Appendix D
Critical Studies and Uncertainty Factors Used in Developing Acute Exposure Guideline Levels for Chemical Warfare Agents



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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, 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. 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. (May 2002). 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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