Review of the U.S. Army's Health Risk Assessments for Oral Exposure to Six Chemical-Warfare Agents (1999) / Chapter Skim
Currently Skimming:
C: Health Risk Assessment for the Nerve Agent GD (Soman)
C: Health Risk Assessment for the Nerve Agent GD (Soman)
Pages 167-196
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 167... ...
Appendix C Health Risk Assessment for The Nerve Agent GO (Soman)
|
From page 168... ...
A small subpopulation of men and women have a genetic defect causing their blood cholinesterase activity to be abnormally low (Evans et al., 1952; HalTis and Whitaker, 19621. For homozygous individuals, the activity can be as low as 8-21% of the nonnal mean (Bonderman and Bonderrnan, 1971)
|
From page 169... ...
Prepared for Environmental Risk Assessment Program Strategic Environmental Research Development Program Prepared by Life Sciences Division OAK RIDGE NATIONAL LABORATORY* Oak Ridge, Tennessee 37831 Submitted to Material Chemical Working Group Advisory and Coordinating Committee Environmental Risk Assessment Program Strategic Environmental Research Development Program *
|
From page 170... ...
170 A~MYR/S~ASSESSME7V~SFO}~ C~EM/CA[_~ARFA~EAGEW~S Agent GO DISCLAIMER This document is an internal review draft for review purposes only and does not constitute U.S. Government policy.
|
From page 171... ...
This working group is developing toxicity values for selected chemicals of concern at federal facilities. Toxicity values will be submitted for consideration by the EPA's IRIS Consensus Process for inclusion on IRIS (EPA's Integrated Risk Information System)
|
From page 172... ...
. 2 2.2 Effect on Blood Cholinesterases 3 2.2.1 Intra- and Interspecies Variation in Blood Cholinesterase Activity 4 2.2.2 Potency of Nerve Agents as Cholinesterase Inhibitors 4 3.
|
From page 173... ...
Although the G agents are liquids under ordinary environmental conditions, their relatively high volatility and vapor pressure permits them to be disseminated in vapor form. Because of this volatility, GD is not expected to persist in soils.
|
From page 174... ...
. For some organophosphate compounds, delayed neuropathy can be induced in experimental animals at relatively low exposure levels, whereas for others the effect is only seen following exposure to supralethal doses when the animal is protected from the acute toxic effects caused by cholinesterase inhibition.
|
From page 175... ...
However, in vivo animal studies indicate a poor correlation between brain and RBC-AChE in cases of acute exposures (Jimmerson et al., 1989) , and this is reflected in the fact that blood cholinesterase activity may not always be correlated with exposure or with signs and symptoms of toxicity (Holmstedt, 1959)
|
From page 176... ...
A small subpopulation of men and women have a genetic defect causing their blood cholinesterase activity to be abnormally low (Evans et al., 1952; Harris and Whitaker, 1962)
|
From page 177... ...
3. TOXICOLOGY 3.1 Introduction Health and environmental impacts of nerve agents and related compounds (organophosphate insecticides)
|
From page 178... ...
. In addition to the immediate toxicity of the nerve agents, there is concern that exposures may lead to chronic neurological effects similar to those reported for some organophosphate insecticides.
|
From page 179... ...
. A decrease in body weight gain also occurred in female rats (75 vs 59 g decrease for high-dose and controls, respectively)
|
From page 180... ...
depression of plasma cholinesterase levels was observed in both males and females of Me highdose group during week 1 (25% and 33% for males and females, respectively) and week 7 (20% and 33% for males and females, respectively)
|
From page 181... ...
with ANOVA and Dunnett's and Scheffe's Comparisons. In the re-evaluation, RBC and plasma cholinesterase levels were compared to respective controls for the same sampling times as well as to the pre-exposure values within each group (Tables 5-8)
|
From page 182... ...
Table 6. GD-Induced RBC-AChE Inhibition in Male CD Rats (Dunnett's Comparison)
|
From page 183... ...
Table 8. GD-Induced Plasma-AChE Inhibition in Male CD Rats (Dunnett's Comparison)
|
From page 184... ...
was observed when Chinese hamster ovary cells were exposed in vitro to 200 ,ug/mL of GD. Mice treated in vivo with a maximally tolerated intraperitoneal dose of 300 fig GD/kg did not exhibit a significant increase in SCE in splenic lymphocytes.
|
From page 185... ...
. Animal data have shown that exposure to low doses of nerve agents for extended periods of time can result in low blood ChE activity levels without signs of toxicity.
|
From page 186... ...
. An uncertainty factor of 10 for sensitive subpopulations is considered necessary because some individuals have a genetic defect causing their blood cholinesterase activity to be abnormally low (Evans et al.' 1952; Harris and Whitaker, 1962)
|
From page 187... ...
In the derivation of the oral RfDs for other organophosphate compounds, the EPA has used NOAELs for cholinesterase inhibition following short-term exposures without adjustment for a more prolonged exposure period because of the unlikelihood that the endpoint would change over time (i.e., a subchronic-to-chronic UP of 1 was used)
|
From page 188... ...
188 DRAFT A~MYR/SWASSESSME}V~SFOW C~EM/CAI _WA~FA~EAGEW~S Agent GD 5. CARCINOGENIC1IY ASSESSMENT FOR GD The potential carcinogenicity of agent GD cannot be determined.
|
From page 189... ...
1951. Blood cholinesterase levels and range of personal variation in a healthy adult population.
|
From page 190... ...
U.S. Army Medical Research and Development Command, Biomedical Laboratory, Aberdeen Proving Ground, MD.
|
From page 191... ...
1992. Characterizing biological variability in livestock blood cholinesterase activity for biomonitoring organophosphate nerve agent exposure.
|
From page 192... ...
1994. Toxicity of the organophosphate chemical warfare agents GA, GB, and VX: Implications for public protection.
|
From page 193... ...
1984. Brain pathology induced by organophosphate poisoning with nerve agent soman.
|
From page 194... ...
Proc. of the Worlcshop on Convulsions and Related Brain Damage Induced by Organophosphorous Agents, ADA222912, Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground.
|
From page 195... ...
1976. Components of variability in blood cholinesterase assay results.
|
From page 196... ...
(c) in vitro Acute toxic effects in 20-30 2-4.5 humans/oral dose human oral LD50 25 50b 5 20b 5-20 (estimated)
|
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.