| | TOXICOLOGICAL PROFILE FOR SULFUR MUSTARD |
| | 3,27 | | MB |
| | 217 | | stron |
| | 3460 | | ID | Agency for Toxic Substances and Disease Registry |
| | 2003 | | rok |
| | CONTENTS |
| | DISCLAIMERii |
| | UPDATE STATEMENT.iii |
| | FOREWORD..v |
| | QUICK REFERENCE FOR HEALTH CARE PROVIDERS..vii |
| | CONTRIBUTORS..ix |
| | PEER REVIEW xi |
| | CONTENTS.xiii |
| | LIST OF FIGURES xvii |
| | LIST OF TABLESxix |
| | 1. PUBLIC HEALTH STATEMENT.1 |
| | 1.1 WHAT IS SULFUR MUSTARD?.1 |
| | 1.2 WHAT HAPPENS TO SULFUR MUSTARD WHEN IT ENTERS THE ENVIRONMENT?2 |
| | 1.3 HOW MIGHT I BE EXPOSED TO SULFUR MUSTARD? ..3 |
| | 1.4 HOW CAN SULFUR MUSTARD ENTER AND LEAVE MY BODY? .3 |
| | 1.5 HOW CAN SULFUR MUSTARD AFFECT MY HEALTH? 4 |
| | 1.6 HOW CAN SULFUR MUSTARD AFFECT CHILDREN?.5 |
| | 1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO SULFUR MUSTARD?.5 |
| | 1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED TO |
| | SULFUR MUSTARD? 6 |
| | 1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO PROTECT |
| | HUMAN HEALTH?.6 |
| | 1.10 WHERE CAN I GET MORE INFORMATION? ..7 |
| | 2. RELEVANCE TO PUBLIC HEALTH 9 |
| | 2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO SULFUR MUSTARD IN THE |
| | UNITED STATES..9 |
| | 2.2 SUMMARY OF HEALTH EFFECTS..11 |
| | 2.3 MINIMAL RISK LEVELS .15 |
| | 3. HEALTH EFFECTS..21 |
| | 3.1 INTRODUCTION..21 |
| | 3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE .22 |
| | 3.2.1 Inhalation Exposure ..24 |
| | 3.2.1.1 Death .24 |
| | 3.2.1.2 Systemic Effects ..26 |
| | 3.2.1.3 Immunological and Lymphoreticular Effects41 |
| | 3.2.1.4 Neurological Effects..41 |
| | 3.2.1.5 Reproductive Effects .42 |
| | 3.2.1.6 Developmental Effects .43 |
| | 3.2.1.7 Cancer..43 |
| | 3.2.2 Oral Exposure..47 |
| | 3.2.2.1 Death .47 |
| | 3.2.2.2 Systemic Effects ..48 |
| | 3.2.2.3 Immunological and Lymphoreticular Effects57 |
| | 3.2.2.3 Neurological Effects..57 |
| | 3.2.2.4 Reproductive Effects .58 |
| | 3.2.2.5 Developmental Effects .59 |
| | 3.2.2.7 Cancer..60 |
| | 3.2.3 Dermal Exposure.60 |
| | 3.2.3.1 Death .60 |
| | 3.2.3.2 Systemic Effects ..60 |
| | 3.2.3.3 Immunological and Lymphoreticular Effects64 |
| | 3.2.3.4 Neurological Effects..65 |
| | 3.2.3.5 Reproductive Effects .65 |
| | 3.2.3.6 Developmental Effects .65 |
| | 3.2.3.7 Cancer..65 |
| | 3.2.4 Other Routes of Exposure ..66 |
| | 3.3 GENOTOXICITY 67 |
| | 3.4 TOXICOKINETICS..70 |
| | 3.4.1 Absorption.70 |
| | 3.4.1.1 Inhalation Exposure70 |
| | 3.4.1.2 Oral Exposure71 |
| | 3.4.1.3 Dermal Exposure .71 |
| | 3.4.2 Distribution 72 |
| | 3.4.2.1 Inhalation Exposure72 |
| | 3.4.2.2 Oral Exposure72 |
| | 3.4.2.3 Dermal Exposure .72 |
| | 3.4.2.4 Other Routes of Exposure ..73 |
| | 3.4.3 Metabolism74 |
| | 3.4.3.1 Inhalation Exposure75 |
| | 3.4.3.2 Oral Exposure75 |
| | 3.4.3.3 Dermal Exposure .75 |
| | 3.4.3.4 Other Routes of Exposure ..76 |
| | 3.4.4 Elimination and Excretion..77 |
| | 3.4.4.1 Inhalation Exposure77 |
