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Appendix D
Critical Studies and Uncertainty Factors
Used in Developing
Acute Exposure Guideline Levels for
Chemical Warfare Agents
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TABLE D-1 Critical Studies and Uncertainty Factors Used in Developing AEGLs for GB
176
Critical Study Uncertainty Factors (UFs)
Standard and Test Temporal Intra- Inter- Total
Study End Point Severity Species Gender Duration Extrapolation species species MF UF
AEGL-1 Nondisabling Adult Female 10, 60, Cn × t =k; n = 10 1 1 10
EC50 for miosis
Mioduszewski (miosis is the first rat and 240 2; from 10 to
et al. 2000 measurable min 30 min and
change in the from 4 to 8
continuum of hours
response to
anticholinesterase
response)
AEGL-2 LOAEL for Disabling (single Human NR 10-30 Cn × t =k; n = 10 1 1 10
Baker and miosis, dyspnea, fiber electro- min 2; from 30
Sedgwick 1996 RBC-ChE myography min to all
inhibition, changes as early durations
single fiber indicator of
electromyography exposures that
changes could result in
more significant
effects)
AEGL-3 Lethal Rat Female 10, 30, Cn × t =k; n = 10 3 1 30
LC01 and LC50
Mioduszewski 60, 90, 2; from 6 to 8
et al. 2000, 240, and hours
2001, 2002 360 min
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)
a
Agent Standard Relative Potency 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 10 3 1 30
Wistar rat LC50 study
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 10 1 3 30
secondary and supportive studies
AEGL-2 and AEGL-3 VX:GB = 4 10 3 3 100
a
Based on relative potency data from GB.
Abbreviations: LC50, lethal concentration to 50% of subjects exposed; MF, modifying factor.
Source: Data obtained from NRC 2003.
177
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TABLE D-3 Critical Studies and Uncertainty Factors Used in Developing AEGLs for Sulfur Mustard
178
Critical Study Uncertainty Factors (UFs)
Test Temporal Intra- Inter- Total
Standard and Study End Point Severity Species Duration Extrapolation species species MF UF
AEGL-1 Threshold— Nondisabling Human Cn × t =k; n = 3 1 1 3
Anderson 1942 conjunctival 1
injection and
minor discomfort
with no functional
decrement
AEGL-2 LOAEL for well- Severe ocular Human Cn × t =k; n = 3 1 3a 10
Anderson 1942 marked, effects; ineffective 1
generalized military
conjunctivitis, performance
edema, photo-
phobia, and eye
irritations
AEGL-3 Lethality Mice 1 hour Cn × t =k; n = 3 3 1 10
LC50
Kumar and 3 for shorter
Vijayaraghavan periods and n
1998 = 1 for longer
periods
a
Potenial 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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APPENDIX D 179
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 (In-
dia).
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 Inter-
national Chemical Weapons Demilitarization Conference (CWD-2000), May 21-24,
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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. Edge-
wood 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.
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NRC (National Research Council). 2003. Acute Exposure Guideline Levels for Selected
Airborne Chemicals, Volume 3. Washington, DC: The National Academies Press.
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Representative terms from entire chapter:
lethal concentration