Acute exposure guideline levels for selected airborne chemicals / Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission of Life Sciences, National Research Council.

Format:

Book

Author/Creator:

National Research Council (U.S.), Subcommittee on Acute Exposure Guideline Levels Staff, Corporate Author.

Contributor:

National Research Council (U.S.). Subcommittee on Acute Exposure Guideline Levels.

Series:

Compass series (Washington, D.C.)

The compass series

Language:

English

Subjects (All):

Gases, Asphyxiating and poisonous.

Hazardous substances--Environmental aspects.

Hazardous substances.

Hazardous substances--Health aspects.

Chemicals--Physiological effect.

Chemicals.

Chemicals--Health aspects.

Physical Description:

1 online resource (515 p.)

Edition:

1st ed.

Place of Publication:

Washington, D.C. : National Academy Press, c2003.

Language Note:

English

Summary:

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.

Contents:

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

2.1.1. Case Reports

Agent GB

2.2. Nonlethal Toxicity

2.2.1. Case Reports

2.2.2. Acute Studies

Agent GD

Agent GA

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

3. ANIMAL TOXICITY DATA

3.1. Acute Lethality

3.1.1. Nonhuman Primates

3.1.2. Dogs

3.1.3. Rats

Agent GF

3.1.4. Mice

3.1.5. Guinea pigs

3.1.6. Rabbits

3.1.7. Cats

3.1.8. Goats

3.1.9. Hamsters

3.1.10. Summary of Acute Lethality Data in Animals

3.2. Nonlethal Toxicity

3.2.1. Nonhuman Primates

3.2.2. Dogs

3.2.3. Rats

3.2.4. Mice

Agent GB.

Agent VX

3.2.5. Guinea pigs

3.2.6. Rabbits

3.2.7. Summary of Nonlethal Toxicity in Animals

3.3. Neurotoxicity

3.4. Developmental and Reproductive Effects

3.4.1. Rats

3.4.2. Guinea Pigs

3.4.3. Rabbits

3.4.4. Sheep

3.4.5. Summary

3.5. Genotoxicity

Summary

3.6. Carcinogenicity

3.7. Summary

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

Human Estimates ofGB and VX Toxicity

4.3.3. Comparison of Exposure Standards

4.3.4. Selection of Nerve Agent Potency Values for Use in Deriving AEGLs

4.4. Structure-Activity Relationships

4.5. Other Relevant Information

4.5.1. Breathing Rates and Toxicity

4.5.2. Delayed Neuropathy

4.5.3. Intra- and Interspecies Variability in Esterase Activity and Response to Nerve Agents

Intraspecies Variability

Interspecies Variability

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

5.2. Summary of Animal Data Relevant to AEGL-1.

G-Series Agents

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

7.3. Derivation of AEGL-3 for Agents GB and GD

Benchmark Exposure Analyses

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

8.2. Comparison with other Standards and Criteria

8.3. Data Adequacy and Research Needs

9. REFERENCES

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)

I. INTRODUCTION

2.2.1. Epidemiologic Studies

3.1.1. Rats

3.1.2 Mice

3.1.3. Guinea pigs

3.2.1. Dogs

3.2.2. Rats

3.2.3. Mice

3.2.4. Rabbits

3.4. Developmental and Reproductive Toxicity

3.6. Chronic Toxicity and Carcinogenicity

4.1. Metabolism and Disposition

4.3. Structure-Activity Relationships

4.4. Other Relevant Information

4.4.1. Species Variability

5.2. SUMMARY OF ANIMAL DATA RELEVANT TO AEGL-1

5.3. Derivation of AEGL-1

6.3. Derivation of AEGL-2

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

8.2. Comparison with Other Standards and Guidelines

APPENDIX A Derivations of AEGL Values

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

2.1. Bhopal Disaster

2.2.2. Experimental Studies

2.3. Developmental and Reproductive Toxicity

2.4. Genotoxicity

2.5. Carcinogenicity

2.6. Summary

3.1.1. Rabbits

3.1.2. Guinea Pigs

3.2.1. Guinea Pigs

3.3. Developmental and Reproductive Toxicity

3.4. Genotoxicity

3.5. Chronic Toxicity and Carcinogenicity

3.6. Summary

4.3. Other Relevant Information

4.3.1. Species Variability

4.3.2. Concentration-Exposure Duration Relationship

5.2. Summary of Animal Data Relevant to AEGL-1

7.2. Summary of Animal Data Relevant to AEGL-3.

Notes:

Bibliographic Level Mode of Issuance: Monograph

Includes bibliographical references.

ISBN:

0-309-16816-3

1-280-17995-3

9786610179954

0-309-53946-3

OCLC:

794856158