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Review of the U.S. Army's Health Risk Assessments for Oral Exposure to Six Chemical-Warfare Agents
tive study (Sasser et al. 1989a) in which the highest oral dose of lewisite did not produce forestomach lesions (necrosis and hyperplasia) in rats. In that study, male and female rats were intragastrically intubated with lewisite for 5 days per week for 13 weeks. Female rats were also dosed for 7 days per week during the 3-week gestation period and 4 days per week during the 3-week lactation period. The highest no-observed-adverse-effect level (NOAEL) for lewisite was 0.6 mg/kg per day. Because of the discontinuous exposure regimen, ORNL adjusted the NOAEL (NOAELadj) to a time-weighted average. That adjustment was done by calculating the total dose administered during the different exposure protocols:
0.6 mg/kg per day × (5/7) = 0.43 mg/kg per day for 13 weeks.
0.6 mg/kg per day × (7/7) = 0.6 mg/kg per day for 3 weeks.
0.6 mg/kg per day × (4/7) = 0.34 mg/kg per day for 3 weeks.
Using those values, ORNL calculated the NOAELadj to be 0.44 mg/kg per day as follows:
The RfD for lewisite was calculated to be 1 × 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.
The subcommittee is aware that the interim RfD for lewisite was reviewed by the Material/Chemical Risk Assessment (MCRA) Working Group of the Environmental Risk Assessment Program, which represents multiagency (U.S. Environmental Protection Agency (EPA), Department of Defense, and Department of Energy) expertise in deriving and validating toxicity values. The MCRA Working Group concluded that the forestomach lesions appeared to be an artifact of administering doses of lewisite directly to the forestomach in a short period of time and that the overall data base for lewisite was poor. Its consensus was that the RfD for lewisite be considered unverifiable due to data deficiencies. For those reasons and because it also considered lewisite to degrade to inor-