SULFUR MUSTARD (AGENT HD) CAS Reg. No. 505-60-2 PROPOSED

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ACUTE EXPOSURE GUIDELINE LEVELS (AEGLs)

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2053

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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

2000

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TABLE OF CONTENTS

PREFACE . ii

LIST OF TABLES v

EXECUTIVE SUMMARY . vi

1. INTRODUCTION . 1

2. HUMAN TOXICITY DATA . 1

2.1 Acute Lethality 1

2.2 Nonlethal Toxicity . 2

2.3 Epidemiologic Studies 9

2.4 Developmental/Reproductive Toxicity 9

2.5 Genotoxicity 11

2.6 Carcinogenicity 12

2.7 Summary . 15

3. ANIMAL TOXICITY DATA . 15

3.1 Acute Lethality . 15

3.1.1 Rats 15

3.1.2 Mice 15

3.1.3 Guinea pigs . 16

3.1.4 Summary of Acute Lethality in Animals 17

3.2 Nonlethal Toxicity . 17

3.2.1. Dogs . 17

3.2.2. Rats 18

3.2.3. Mice 19

3.2.4. Rabbits 20

3.2.5. Guinea Pigs . 21

3.2.6. Summary of Nonlethal Toxicity Data in Animals 22

3.3 Developmental/Reproductive Toxicity . 22

3.4 Genotoxicity 22

3.5 Carcinogenicity 22

4. SPECIAL CONSIDERATIONS 24

4.1 Metabolism and Disposition . 24

4.2 Mechanism of Toxicity . 25

4.3 Structure-Activity Relationships . 26

4.4 Other Relevant Information . 27

4.4.1 Species Variability . 27

4.4.2 Concurrent Exposure Issues 27

TABLE OF CONTENTS (Continued)

5. RATIONALE AND PROPOSED AEGL-1 27

5.1 Summary of Human Data Relevant to AEGL-1 . 27

5.2 Summary of Animal Data Relevant to AEGL-1 28

5.3 Derivation of AEGL-1 . 28

6. RATIONALE AND PROPOSED AEGL-2 . 29

6.1 Summary of Human Data Relevant to AEGL-2 29

6.2 Summary of Animal Data Relevant to AEGL-2 . 30

6.3 Derivation of AEGL-2 . 30

7. RATIONALE AND PROPOSED AEGL-3 . 31

7.1 Summary of Human Data Relevant to AEGL-3 31

7.2 Summary of Animal Data Relevant to AEGL-3 31

7.3 Derivation of AEGL-3 31

8. SUMMARY OF PROPOSED AEGLS 33

8.1 AEGL Values and Toxicity Endpoints . 33

8.2 Comparison with Other Standards and Criteria . 33

8.3 Confidence in the Proposed AEGLs . 33

8.4 Data Deficiencies . 33

9. REFERENCES CITED 34

APPENDIX A (Derivation of AEGL Values) 44

APPENDIX B (Determination of Temporal Scaling Factor [n] for AEGL Derivations . 51

APPENDIX C (AEGL-1 Derivations using Alternate Approaches) . 54

APPENDIX D (Carcinogenicity Assessment for Sulfur Mustard [Agent HD]) . 57