EVALUATION OF AIRBORNE EXPOSURE LIMITS FOR SULFUR

4,19

MB

MUSTARD: OCCUPATIONAL AND GENERAL POPULATION EXPOSURE

126

stron

CRITERIA

3829

ID

United States Army Center for Health Promotion & Preventive Medicine

2001

rok

CONTENTS

PREFACE. i

ACKNOWLEDGMENTS ii

LIST OF TABLES. vi

EXECUTIVE SUMMARY.viii

1. PURPOSE. 1

2. BACKGROUND 1

2.1 Introduction . 1

2.2 Chemical and Physical Properties 2

2.3 Biological Properties 3

2.3.1 Mechanism of Action . 3

2.3.2 Absorption, Distribution and Metabolism . 4

2.3.3 Local vs. Systemic Effects 5

2.3.4 Acute Toxicity 6

2.3.4.1 Effects on the Eyes 6

2.3.4.2 Effects on the Respiratory Tract. 9

2.3.4.3 Effects on the Skin 10

2.3.4.4 Sensitization12

2.3.4.5 Systemic Effects13

2.3.5 Subchronic Toxicity13

2.3.6 Chronic Toxicity.14

2.3.6.1 Human Data .14

2.3.6.2 Animal Studies15

2.3.7 Chronic and Delayed/Recurrent Effects from Acute Exposures19

2.3.8 Developmental and Reproductive Effects 22

2.3.8.1 Human Data .22

2.3.8.2 Animal Studies22

2.3.9 Genotoxicity .25

2.3.10 Carcinogenicity26

2.3.10.1 Human Data .27

2.3.10.2 Animal Studies31

2.3.11 Summary of Biological and Toxicological Properties 35

2.4 Existing Toxicity Values for Sulfur Mustard .37

2.4.1 Oral Reference Dose.37

2.4.2 Inhalation Unit Risk38

2.5 Existing Air Exposure Limits for Sulfur Mustard42

2.5.1 General Population Exposure Limits (GPL)42

2.5.2 Worker Population Exposure Limits (WPL) .43

3. FINDINGS AND DISCUSSION .43

3.1 Exposure Data .43

3.1.1 Human Data.43

3.1.1.1 Epidemiological Studies .43

3.1.1.2 Laboratory Studies44

3.1.2 Animal Exposure Data .49

3.2 Developing Exposure Limits: A Traditional Approach.49

3.2.1 Methods for Deriving Exposure Limits for Noncancer Endpoints 49

3.2.2 Exposure Limits for Cancer Endpoints 53

3.3 Carcinogenicity Assessment for Sulfur Mustard 55

3.3.1 Hazard Characterization .55

3.3.2 Mode of Action of Sulfur Mustard.55

3.3.3 Dose-Response Analysis 56

3.4 Selecting the Critical Effect for a Noncancer Endpoint.60

3.4.1 Human Data.60

3.4.2 Animal Data.64

3.5 Airborne Exposure Levels (AELs) for Sulfur Mustard64

3.5.1 AELs for Chronic Exposures .64

3.5.1.1 General Population AELs for Chronic Exposures (GPL)64

3.5.1.2 Worker AELs for Chronic Exposures (WPL)71

3.5.2 AELs for Short-term Exposures for Workers 76

3.5.2.1 Short-term Exposure Limit (STEL) .76

3.5.2.2 Immediately Dangerous to Life or Health (IDLH) Exposure Limit 81

4. DISCUSSION AND CONCLUSIONS84

4.1 AELs for Chronic Exposures .84

4.1.1 General Population AEL for Chronic Exposures (GPL) .84

4.1.1.1 Carcinogenicity Assessment.85

4.1.2 Worker AEL for Chronic Exposures (WPL) .87

4.1.2.1 Carcinogenicity Assessment.87

4.2 AELs for Short-term Exposures to Workers .88

4.2.1 STEL88

4.2.2 IDLH88

5. RECOMMENDATIONS .88

LITERATURE CITED .90

GLOSSARY.104

APPENDIX A. Logistic and Probit Analysis for Estimation of Sulfur Mustard STEL A-1