Acute Exposure Guideline Levels for Selected Airborne Chemicals

Volume 3

Editor: National Academies Press
ISBN: 9780309088831
eISBN Pdf: 9780309539463
eISBN Epub: 9780309168168
Lugar de publicación: Estados Unidos
Año de publicación digital: 2003
Mes: Mayo
Páginas: 516
Idioma: Ingles

Descripción

This report reviews documents on acute exposure guideline levels (AEGLs) for nerve agents GA (tabun), GB (sarin), GD (soman), GD, and VX, sulfur mustard, diborane, and methyl isocyanate. The documents were developed by the National Advisory Committee on Acute Exposure Guideline Levels for Hazardous Chemicals (NAC). The subcommittee concludes that the AEGLs developed in those documents are scientifically valid conclusions based on data reviewed by NAC and are consistent with the NRC reports on developing acute exposure guideline levels.

Acute Exposure Guideline Levels for Selected Airborne Chemicals
Copyright
OTHER REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY
Preface
Dedication
Contents
Introduction
- SUMMARY OF REPORT ON GUIDELINES FOR DEVELOPING AEGLS
- REVIEW OF AEGL REPORTS
- REFERENCES
Roster of the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances
Appendixes
- 1 Nerve Agents GA, GB, GD, GF, and VX
  - SUMMARY
    - Derivation of G-Agent AEGL Estimates
      - AEGL-1 and AEGL-2 Values for G-series Agents
        AEGL-3 Values for G-Series Agents
    - Derivation of Agent VX AEGL Estimates
    - Research Needs
      - G-Series Agents
        Agent VX
  - 1. INTRODUCTION
  - 2. HUMAN TOXICITY DATA
    - 2.1. Acute Lethality
      - G Agents
        Agent VX
      - 2.1.1. Case Reports
        Agent GB
    - 2.2. Nonlethal Toxicity
      - 2.2.1. Case Reports
        Agent GB
      - 2.2.2. Acute Studies
        Agent GB
        Agent GD
        Agent GA
        Agent VX
      - 2.2.3. Epidemiologic Studies
    - 2.3. Neurotoxicity
    - 2.4. Developmental and Reproductive Toxicity
    - 2.5. Genotoxicity
    - 2.6. Carcinogenicity
    - 2.7. Summary
      - G-series Agents
        Agent VX
  - 3. ANIMAL TOXICITY DATA
    - 3.1. Acute Lethality
      - 3.1.1. Nonhuman Primates
        Agent GB
        Agent GA
        Agent GD
      - 3.1.2. Dogs
        Agent GB
        Agent GA
        Agent VX
      - 3.1.3. Rats
        Agent GB
        Agent GA
        Agent GD
        Agent GF
        Agent VX
      - 3.1.4. Mice
        Agent GB
        Agent GD
        Agent GF
        Agent VX
      - 3.1.5. Guinea pigs
        Agent GB
        Agent GD
        Agent VX
      - 3.1.6. Rabbits
        Agent GB
        Agent GA
        Agent VX
      - 3.1.7. Cats
      - 3.1.8. Goats
        Agent VX
      - 3.1.9. Hamsters
        Agent VX
      - 3.1.10. Summary of Acute Lethality Data in Animals
    - 3.2. Nonlethal Toxicity
      - 3.2.1. Nonhuman Primates
        Agent GB
        Agent GD
      - 3.2.2. Dogs
        Agent GB
      - 3.2.3. Rats
        Agent GB
        Agent GD
        Agent GF
        Agent VX
      - 3.2.4. Mice
        Agent GB
        Agent VX
      - 3.2.5. Guinea pigs
        Agent GB
        Agent GD
        Agent VX
      - 3.2.6. Rabbits
        Agent VX
      - 3.2.7. Summary of Nonlethal Toxicity in Animals
    - 3.3. Neurotoxicity
    - 3.4. Developmental and Reproductive Effects
      - 3.4.1. Rats
        Agent GB
        Agent GA
        Agent GD
        Agent VX
      - 3.4.2. Guinea Pigs
      - 3.4.3. Rabbits
        Agent GB
        Agent GA
        Agent GD
        Agent VX
      - 3.4.4. Sheep
        Agent VX
      - 3.4.5. Summary
    - 3.5. Genotoxicity
      - Agent GB
        Agent GA
        Agent VX
        Summary
    - 3.6. Carcinogenicity
      - Agent GB
        Agent GA
        Agent VX
        Summary
    - 3.7. Summary
      - G Agents
        Agent VX
  - 4. SPECIAL CONSIDERATIONS
    - 4.1. Metabolism, Toxicokinetics, and Disposition
      - 4.1.1. Absorption
