Review of the U.S. Army's Health Risk Assessments for Oral Exposure to Six Chemical-Warfare Agents (1999) / Chapter Skim
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7: Evaluation of the Army
7: Evaluation of the Army
Pages 70-82
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From page 70... ...
Army, Oak Ridge National Laboratory (ORNL) conducted a health risk assessment of sulfur mustard.
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From page 71... ...
The RfD for sulfur mustard was calculated to be 7 x lo-6 mg/kg per day by dividing the L°AELa<,j by 3,000, the product of the uncertainty factors and the modifying factor selected by ORNL. APPROPRIATENESS OF THE CRITICAL STUDY The critical study used by ORNE for deriving the RfD for sulfur mustard was a two-generation reproductive study (Sasser et al.
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From page 72... ...
(1975) was an inhalation study using rats, mice, rabbits, guinea pigs, and dogs; therefore, equivalent oral doses could only be estimated from the data.
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From page 73... ...
However, that end point resulting from direct administration to the forestomach is likely to overestimate the toxicity of sulfur mustard, resulting in an RfD that might be overprotective for noncancer health effects. APPROPRIATENESS OF UNCERTAINTY FACTORS For sulfur mustard, ORNE assigned values greater than ~ to four out of five uncertainty factors and a value of ~ to the modifying factor.
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Protecting Susceptible Subpopulations The subcommittee agrees with ORNE that a factor of 10 is appropriate for the uncertainty factor to protect susceptible subpopulations (UFH)
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Moclifying Factor for Acdclitional Uncertainly The subcommittee considers the uncertainties of the data on sulfur mustard to be represented adequately by the values assigned to the uncertainty factors above and agrees with ORNE that a modifying factor (MF) of ~ is appropriate.
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In the absence of oral exposure studies, ORNE used the relative carcinogenic potency calculated by Watson et al.
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The subcommittee agrees with ORNE that calculating an SF for sulfur mustard using the relative potency approach was more appropriate than using estimates from inhalation unit risk. The subcommittee notes, however, that a recent study by CuIp et al.
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The subcommittee also used another approach to estimate the upper limit for carcinogenic potency of sulfur mustard. This approach involved evaluating the carcinogenic potency of sulfur mustard relative to its maximum tolerated dose (MTD)
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Cancer risk is estimated by multiplying the carcinogenic potency with the average lifetime daily dose. Thus, if the potential carcinogenic risk from ingestion of sulfur mustard is restricted to less than ~ x 10~5 (i in 100,000 persons)
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On the basis of available toxicity and related data on sulfur mustard, the subcommittee concludes that the Armis RfD for sulfur mustard of 7 x lo-6 mg/kg per day is scientifically valid, although the subcommittee believes that slightly different uncertainty factors should be used. The approach selected by ORNE to calculate the SF for sulfur mustard was scientifically valid given the absence of epidemiological or animal carcinogenicity studies of sulfur mustard.
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From page 81... ...
ORNL (Oak Ridge National Laboratory)
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From page 82... ...
Army Medical Research and Development Command, Fort Detrick, Frederick, Md. Watson, A.P., T.D.
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