NERVE AGENT VX - PROPOSED TEMPORARY ACUTE EXPOSURE

0,27

MB

GUIDELINE LEVELS (AEGLs)

71

stron

4649

ID

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

2001

rok

TABLE OF CONTENTS

PREFACE . i

LIST OF TABLES . iv

EXECUTIVE SUMMARY . v

1. INTRODUCTION . 1

2. HUMAN TOXICITY DATA . 4

2.1. Acute Lethality 4

2.2. Nonlethal Toxicity . 4

2.2.1. Acute Exposure Studies 5

2.2.2. Epidemiologic Studies 9

2.3. Neurotoxicity 9

2.4. Developmental/Reproductive Toxicity . 9

2.5. Genotoxicity . 9

2.6. Carcinogenicity . 10

2.7. Summary . 10

3. ANIMAL TOXICITY DATA 11

3.1. Acute Lethality 11

3.2. Nonlethal Toxicity . 12

3.2.1. Rats 12

3.2.2. Mice . 13

3.2.3. Guinea Pigs 13

3.2.4. Rabbits . 13

3.3. Neurotoxicity 14

3.4. Developmental/Reproductive Toxicity . 15

3.5. Genotoxicity . 16

3.6. Carcinogenicity . 17

3.7. Summary . 17

4. SPECIAL CONSIDERATIONS 17

4.1. Metabolism and Disposition 17

4.2. Mechanism of Toxicity 18

4.3. Relative Potency . 18

4.4. Structure-Activity Relationships 22

4.5. Other Relevant Information . 23

4.5.1. Breathing Rates and Toxicity 23

4.5.2. Delayed Neuropathy . 23

4.5.3. Intra- and Inter-Species Variability in Esterase Activity and Response to Nerve Agents 24

4.5.4. Unique Physicochemical Properties . 26

4.5.5. Concurrent Exposure Issues . 26

4.5.6. Critical Effect Endpoint 28

4.5.7. Casualty Management and Care 28

5. DATA ANALYSIS AND PROPOSED AEGL-1 . 29

5.1. Summary of Human Data Relevant to AEGL-1 . 29

5.2. Summary of Animal Data Relevant to AEGL-1 . 30

5.3. Derivation of AEGL-1 30

6. DATA ANALYSIS AND PROPOSED AEGL-2 . 31

6.1. Summary of Human Data Relevant to AEGL-2 . 31

6.2. Summary of Animal Data Relevant to AEGL-2 . 31

6.3. Derivation of AEGL-2 31

7. DATA ANALYSIS AND PROPOSED AEGL-3 . 32

7.1. Summary of Human Data Relevant to AEGL-3 . 32

7.2. Summary of Animal Data Relevant to AEGL-3 . 33

7.3. Derivation of AEGL-3 33

8. SUMMARY OF PROPOSED AEGLS 34

8.1. AEGL Values and Toxicity Endpoints . 34

8.2. Comparison with Other Standards and Criteria 35

8.3. Data Adequacy and Research Needs 36

9. REFERENCES 38

APPENDIX A: Derivation of AEGL Values . A-1

APPENDIX B: Summary Tables .. B-1