| | TOXICOLOGICAL PROFILE FOR HEXACHLOROBENZENE |
| | 2,46 | | MB |
| | 403 | | stron |
| | 5557 | | ID | Agency for Toxic Substances and Disease Registry |
| | 2002 | | rok |
| | CONTENTS |
| | FOREWORD . v |
| | QUICK REFERENCE FOR HEALTH CARE PROVIDERS . vii |
| | CONTRIBUTORS . ix |
| | PEER REVIEW . xi |
| | LIST OF FIGURES xvii |
| | LIST OF TABLES xix |
| | 1. PUBLIC HEALTH STATEMENT 1 |
| | 1.1 WHAT IS HEXACHLOROBENZENE? 1 |
| | 1.2 WHAT HAPPENS TO HEXACHLOROBENZENE WHEN IT ENTERS THE ENVIRONMENT? . 2 |
| | 1.3 HOW MIGHT I BE EXPOSED TO HEXACHLOROBENZENE? 2 |
| | 1.4 HOW CAN HEXACHLOROBENZENE ENTER AND LEAVE MY BODY? 3 |
| | 1.5 HOW CAN HEXACHLOROBENZENE AFFECT MY HEALTH? . 4 |
| | 1.6 HOW CAN HEXACHLOROBENZENE AFFECT CHILDREN? 5 |
| | 1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO HEXACHLOROBENZENE? . 7 |
| | 1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED TO |
| | HEXACHLOROBENZENE? . 8 |
| | 1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO PROTECT |
| | HUMAN HEALTH? 9 |
| | 1.10 WHERE CAN I GET MORE INFORMATION? 10 |
| | 2. RELEVANCE TO PUBLIC HEALTH . 11 |
| | 2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO HEXACHLOROBENZENE IN THE |
| | UNITED STATES . 11 |
| | 2.2 SUMMARY OF HEALTH EFFECTS . 12 |
| | 2.3 MINIMAL RISK LEVELS (MRLs) 16 |
| | 3. HEALTH EFFECTS 23 |
| | 3.1 INTRODUCTION 23 |
| | 3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE . 23 |
| | 3.2.1 Inhalation Exposure 25 |
| | 3.2.1.1 Death . 25 |
| | 3.2.1.2 Systemic Effects 25 |
| | 3.2.1.3 Immunological and Lymphoreticular Effects 33 |
| | 3.2.1.4 Neurological Effects . 34 |
| | 3.2.1.5 Reproductive Effects . 34 |
| | 3.2.1.6 Developmental Effects . 35 |
| | 3.2.1.7 Cancer 35 |
| | 3.2.2 Oral Exposure 36 |
| | 3.2.2.1 Death . 36 |
| | 3.2.2.2 Systemic Effects 38 |
| | 3.2.2.3 Immunological and Lymphoreticular Effects 95 |
| | 3.2.2.4 Neurological Effects . 99 |
| | 3.2.2.5 Reproductive Effects 102 |
| | 3.2.2.6 Developmental Effects 107 |
| | 3.2.2.7 Cancer . 111 |
| | 3.2.3 Dermal Exposure . 115 |
| | 3.2.3.1 Death 115 |
| | 3.2.3.2 Systemic Effects . 115 |
| | 3.2.3.3 Immunological and Lymphoreticular Effects . 115 |
| | 3.2.3.4 Neurological Effects 115 |
| | 3.2.3.5 Reproductive Effects 115 |
| | 3.2.3.6 Developmental Effects 115 |
| | 3.2.3.7 Cancer . 116 |
| | 3.3 GENOTOXICITY . 116 |
| | 3.4 TOXICOKINETICS 118 |
| | 3.4.1 Absorption 123 |
| | 3.4.1.1 Inhalation Exposure . 123 |
| | 3.4.1.2 Oral Exposure . 125 |
| | 3.4.1.3 Dermal Exposure . 128 |
| | 3.4.2 Distribution . 129 |
| | 3.4.2.1 Inhalation Exposure . 129 |
| | 3.4.2.2 Oral Exposure . 130 |
| | 3.4.2.3 Dermal Exposure . 135 |
| | 3.4.3 Metabolism 135 |
| | 3.4.3.1 Inhalation Exposure . 135 |
| | 3.4.3.2 Oral Exposure . 135 |
| | 3.4.3.3 Dermal Exposure . 140 |
| | 3.4.4 Elimination and Excretion 140 |
| | 3.4.4.1 Inhalation Exposure . 140 |
| | 3.4.4.2 Oral Exposure . 141 |
| | 3.4.4.3 Dermal Exposure . 143 |
