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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8: Evaluation of the Army
8: Evaluation of the Army
Pages 83-92
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From page 83... ...
Army, Oak Ridge National Laboratory (ORNL) conducted a health risk assessment of lewisite.
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From page 84... ...
19wk = 0.44 mg/kg/day. The RfD for lewisite was calculated to be 1 x 10-4 mg/kg per day by dividing the NOAELadj by 3,000, the product of the uncertainty factors and the modifying factor selected by ORNL.
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From page 85... ...
No significant adverse effects on reproductive performance or fertility were found at any dose through two consecutive generations, nor were any other toxic effects observed. In the 90-day toxicity study (Sasser et al.
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From page 86... ...
The subcommittee disagrees with that conclusion because the statistical weakness identified appears to compromise only the detection of teratogenic effects and not necessarily the effects of mortality or marked gastric lesions that were observed in the adult female rabbits at all administered doses. Furthermore, comparisons between the results of this study and a similar teratogenicity study in rats conducted by the same investigators (Hackett et al.
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From page 87... ...
Although the possibility exists that those effects resulted from administration of lew~site directly to the stomach over a short period, resulting in an RfD that could be overprotective of noncancer health effects, there are two reasons for applying such a conservative value at this time. First, the available dose-response data are too sparse to establish conclusively that the dose-administration process primarily is responsible for the observed effects.
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From page 88... ...
EXTRAPOLATION FROM ANIMAL TO HUMAN The subcommittee believes that lewisite is a highly corrosive agent, and when it is introduced directly into the stomach in a short period, its behavior is likely to be similar across species. For that reason, the subcommittee considers the typical default value of 10 for the uncertainty factor for extrapolation of data from animals to humans (UFA)
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From page 89... ...
DATA-BASE ADEQUACY The subcommittee believes the uncertainty factor for data-base adequacy (UFD) should be assigned a value of 10 because no long-term exposure studies involving lewisite are available, only a few studies that address the acute or subchronic toxicity of lewisite are available, and little or no information about the metabolism of lewisite or its degradation products is available.
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From page 90... ...
(1987) Study UFs UFD ME Uncertainty Factor Description UFA UFH UF, NRC For animal-to-human extrapolation 3 To protect susceptible subpopulations 3 For LOAEL-to-NOAEL extrapolation For subchronic-to-chronic extrapolation For data-base adequacy Modifying factor for additional uncertainty 1 10 10 10 TOTAL UF 9,000 Abbreviations: LOAEL, lowest-observed-adverse-effect level; ME, modifying factor; NOAEL, no-observed-adverse-effect level; NRC, National Research Council; RfD, reference dose; UF, uncertainty factor CONCLUSIONS The approach used by ORNE to calculate the RfD for lewisite is consistent with the guidelines of the EPA.
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From page 91... ...
Prepared by the Eastern Research Group, Inc., Lexington, Mass., for the U.S. Environmental Protection Agency, National Center for Environmental Assessment, Washington, D.C.
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From page 92... ...
Prepared by Oak Ridge National Laboratory, Life Sciences Division, Oak Ridge, Tenn., for U.S. Depa~ent of the Army, Army Environmental Center, Aberdeen Proving Ground, Edgewood, Md.
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