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Derivation of Reference Doses (From Review of the U.S. Army's Health Risk Assessments for Oral Exposure to Six Chemical-Warfare Agents, P 17-23, 1999, Ruth E. Crossgrove, ed., -- See NCJ-190887)

NCJ Number
190888
Editor(s)
Ruth E, Crossgrove
Date Published
1999
Length
7 pages
Annotation
This document contains a brief description of the methods used by toxicologists to derive the United States Army’s interim reference doses (RfDs) for tabun (GA), sarin (GB), soman (GD), organophosate nerve gas (VX), sulfur mustard, and lewisite.
Abstract
The RfD is an estimate (with uncertainty spanning perhaps an order of magnitude or greater) of a daily dose to the human population that is likely to be without an appreciable risk of deleterious health effects during a lifetime. The RfD process only describes the exposure conditions that are unlikely to cause noncancer health effects, which are typically assumed to have a threshold dose above which deleterious health effects would be expected to occur. The major issues in the calculation of the RfD are identifying the most sensitive effects that are relevant to the human for selecting the no-observed-adverse-effect level (NOAEL) or the lowest-observed-adverse-effect level (LOAEL), the determination of the NOAEL or LOAEL from the most appropriate study, and the magnitudes of the uncertainty factors and the modifying factor used in the process. The benchmark dose (BD) is a dose with a specified low level of excess health risk, generally in the range of 1 percent to 10 percent, that can be estimated from data with little or no extrapolation outside the experimental dose range. Multiplying several uncertainty factors together possibly can lead to a large overall uncertainty factor that results in an unnecessarily small RfD. It was concluded that the method used to derive the Army’s interim RfDs was scientifically sound and was consistent with the guidelines and process used by the Environmental Protection Agency. The BD approach should be considered in establishing RfDs in the future. Similar risk estimates from the conventional and the BD methods would provide greater confidence in the proposed RfDs. 18 references