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RE-EVALUATION OF DRINKING-WATER GUIDELINES FOR DIISOPROPYL METHYLPHOSPHONATE Executive Summary DIISOPROPYL METHYLPHOSPHONATE (DIMP) is a groundwater contaminant at the U.S. Army's Rocky Mountain Arsenal in Colorado. DIMP is a chemical by-product resulting from the manufacture and detoxification of the nerve agent GB (Sarin), which was produced at the arsenal from 1953 to 1957. For some time, there has been disagreement between the Army and the State of Colorado regarding the appropriate drinking-water contaminant guideline for DIMP. In 1989, the U.S. Environmental Protection Agency (EPA) established a drinking-water guideline of 600 micrograms per liter (µg/L), but the State of Colorado promulgated a lower guideline of 8 µg/L. The reason for the difference is that different studies were used to calculate the guidelines. Colorado used one-generation reproductive toxicity study in mink, whereas EPA used a subchronic toxicity study in dogs. EPA did not use the mink study, which reported an increase in female mortality, citing natural high mortality in captive mink and uncertainties about the relevance of mink to human health assessment. Colorado disagreed with EPA's assessment, contending that EPA used inappropriate data to assess mortality rates in captive mink and that mink have extrapolative relevance to humans. To help resolve the disagreement, a two-generation reproductive study in mink was conducted. The Army asked the National Research Council (NRC) for an independent evaluation of that 1997 study and a re-evaluation of the drinking-water guideline for DIMP. The NRC as
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RE-EVALUATION OF DRINKING-WATER GUIDELINES FOR DIISOPROPYL METHYLPHOSPHONATE signed this task to the Committee on Toxicology, which convened the Subcommittee on the Toxicity of Diisopropyl Methylphosphonate, a multidisciplinary group of experts. The subcommittee evaluated the two-generation reproductive study, as well as other studies relevant to assessing the toxicity of DIMP. Of particular relevance were a subchronic toxicity study in mink and a comparative metabolism study in mink and rats. Data on the use of mink as a predictive model in toxicology also were reviewed. The subcommittee evaluated the biology and physiology of mink and found no scientific basis to preclude the use of mink in quantitative human-health risk assessments. In fact, the weight of evidence on DIMP indicates that two studies in mink—the two-generation reproductive toxicity study and the subchronic toxicity study—provide the most appropriate database for deriving a drinking-water guideline for DIMP. The subcommittee concludes that neither EPA's nor Colorado's drinking-water guideline for DIMP is based on the best currently available data. The subcommittee considers the 1997 two-generation reproductive study to be the best available study for deriving a drinking-water guideline, because it involved the most relevant exposure duration (13 months) and because the most biologically meaningful findings of the study, Heinz body formation (protein aggregates in oxidatively-stressed red blood cells) and cholinesterase (ChE) inhibition, are consistent with the results of the subchronic toxicity study in mink.
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