| | 3.4.4.4 Other Routes of Exposure 143 |
| | 3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models . 143 |
| | 3.4.5.1 Summary of PBPK Models . 145 |
| | 3.4.5.2 Hexachlorobenzene PBPK Model Comparison . 145 |
| | 3.4.5.3 Discussion of Models . 147 |
| | 3.5 MECHANISMS OF ACTION 149 |
| | 3.5.1 Pharmacokinetic Mechanisms . 149 |
| | 3.5.2 Mechanisms of Toxicity 152 |
| | 3.5.3 Animal-to-Human Extrapolations 155 |
| | 3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS 155 |
| | 3.7 CHILDREN’S SUSCEPTIBILITY 157 |
| | 3.8 BIOMARKERS OF EXPOSURE AND EFFECT . 160 |
| | 3.8.1 Biomarkers Used to Identify or Quantify Exposure to Hexachlorobenzene 161 |
| | 3.8.2 Biomarkers Used to Characterize Effects Caused by Hexachlorobenzene . 162 |
| | 3.9 INTERACTIONS WITH OTHER CHEMICALS . 163 |
| | 3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 167 |
| | 3.11 METHODS FOR REDUCING TOXIC EFFECTS 168 |
| | 3.11.1 Reducing Peak Absorption Following Exposure . 168 |
| | 3.11.2 Reducing Body Burden 169 |
| | 3.11.3 Interfering with the Mechanism of Action for Toxic Effects 170 |
| | 3.12 ADEQUACY OF THE DATABASE . 171 |
| | 3.12.1 Existing Information on Health Effects of Hexachlorobenzene . 172 |
| | 3.12.2 Identification of Data Needs 172 |
| | 3.12.3 Ongoing Studies 186 |
| | 4. CHEMICAL AND PHYSICAL INFORMATION 187 |
| | 4.1 CHEMICAL IDENTITY 187 |
| | 4.2 PHYSICAL AND CHEMICAL PROPERTIES . 187 |
| | 5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 191 |
| | 5.1 PRODUCTION . 191 |
| | 5.2 IMPORT/EXPORT 192 |
| | 5.3 USE . 194 |
| | 5.4 DISPOSAL . 194 |
| | 6. POTENTIAL FOR HUMAN EXPOSURE . 197 |
| | 6.1 OVERVIEW 197 |
| | 6.2 RELEASES TO THE ENVIRONMENT 200 |
| | 6.2.1 Air 201 |
| | 6.2.2 Water 204 |
| | 6.2.3 Soil 206 |
| | 6.3 ENVIRONMENTAL FATE 208 |
| | 6.3.1 Transport and Partitioning 208 |
| | 6.3.2 Transformation and Degradation . 213 |
| | 6.3.2.1 Air 213 |
| | 6.3.2.2 Water 214 |
| | 6.3.2.3 Sediment and Soil 215 |
| | 6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT . 216 |
| | 6.4.1 Air 217 |
| | 6.4.2 Water 219 |
| | 6.4.3 Sediment and Soil 220 |
| | 6.4.4 Other Environmental Media . 222 |
| | 6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 232 |
| | 6.6 EXPOSURES OF CHILDREN . 236 |
| | 6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 240 |
| | 6.8 ADEQUACY OF THE DATABASE . 242 |
| | 6.8.1 Identification of Data Needs 243 |
| | 6.8.2 Ongoing Studies 248 |
| | 7. ANALYTICAL METHODS . 250 |
| | 7.1 BIOLOGICAL MATERIALS 250 |
| | 7.2 ENVIRONMENTAL SAMPLES 254 |
| | 7.3 ADEQUACY OF THE DATABASE . 261 |
| | 7.3.1 Identification of Data Needs 262 |
| | 7.3.2 Ongoing Studies 264 |
| | 8. REGULATIONS AND ADVISORIES 266 |
| | 9. REFERENCES . 274 |
| | 10. GLOSSARY 346 |
| | APPENDICES |
| | A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS . A-1 |
| | B. USER’S GUIDE . B-1 |
| | C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS . C-1 |
| | D. INDEX . . D-1 |