      - 4.1.2. Toxicokinetics
      - 4.1.3. Disposition and Metabolism
      - 4.1.4. Distribution and Excretion
    - 4.2. Mechanism of Toxicity
    - 4.3. Relative Toxic Potency
      - 4.3.1. In Vitro Potency
      - 4.3.2. In Vivo Potency
        G Agents
        Agent VX
        Human Estimates ofGB and VX Toxicity
      - 4.3.3. Comparison of Exposure Standards
        G-Series Agents
        Agent VX
      - 4.3.4. Selection of Nerve Agent Potency Values for Use in Deriving AEGLs
        G Agents
        Agent VX
    - 4.4. Structure-Activity Relationships
    - 4.5. Other Relevant Information
      - 4.5.1. Breathing Rates and Toxicity
      - 4.5.2. Delayed Neuropathy
        G Agents
        Agent VX
      - 4.5.3. Intra- and Interspecies Variability in Esterase Activity and Response to Nerve Agents
        Intraspecies Variability
        Interspecies Variability
        G-series Agents
        Agent VX
      - 4.5.4. Unique Physicochemical Properties
      - 4.5.5. Concurrent Exposure Issues
        Multiple Exposures to Similar Chemicals
        Multiple Exposure Through Different Exposure Pathways
      - 4.5.6. Critical Effect End Point
  - 5. DATA ANALYSIS FOR AEGL-1
    - 5.1. Summary of Human Data Relevant to AEGL-1
      - G-Series Agents
        Agent VX
    - 5.2. Summary of Animal Data Relevant to AEGL-1
      - G-Series Agents
        Agent VX
    - 5.3. Derivation of AEGL-1 for Agent GB
      - Derivation of AEGL-1 Values Using Animal Data
    - 5.4. Derivation of AEGL-1 Values for Agents GA, GD, and GF
    - 5.5. Derivation of AEGL-1 for Agent VX
  - 6. DATA ANALYSIS FOR AEGL-2
    - 6.1. Summary of Human Data Relevant to AEGL-2
    - 6.2. Summary of Animal Data Relevant to AEGL-2
    - 6.3. Derivation of AEGL-2 for Agent GB
    - 6.4. Derivation of AEGL-2 Values for Agents GA, GD, and GF
    - 6.5. Derivation of AEGL-2 Values for Agent VX
  - 7. DATA ANALYSIS FOR AEGL-3
    - 7.1. Summary of Human Data Relevant to AEGL-3
    - 7.2. Summary of Animal Data Relevant to AEGL-3
      - Agent GB
        Agent GD
        Agent GF
    - 7.3. Derivation of AEGL-3 for Agents GB and GD
      - Agent GB
        Benchmark Exposure Analyses
        Agent GD
    - 7.4. Derivation of AEGL-3 Values for Agents GA and GF
    - 7.5. Derivation of AEGL-3 Values for Agent VX
  - 8. SUMMARY OF AEGLS
    - 8.1. AEGL Values and Toxicity End Points
      - G-Series Agents
        Agent VX
    - 8.2. Comparison with other Standards and Criteria
      - G Agents
        Agent VX
    - 8.3. Data Adequacy and Research Needs
      - G Agents
        Agent VX
  - 9. REFERENCES
  - Appendixes
  - APPENDIX A DERIVATION OF AEGL VALUES
    - Derivation of AEGL-1
    - Derivation of AEGL-1 for Agent GB (Sarin) from Human Data Set
    - Derivation of AEGL-2 for Agent GB (Sarin)
    - Derivation of AEGL-3 for Agent GB (Sarin)
    - Derivation of AEGL-3 for Agent GD (Alternate Estimate)
    - Derivation of AEGL-1 for Agent VX Vapor from Agent GB Toxicity Data
    - Derivation of AEGL-2 for Agent VX Vapor from Agent GB Toxicity Data
    - Derivation of AEGL-3 for Agent VX Vapor from Agent GB Toxicity Data
  - APPENDIX B Concentration-Time Curve for Sarin-Induced Miosis in Humans and Lethality in SD Rats
  - APPENDIX C Benchmark Exposure Analysis of GB Vapor Lethality Data for Female SD Rats
  - APPENDIX D DERIVATION SUMMARY FOR ACUTE EXPOSURE GUIDELINE LEVELS FOR NERVE AGENTS
    - Derivation Summary For Agent GA (CAS No. 77–81–6) (Tabun; Dimethylamidocyanophosphate)
    - Derivation Summary for Agent GB (CAS No. 107–44–8) (Sarin; Isopropylmethylphosphonofluoridate)
    - Derivation Summary for Agent GD (CAS No. 96–64–0) (Soman; Pinacolyl Methylphosphonofluoridate)
    - Derivation Summary for Agent GF (CAS No. 329–99–7) (O-cyclohexyl-methlyfluorophosphonate)
    - Derivation Summary for Agent VX Vapor (CAS No. 50782–69–9) (O-Ethyl-S-(Isopropyl-Aminoethyl)Methyl P ...
