 - 07, 2008.
Impact/Purpose:
Because the Agency is charged to review the inorganic arsenic drinking water standard every 5-6 years, the continued availability of 73As is vital to performance of research needed to protect the public's health.
Description:
Inorganic arsenic is a natural contaminant of drinking water in the United States and throughout the world. Long term exposure to inorganic arsenic in drinking water at elevated levels (>100 ug/L) is associated with development of cancer in several organs, cardiovascular disease, diabetes, keratoses and other diseases. Under the aegis of the Safe Drinking Water Act Amendments of 1996, the U.S. EPA lowered the arsenic drinking water standard from 50 to 10 ug/L and has undertaken a laboratory-based research program to reduce uncertainties in the risk assessment for arsenic. An integral part of this research program has been studies of the metabolism and disposition of arsenic that use the radionuc1ide, 73As. This radionuc1ide has played a critical role in studies of the metabolism and disposition of arsenic at molecular, cellular, and whole animal levels of complexity. For example, availability of 73As greatly facilitated the purification ofthe enzyme that catalyzes the methylation ofarsenic and is used in studies of the arsenic methylation with recombinant human and rat arsenic methyltransferase. In studies with cultured cells, 73As has been used to study interspecies and intraspecies variability in capacity to methylate inorganic arsenic. Coupled with analytical tools for the speciation of 73As-labeled metabolites, these studies have formed the basis for new insights into the genetic basis of differences in arsenic methylation capacity. Studies of arsenic metabolism and retention in mice have greatly benefitted from the availability of 73As. Using a whole body counter to detect and quantify arsenic in mice, 73As has been used in a variety of studies on the dosage dependence of arsenic retention and metabolism in the mouse. These studies are the foundation for a physiologically based pharmacokinetic model for arsenic in the mouse. Recently, 73As has been used in the phenotypic characterization of arsenic metabolism and retention in mice genetically modified to lack the ca~acity to convert inorganic arsenic into its methylated metabolites. In sum, availability of 3As has materially aided the US EPA in development of a body of information that supports its regulatory decisions concerning arsenic in drinking water. Because the Agency is charged to review the inorganic arsenic drinking water standard every 5-6 years, the continued availability of 73As is vital to performance of research needed to protect the public's health. (This abstract does not represent U.S. EPA policy.)