Review of the Army's Technical Guides on Assessing and Managing Chemical Hazards to Deployed Personnel (2004)
Chapter: Appendix D Critical Studies and Uncertainty Factors Used in Developing Acute Exposure Guideline Levels for Chemical Warfare Agents
TABLE D-1 Critical Studies and Uncertainty Factors Used in Developing AEGLs for GB
|
Critical Study |
|
Uncertainty Factors (UFs) |
||||||||
|
Standard and Study |
End Point |
Severity |
Species |
Gender |
Test Duration |
Temporal Extrapolation |
Intraspecies |
Interspecies |
MF |
Total UF |
|
AEGL-1 Mioduszewski et al. 2000 |
EC50 for miosis |
Nondisabling (miosis is the first measurable change in the continuum of response to anticholinesterase response) |
Adult rat |
Female |
10, 60, and 240 min |
Cn × t =k; n = 2; from 10 to 30 min and from 4 to 8 hours |
10 |
1 |
1 |
10 |
|
AEGL-2 Baker and Sedgwick 1996 |
LOAEL for miosis, dyspnea, RBC-ChE inhibition, single fiber electromyography changes |
Disabling (single fiber electromyography changes as early indicator of exposures that could result in more significant effects) |
Human |
NR |
10-30 min |
Cn × t =k; n = 2; from 30 min to all durations |
10 |
1 |
1 |
10 |
|
AEGL-3 Mioduszewski et al. 2000, 2001, 2002 |
LC01 and LC50 |
Lethal |
Rat |
Female |
10, 30, 60, 90, 240, and 360 min |
Cn × t =k; n = 2; from 6 to 8 hours |
10 |
3 |
1 |
30 |
|
Abbreviations: EC50, effective concentration for a 50% response; LC01, lethal concentration to 1% of exposed subjects; LC50, lethal concentration to 50% of exposed subjects; MF, modifying factor; NR, not reported; RBC-ChE, red blood celll cholinesterase. Source: Data obtained from NRC 2003. |
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TABLE D-2 Relative Potency and Uncertainty Factors used in Developing AEGLs for GA, GD, GF, and VX
|
|
Uncertainty Factors (UFs) |
|||||
|
Agent |
Standard |
Relative Potencya |
Intraspecies |
Interspecies |
MF |
Total |
|
GA |
AEGL-1 and AEGL-2 |
Equivalent potency |
10 |
1 |
1 |
10 |
|
|
AEGL-3 |
GA = ½ GB potency |
10 |
3 |
1 |
30 |
|
GD |
AEGL-1 and AEGL-2 |
GD = 2 × GB potency |
10 |
1 |
1 |
10 |
|
|
AEGL-3 |
Equipotent to GB; supported by Wistar rat LC50 study |
10 |
3 |
1 |
30 |
|
GF |
AEGL-1 and AEGL-2 |
GF = 2 × GB potency |
10 |
1 |
1 |
10 |
|
|
AEGL-3 |
Equipotent to GB |
10 |
3 |
1 |
30 |
|
VX |
AEGL-1 |
VX:GB = 4; miosis data from secondary and supportive studies |
10 |
1 |
3 |
30 |
|
|
AEGL-2 and AEGL-3 |
VX:GB = 4 |
10 |
3 |
3 |
100 |
|
aBased on relative potency data from GB. Abbreviations: LC50, lethal concentration to 50% of subjects exposed; MF, modifying factor. Source: Data obtained from NRC 2003. |
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TABLE D-3 Critical Studies and Uncertainty Factors Used in Developing AEGLs for Sulfur Mustard
|
Critical Study |
|
Uncertainty Factors (UFs) |
|||||||
|
Standard and Study |
End Point |
Severity |
Species |
Test Duration |
Temporal Extrapolation |
Intraspecies |
Interspecies |
MF |
Total UF |
|
AEGL-1 Anderson 1942 |
Threshold—conjunctival injection and minor discomfort with no functional decrement |
Nondisabling |
Human |
|
Cn × t =k; n = 1 |
3 |
1 |
1 |
3 |
|
AEGL-2 Anderson 1942 |
LOAEL for well-marked, generalized conjunctivitis, edema, photophobia, and eye irritations |
Severe ocular effects; ineffective military performance |
Human |
|
Cn × t = k; n = 1 |
3 |
1 |
3a |
10 |
|
AEGL-3 Kumar and Vijayaraghavan 1998 |
LC50 |
Lethality |
Mice |
1 hour |
Cn × t =k; n = 3 for shorter periods and n = 1 for longer periods |
3 |
3 |
1 |
10 |
|
aPotenial onset of long- term ocular or respiratory effects. Abbreviations: LC50, lethal concentration to 50% of exposed subjects; LOAEL, lowest-observed- adverse-effect level; MF, modifying factor. Source: Data obtained from NRC 2003. |
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REFERENCES
Anderson, J.S. 1942. The Effect of Mustard Gas Vapour on Eyes under Indian Hot Weather Conditions. CDRE Report No. 241. Chemical Defense Research Establishment (India).
Baker, D.J., and E.M. Sedgwick. 1996. Single fibre electromyographic changes in man after organophosphate exposure. Hum. Exp. Toxicol. 15(5):369-375.
Kumar, O., and R. Vijayaraghavan. 1998. Effect of sulphur mustard inhalation exposure on some urinary variables in mice. J. Appl. Toxicol. 18(4):257-259.
Mioduszewski, R.J., J. Manthei, R. Way, D. Burnett, B. Gaviola, W. Muse, S. Thomson, D. Sommerville, and R. Crosier. 2000. Estimating the probability of sarin vapor toxicity in rats as a function of exposure concentration and duration. Proceedings of the International Chemical Weapons Demilitarization Conference (CWD-2000), May 21-24, 2000, The Hague, NL.
Mioduszewski, R.J., J. Manthei, R. Way, D. Burnett, B. Gaviola, W. Muse, J. Anthony, D. Durst, D. Sommerville, R. Crosier, S. Thomson, and C. Crouse. 2001. ECBC Low Level Operational Toxicology Program: Phase I-Inhalation Toxicity of Sarin Vapor in Rats as a Function of Exposure Concentration and Duration. ECBC-TR-183. Edgewood Research Development and Engineering Center, Aberdeen Proving Ground, MD. (August 2001).
Mioduszewski, R.J., J. Manthei, R. Way, D. Burnett, B. Gaviola, W. Muse, S. Thomson, D. Sommerville, R. Crosier, J. Scotto, D. McCaskey, C. Crouse, and K. Matson. 2002. Low-Level Sarin Vapor Exposure in Rats: Effect of Exposure Concentration and Duration on Pupil Size. ECBC-TR-235. Edgewood Chemical Biological Center, U.S. Army Soldier and Biological Chemical Command Aberdeen Proving Ground, MD. (May 2002).
NRC (National Research Council). 2003. Acute Exposure Guideline Levels for Selected Airborne Chemicals, Volume 3. Washington, DC: The National Academies Press.