- 2 Sulfur Mustard (Agent HD)
  - SUMMARY
  - I. INTRODUCTION
  - 2. HUMAN TOXICITY DATA
    - 2.1. Acute Lethality
    - 2.2. Nonlethal Toxicity
      - 2.2.1. Epidemiologic Studies
    - 2.3. Neurotoxicity
    - 2.4. Developmental and Reproductive Toxicity
    - 2.5. Genotoxicity
    - 2.6. Carcinogenicity
    - 2.7. Summary
  - 3. ANIMAL TOXICITY DATA
    - 3.1. Acute Lethality
      - 3.1.1. Rats
      - 3.1.2 Mice
      - 3.1.3. Guinea pigs
    - 3.2. Nonlethal Toxicity
      - 3.2.1. Dogs
      - 3.2.2. Rats
      - 3.2.3. Mice
      - 3.2.4. Rabbits
      - 3.2.5. Guinea pigs
    - 3.3. Neurotoxicity
    - 3.4. Developmental and Reproductive Toxicity
    - 3.5. Genotoxicity
    - 3.6. Chronic Toxicity and Carcinogenicity
    - 3.7. Summary
  - 4. SPECIAL CONSIDERATIONS
    - 4.1. Metabolism and Disposition
    - 4.2. Mechanism of Toxicity
    - 4.3. Structure-Activity Relationships
    - 4.4. Other Relevant Information
      - 4.4.1. Species Variability
  - 5. DATA ANALYSIS FOR AEGL-1
    - 5.1. Summary of Human Data Relevant to AEGL-1
  - 5.2. SUMMARY OF ANIMAL DATA RELEVANT TO AEGL-1
    - 5.3. Derivation of AEGL-1
  - 6. DATA ANALYSIS FOR AEGL-2
    - 6.1. Summary of Human Data Relevant to AEGL-2
    - 6.2. Summary of Animal Data Relevant to AEGL-2
    - 6.3. Derivation of AEGL-2
  - 7. DATA ANALYSIS FOR AEGL-3
    - 7.1. Summary of Human Data Relevant to AEGL-3
    - 7.2. Summary of Animal Data Relevant to AEGL-3
    - 7.3. Derivation of AEGL-3
  - 8. SUMMARY OF AEGLS
    - 8.1. AEGL Values and Toxicity End Points
    - 8.2. Comparison with Other Standards and Guidelines
    - 8.3. Data Adequacy and Research Needs
  - 9. REFERENCES
  - Appendixes
  - APPENDIX A Derivations of AEGL Values
    - Derivation of AEGL-1
    - Derivation of AEGL-2
    - Derivation of AEGL-3
  - APPENDIX B Determination of Temporal Scaling Factor (n) for AEGL Derivations
  - APPENDIX C Carcinogenicity Assessment for Acute Exposure to Sulfur Mustard (Agent HD)
  - APPENDIX D
    - Sulfur Mustard (CAS NO. 505–60–2)
- 3 Methyl Isocyanate
  - SUMMARY
  - 1. INTRODUCTION
  - 2. HUMAN TOXICITY DATA
    - 2.1. Bhopal Disaster
    - 2.2. Nonlethal Toxicity
      - 2.2.1. Case Reports
      - 2.2.2. Experimental Studies
    - 2.3. Developmental and Reproductive Toxicity
    - 2.4. Genotoxicity
    - 2.5. Carcinogenicity
    - 2.6. Summary
  - 3. ANIMAL TOXICITY DATA
    - 3.1. Acute Lethality
    - 3.1.1. Rabbits
      - 3.1.2. Guinea Pigs
      - 3.1.3. Rats
      - 3.1.4. Mice
    - 3.2. Nonlethal Toxicity
      - 3.2.1. Guinea Pigs
      - 3.2.2. Rats
      - 3.2.3. Mice
    - 3.3. Developmental and Reproductive Toxicity
    - 3.4. Genotoxicity
    - 3.5. Chronic Toxicity and Carcinogenicity
    - 3.6. Summary
  - 4. SPECIAL CONSIDERATIONS
    - 4.1. Metabolism and Disposition
    - 4.2. Mechanism of Toxicity
    - 4.3. Other Relevant Information
      - 4.3.1. Species Variability
