In this report, the Subcommittee on Chronic Reference Doses for Selected Chemical-Warfare Agents of the National Research Council's (NRC's) Committee on Toxicology reviews the scientific validity of the Army's interim values for the six chemical-warfare agents—GA, GB, GD, VX, sulfur mustard, and lewisite. The NRC report is intended to be useful to the Army in making site-specific cleanup decisions.

Contents

• Subcommittee on Chronic Reference Doses for Selected Chemical-Warfare Agents
• Committee on Toxicology
• Board on Environmental Studies and Toxicology
• Commission on Life Sciences
• Other Reports of the Board on Environmental Studies and Toxicology
• Other Reports of the Committee on Toxicology
• Preface
• Summary
• 1. Introduction
• 2. Derivation of Reference Doses
  • Reference-Dose Calculation
  • Benchmark Dose
  • Uncertainty Factors
  • Conclusions
  • References
• 3. Evaluation of the Army's Interim Reference Dose for GA
  • Derivation of the Army's Interim RFD
  • Appropriateness of the Critical Study
  • Appropriateness Of Critical End Point
  • Appropriateness Of Uncertainty Factors
  • Summary
  • Weight and Strength of Evidence
  • Conclusions
  • Data Gaps and Research Recommendations
  • References
• 4. Evaluation of the Army's Interim Reference Dose for GB
  • Derivation of the Army's Interim RfD
  • Appropriateness of the Critical Study
  • Appropriateness of Critical end Point
  • Appropriateness of Uncertainty Factors
  • Weight and Strength of Evidence
  • Conclusions
  • Data Gaps and Research Recommendations
  • References
• 5. Evaluation of the Army's Interim Reference Dose for GD
  • Derivation of the Army's Interim RfD
  • Appropriateness of the Critical Study
  • Appropriateness of Critical End Point
  • Appropriateness of Uncertainty Factors
  • Weight and Strength of Evidence
  • Conclusions
  • Data Gaps and Research Recommendations
  • References
• 6. Evaluation of the Army's Interim Reference Dose for VX
  • Derivation of the Army's Interim RfD
  • Appropriateness of the Critical Study
  • Appropriateness of Critical End Point
  • Appropriateness of Uncertainty Factors
  • Weight and Strength of Evidence
  • Conclusions
  • Data Gaps and Research Recommendations
  • References
• 7. Evaluation of the Army's Interim Reference Dose and Slope Factor For Sulfur Mustard
  • Evaluation of the Army's Interim RfD
  • Evaluation of the Army's Interim Cancer Slope Factor
  • Conclusions
  • Data Gaps and Research Recommendations
  • References
• 8. Evaluation of the Army's Interim Reference Dose for Lewisite
  • Derivation of the Army's Interim RfD
  • Appropriateness of the Critical Study
  • Appropriateness of Critical End Point
  • Appropriateness of Uncertainty Factors
  • Weight and Strength of Evidence
  • Conclusions
  • Data Gaps and Research Recommendations
  • References
• Glossary
• Appendix A Health Risk Assessment for The Nerve Agent GA
• Appendix B Health Risk Assessment for The Nerve Agent GB
• Appendix C Health Risk Assessment for The Nerve Agent GD (Soman)
• Appendix D Health Risk Assessment for The Nerve Agent VX
• Appendix E Health Risk Assessment for Sulfur Mustard (HD)
• Appendix F Health Risk Assessment for Lewisite
• Appendix G Inhibition of Cholinesterases and an Evaluation of the Methods Used to Measure Cholinesterase Activity

This project was supported by Contract Nos. DAMD 17-89-C-9086 and DAMD 17-99-C-9049 between the National Academy of Sciences and U.S. Department of Defense. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the organizations or agencies that provided support for this project.

NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.

The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Bruce Alberts is president of the National Academy of Sciences.

The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. William A. Wulf is president of the National Academy of Engineering.

The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Kenneth I. Shine is president of the Institute of Medicine.

The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy's purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Bruce M. Alberts and Dr. William A. Wulf are chairman and vice chairman, respectively, of the National Research Council.