| | 3.4.4.2 Oral Exposure77 |
| | 3.4.4.3 Dermal Exposure .78 |
| | 3.4.4.4 Other Routes of Exposure ..78 |
| | 3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models .79 |
| | 3.5 MECHANISMS OF ACTION ..82 |
| | 3.5.1 Pharmacokinetic Mechanisms..82 |
| | 3.5.2 Mechanisms of Toxicity..82 |
| | 3.5.3 Animal-to-Human Extrapolations ..89 |
| | 3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS..91 |
| | 3.7 CHILDREN’S SUSCEPTIBILITY.94 |
| | 3.8 BIOMARKERS OF EXPOSURE AND EFFECT ..96 |
| | 3.8.1 Biomarkers Used to Identify or Quantify Exposure to Sulfur mustard97 |
| | 3.8.2 Biomarkers Used to Characterize Effects Caused by Sulfur mustard..99 |
| | 3.9 INTERACTIONS WITH OTHER CHEMICALS 100 |
| | 3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE100 |
| | 3.11 METHODS FOR REDUCING TOXIC EFFECTS..100 |
| | 3.11.1 Reducing Peak Absorption Following Exposure .101 |
| | 3.11.2 Reducing Body Burden .102 |
| | 3.11.3 Interfering with the Mechanism of Action for Toxic Effects.105 |
| | 3.12 ADEQUACY OF THE DATABASE..107 |
| | 3.12.1 Existing Information on Health Effects of Sulfur Mustard .109 |
| | 3.12.2 Identification of Data Needs ..109 |
| | 3.12.3 Ongoing Studies 116 |
| | 4. CHEMICAL AND PHYSICAL INFORMATION 119 |
| | 4.1 CHEMICAL IDENTITY119 |
| | 4.2 PHYSICAL AND CHEMICAL PROPERTIES.119 |
| | 5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL.125 |
| | 5.1 PRODUCTION ..125 |
| | 5.2 IMPORT/EXPORT ..127 |
| | 5.3 USE..127 |
| | 5.4 DISPOSAL..127 |
| | 6. POTENTIAL FOR HUMAN EXPOSURE ..131 |
| | 6.1 OVERVIEW131 |
| | 6.2 RELEASES TO THE ENVIRONMENT..131 |
| | 6.2.1 Air ..133 |
| | 6.2.2 Water.133 |
| | 6.2.3 Soil .134 |
| | 6.3 ENVIRONMENTAL FATE.134 |
| | 6.3.1 Transport and Partitioning134 |
| | 6.3.2 Transformation and Degradation .137 |
| | 6.3.2.1 Air137 |
| | 6.3.2.2 Water ..137 |
| | 6.3.2.3 Sediment and Soil.139 |
| | 6.3.2.4 Other Media.140 |
| | 6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT.140 |
| | 6.4.1 Air ..140 |
| | 6.4.2 Water.141 |
| | 6.4.3 Sediment and Soil 141 |
| | 6.4.4 Other Environmental Media141 |
| | 6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE .142 |
| | 6.6 EXPOSURES OF CHILDREN..142 |
| | 6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES .143 |
| | 6.8 ADEQUACY OF THE DATABASE..143 |
| | 6.8.1 Identification of Data Needs ..144 |
| | 6.8.2 Ongoing Studies 146 |
| | 7. ANALYTICAL METHODS 149 |
| | 7.1 BIOLOGICAL MATERIALS.149 |
| | 7.2 ENVIRONMENTAL SAMPLES..152 |
| | 7.3 ADEQUACY OF THE DATABASE..156 |
| | 7.3.1 Identification of Data Needs ..157 |
| | 7.3.2 Ongoing Studies 158 |
| | 8. REGULATIONS AND ADVISORIES ..159 |
| | 9. REFERENCES ..167 |
| | 10. GLOSSARY .211 |
| | APPENDIX A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS..A-1 |
| | APPENDIX B. USER'S GUIDE.. B-1 |
| | APPENDIX C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS. C-1 |
| | APPENDIX D. ACUTE EXPOSURE GUIDELINE LEVELS (AEGLS) FOR SULFUR MUSTARDD-1 |