      - 4.3.2. Concentration-Exposure Duration Relationship
  - 5. DATA ANALYSIS FOR AEGL-1
    - 5.1. Summary of Human Data Relevant to AEGL-1
    - 5.2. Summary of Animal Data Relevant to AEGL-1
    - 5.3. Derivation of AEGL-1
  - 6. DATA ANALYSIS FOR AEGL-2
    - 6.1. Summary of Human Data Relevant to AEGL-2
    - 6.2. Summary of Animal Data Relevant to AEGL-2
    - 6.3. Derivation of AEGL-2
  - 7. DATA ANALYSIS FOR AEGL-3
    - 7.1. Summary of Human Data Relevant to AEGL-3
    - 7.2. Summary of Animal Data Relevant to AEGL-3
    - 7.3. Derivation of AEGL-3
  - 8. SUMMARY OF AEGLS
    - 8.1. AEGL Values and Toxicity End Points
    - 8.2. Comparison with Other Standards and Criteria
    - 8.3. Data Adequacy and Research Needs
  - 9. REFERENCES
  - Appendixes
  - APPENDIX A Time-Scaling Calculations
  - APPENDIX B Derivation of AEGL Values
    - Derivation of AEGL-1
    - Derivation of AEGL-2
    - Derivation of AEGL-3
  - APPENDIX C DERIVATION SUMMARY FOR ACUTE EXPOSURE GUIDELINE LEVELS FOR METHYL ISOCYANATE (CAS No. 62...
  - APPENDIX D CATEGORY PLOT FOR METHYL ISOCYANATE
- 4 Diborane
  - SUMMARY
  - 1. INTRODUCTION
  - 2. HUMAN TOXICITY DATA
    - 2.1. Acute Lethality
    - 2.2. Nonlethal Toxicity
      - 2.2.1. Case Reports
    - 2.2.2. Epidemiology Studies
      - 2.2.3. Other
    - 2.3. Developmental and Reproductive Effects
    - 2.4. Genotoxicity
    - 2.5. Carcinogenicity
    - 2.6. Summary
  - 3. ANIMAL TOXICITY DATA
    - 3.1. Acute Lethality
      - 3.1.1. Dogs
      - 3.1.2. Rats
      - 3.1.3. Mice
      - 3.1.4. Rabbits
      - 3.1.5. Hamsters
    - 3.2. Nonlethal Toxicity
      - 3.2.1. Dogs
      - 3.2.2. Rats
      - 3.2.3. Mice
      - 3.2.4. Guinea pigs
    - 3.3. Developmental and Reproductive Effects
    - 3.4. Genotoxicity
    - 3.5. Carcinogenicity
    - 3.6. Summary
  - 4. SPECIAL CONSIDERATIONS
    - 4.1. Metabolism and Disposition
    - 4.2. Mechanism of Toxicity
    - 4.3. Structure-Activity Relationships
    - 4.4. Other Relevant Information
      - 4.4.1. Species Variability
      - 4.4.2. Confounding Factors
      - 4.4.3. Concentration-Exposure Duration Relationship
  - 5. DATA ANALYSIS FOR AEGL-1
    - 5.1. Human Data Relevant to AEGL-1
    - 5.2. Animal Data Relevant to AEGL-1
    - 5.3. Derivation of AEGL-1
  - 6. DATA ANALYSIS FOR AEGL-2
    - 6.1. Human Data Relevant to AEGL-2
    - 6.2. Animal Data Relevant to AEGL-2
    - 6.3. Derivation of AEGL-2
  - 7. DATA ANALYSIS FOR AEGL-3
    - 7.1. Human Data Relevant to AEGL-3
    - 7.2. Animal Data Relevant to AEGL-3
    - 7.3. Derivation of AEGL-3
  - 8. SUMMARY OF AEGLS
    - 8.1. AEGL Values and Toxicity End Points
    - 8.2. Comparisons with Other Standards and Guidelines
    - 8.3. Data Adequacy and Research Needs
  - 9. REFERENCES
  - Appendixes
  - APPENDIX A Derivation of AEGL Values
    - Derivation of AEGL-1
    - Derivation of AEGL-2
  - DERIVATION OF AEGL-3
  - APPENDIX B Time Scaling Calculations
  - APPENDIX C