Review of the U.S. Army's Health Risk Assessments for Oral Exposure to Six Chemical-Warfare Agents (1999) / Chapter Skim
Currently Skimming:
6: Evaluation of the Army
6: Evaluation of the Army
Pages 59-69
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 59... ...
The Armis Surgeon General accepted ORNt'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 60... ...
to yield a dose of 0.06,ug/kg per day. The RfD for VX was calculated to be 6 x 10-7 mg/kg per day by dividing the adjusted LOAEL by 90, the product of the uncertainty factors and the modifying factor selected by ORNL.
|
From page 61... ...
. The subcommittee believes that it would be useful to review the raw data from the study to determine whether animal weight might explain an appreciable amount of the residual variance in ChE concentrations.
|
From page 62... ...
The subcommittee notes that ChE inhibition is typically considered a biomarker of exposure to organophosphate agents rather than an adverse effect. However, it is generally agreed that inhibition of RBC and plasma ChE contributes to the overall hazard identification of ChE-inhibiting agents.
|
From page 63... ...
Data summaries from human experimentation conducted in the 1950s and 1960s were evaluated by the NRC in a series of reports titled Possible Long-Term Health Effects of Short-Term Exposure to ChemicaZAgents (NRC 1982, 1984, 19853. The reports include an evaluation of health records of volunteer soldiers who were exposed intravenously or intramuscularly to chemical-warfare agents, as well as a follow-up morbidity study conducted by the NRC in 1985.
|
From page 64... ...
EXTRAPOLATION FROM LOAEL TO NOAEL The subcommittee assigned a factor of 10 to the uncertainty factor for extrapolation from a LOAEL to a NOAEL (UFI) because the 60% inhibition of ChE observed with the LOAEL was near levels where physical signs of clinical toxicity might occur.
|
From page 65... ...
to account for the absence of longterm oral studies of VX in humans or a relevant animal model. MODIFYING FACTOR FOR ADDITIONAL UNCERTAINTY The subcommittee considers the uncertainties of the data on VX to be represented adequately by the values assigned to the uncertainty factors above and believes a modifying factor (MF)
|
From page 66... ...
(1964) Study Uncertainty Factor Description NRC UFA For animal-to-human extrapolation 1 UFH To protect susceptible subpopulations 10 UF, For LOAEL-to-NOAEL extrapolation 10 UPS For subchronic-to-chronic extrapolation 10 UFD For data-base adequacy 3 ME Modifying factor for additional uncertainty 1 TOTAL UF 3,000 Abbreviations: LOAEL' lowest-observed-adverse-effect level; MF' modifying factor; NOAEL, no-observed-adverse-effect level; NRC, National Research Council; RfD, reference dose; UF, uncertainty factor inhibition in humans, because 60% ChE inhibition was observed at that dose and lower doses were not tested.
|
From page 67... ...
U.S. Army Medical Research and Development Command, Biomedical Laboratory, Aberdeen Proving Ground, Edgewood, Md.
|
From page 68... ...
Washington, D.C.: National Academy Press. NRC (National Research Council)
|
From page 69... ...
1964. Tolerance of Han to Uncontaminated Water Technical Report C-LR 3231.
|
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.