Review of the U.S. Army's Health Risk Assessments for Oral Exposure to Six Chemical-Warfare Agents (1999) / Chapter Skim
Currently Skimming:
3: Evaluation of the Army
3: Evaluation of the Army
Pages 24-35
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 24... ...
Because there was no evidence that GA is carcinogenic, a slope factor was not derived. The Army's Surgeon General accepted ORNE's proposed RfD as an interim exposure value until an independent evaluation of the proposed RfD was conducted by the National Research Council (NRC)
|
From page 25... ...
The Rf[) for GA was calculated to be 4 x 10-5 mg/kg per day by dividing the NOAELadj by 2,700, the product of the uncertainty factors and the modifying factor selected by ORNL.
|
From page 26... ...
For males, significant decreases in plasma ChE were observed in the mid- and high-dose groups at weeks I, 3, and 7 compared with control and baseline values; in addition, significant decreases were observed in the mid-dose group at weeks ~ and 13 compared with baseline but not controls values. ORNE noted that plasma-ChE values in male rats provided the least variable indicator of the lowest-observed-adverse-effect level (LOAEL)
|
From page 27... ...
The subcommittee found no oral studies that involved repeated exposure to GA and no other suitable toxicity studies for deriving the RfD for GA. Thus, the subcommittee agrees with ORNJ~ that the study by Bucci et al.
|
From page 28... ...
The NRC found no long-term health effects from short-term exposure to any specific chemical-warfare agent, but there was some evidence of an increase in malignant neoplasms among men exposed to anti-ChE agents. Although these studies are not directly applicable to deriving RfDs, they add to the completeness of the data base on GA.
|
From page 29... ...
The product of those factors was 2,700. The subcommittee evaluated each of the uncertainty factors and the modifying factor below.
|
From page 30... ...
PROTECTING SUSCEPTIBLE SUBPOPULATIONS ORNE used a factor of 10 for the uncertainty factor to protect susceptible subpopulations (UFH) because some individuals have a genetic polymorphism causing their serum-ChE activity to be abnormally low (Evans et al.
|
From page 31... ...
The subcommittee agrees that a factor of 3 is appropriate. DATA-BASE ADEQUACY As noted by ORNE, the data base on GA lacks a multigeneration reproductive toxicity study, a standard toxicity study in a second species, and toxicity studies by the oral exposure route.
|
From page 32... ...
TABLE 3-1 Uncertainty Factors Used by ORNL and the NRC to Calculate the RfD for GA Uncertainty Factor Description ORNL NRC UFA For animal-to-human extrapolation 10 10 UFH To protect susceptible subpopulations 10 10 UF, For LOAEL-to-NOAEL extrapolation 1 1 UPS For subchronic-to-chronic extrapolation 3 3 UFD For data-base adequacy 3 3 ME Modifying factor for additional uncertainty 3 3 TOTAL UF 2,700 2,700 Abbreviations: LOAEL, lowest-observed-adverse-effect level; ME, modifying factor; NOAEL, no-observed-adverse-effect level; NRC, National Research Council; ORNL, Oak Ridge National Laboratory; RfD, reference dose; and UF uncertainty factor.
|
From page 33... ...
Army Biomedical Research and Development Laboratory, Fort Detrick, Frederick, Md. Cohen, E.M., P.J.
|
From page 34... ...
Final Report. Prepared by the National Center for Toxicological Research, U.S.
|
From page 35... ...
Environmental Protection Agency, Washington, D.C. NRC (National Research Council)
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.