| | DRAFT TOXICOLOGICAL PROFILE FOR ARSENIC |
| | 10,5 | | MB |
| | 533 | | stron |
| | 3456 | | ID | Agency for Toxic Substances and Disease Registry |
| | 2005 | | rok |
| | CONTENTS |
| | DISCLAIMER ii |
| | 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 TABLES xix |
| | 1. PUBLIC HEALTH STATEMENT. 1 |
| | 1.1 WHAT IS ARSENIC?.. 1 |
| | 1.2 WHAT HAPPENS TO ARSENIC WHEN IT ENTERS THE ENVIRONMENT?..3 |
| | 1.3 HOW MIGHT I BE EXPOSED TO ARSENIC? 4 |
| | 1.4 HOW CAN ARSENIC ENTER AND LEAVE MY BODY? .. 6 |
| | 1.5 HOW CAN ARSENIC AFFECT MY HEALTH? . 6 |
| | 1.6 HOW CAN ARSENIC AFFECT CHILDREN? . 8 |
| | 1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO ARSENIC? . 10 |
| | 1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED TO |
| | ARSENIC? . 11 |
| | 1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO PROTECT |
| | HUMAN HEALTH?.. 12 |
| | 1.10 WHERE CAN I GET MORE INFORMATION? 13 |
| | 2. RELEVANCE TO PUBLIC HEALTH . 15 |
| | 2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO ARSENIC IN THE UNITED STATES |
| | 15 |
| | 2.2 SUMMARY OF HEALTH EFFECTS.. 16 |
| | 2.3 MINIMAL RISK LEVELS . 24 |
| | 3. HEALTH EFFECTS 29 |
| | 3.1 INTRODUCTION 29 |
| | 3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE . 29 |
| | 3.2.1 Inhalation Exposure .. 32 |
| | 3.2.1.1 Death . 43 |
| | 3.2.1.2 Systemic Effects .. 43 |
| | 3.2.1.3 Immunological and Lymphoreticular Effects 51 |
| | 3.2.1.4 Neurological Effects .. 51 |
| | 3.2.1.5 Reproductive Effects 53 |
| | 3.2.1.6 Developmental Effects . 53 |
| | 3.2.1.7 Cancer.. 55 |
| | 3.2.2 Oral Exposure.. 60 |
| | 3.2.2.1 Death . 60 |
| | 3.2.2.2 Systemic Effects 128 |
| | 3.2.2.3 Immunological and Lymphoreticular Effects . 141 |
| | 3.2.2.4 Neurological Effects 141 |
| | 3.2.2.5 Reproductive Effects .. 143 |
| | 3.2.2.6 Developmental Effects .. 144 |
| | 3.2.2.7 Cancer. 147 |
| | 3.2.3 Dermal Exposure.. 153 |
| | 3.2.3.1 Death .. 153 |
| | 3.2.3.2 Systemic Effects 155 |
| | 3.2.3.3 Immunological and Lymphoreticular Effects . 156 |
| | 3.2.3.4 Neurological Effects 157 |
| | 3.2.3.5 Reproductive Effects .. 157 |
| | 3.2.3.6 Developmental Effects .. 157 |
| | 3.2.3.7 Cancer. 157 |
| | 3.3 GENOTOXICITY . 157 |
| | 3.4 TOXICOKINETICS. 169 |
| | 3.4.1 Absorption.. 170 |
| | 3.4.1.1 Inhalation Exposure. 170 |
| | 3.4.1.2 Oral Exposure . 170 |
| | 3.4.1.3 Dermal Exposure .. 173 |
| | 3.4.2 Distribution . 173 |
| | 3.4.2.1 Inhalation Exposure. 173 |
| | 3.4.2.2 Oral Exposure . 174 |
| | 3.4.2.3 Dermal Exposure .. 175 |
| | 3.4.2.4 Other Routes of Exposure 175 |
| | 3.4.3 Metabolism. 176 |
| | 3.4.4 Elimination and Excretion 180 |
| | 3.4.4.1 Inhalation Exposure. 180 |
| | 3.4.4.2 Oral Exposure . 181 |
| | 3.4.4.3 Dermal Exposure .. 181 |
| | 3.4.4.4 Other Routes of Exposure 181 |
| | 3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models .. 182 |
| | 3.4.5.1 Summary of PBPK Models 183 |
| | 3.4.5.2 Arsenic PBPK Model Comparison 185 |
| | 3.4.5.3 Discussion of Models 185 |
| | 3.5 MECHANISMS OF ACTION 197 |
| | 3.5.1 Pharmacokinetic Mechanisms 197 |
| | 3.5.2 Mechanisms of Toxicity 201 |
| | 3.5.3 Animal-to-Human Extrapolations 203 |
| | 3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS 204 |
| | 3.7 CHILDREN'S SUSCEPTIBILITY204 |
| | 3.8 BIOMARKERS OF EXPOSURE AND EFFECT 209 |
| | 3.8.1 Biomarkers Used to Identify or Quantify Exposure to Arsenic 210 |
| | 3.8.2 Biomarkers Used to Characterize Effects Caused by Arsenic .. 213 |
| | 3.9 INTERACTIONS WITH OTHER CHEMICALS 214 |
| | 3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 216 |
| | 3.11 METHODS FOR REDUCING TOXIC EFFECTS.. 217 |
| | 3.11.1 Reducing Peak Absorption Following Exposure 217 |
| | 3.11.2 Reducing Body Burden 218 |
| | 3.11.3 Interfering with the Mechanism of Action for Toxic Effects .. 219 |
| | 3.12 ADEQUACY OF THE DATABASE.. 220 |
| | 3.12.1 Existing Information on Health Effects of Arsenic .. 220 |
| | 3.12.2 Identification of Data Needs . 223 |
| | 3.12.3 Ongoing Studies.. 233 |
| | 4. CHEMICAL AND PHYSICAL INFORMATION 237 |
| | 4.1 CHEMICAL IDENTITY 237 |
| | 4.2 PHYSICAL AND CHEMICAL PROPERTIES. 237 |
| | 5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL . 249 |
| | 5.1 PRODUCTION .. 249 |
| | 5.2 IMPORT/EXPORT .. 254 |
| | 5.3 USE.. 254 |
| | 5.4 DISPOSAL 257 |
| | 6. POTENTIAL FOR HUMAN EXPOSURE .. 259 |
| | 6.1 OVERVIEW 259 |
| | 6.2 RELEASES TO THE ENVIRONMENT .. 262 |
| | 6.2.1 Air .. 262 |
| | 6.2.2 Water . 268 |
| | 6.2.3 Soil . 269 |
| | 6.3 ENVIRONMENTAL FATE. 270 |
| | 6.3.1 Transport and Partitioning 270 |
| | 6.3.2 Transformation and Degradation . 276 |
| | 6.3.2.1 Air 276 |
| | 6.3.2.2 Water .. 276 |
| | 6.3.2.3 Sediment and Soil. 278 |
| | 6.3.2.4 Other Media. 279 |
| | 6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT . 280 |
| | 6.4.1 Air .. 280 |
| | 6.4.2 Water . 282 |
| | 6.4.3 Sediment and Soil 289 |
| | 6.4.4 Other Environmental Media 293 |
| | 6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE . 301 |
| | 6.6 EXPOSURES OF CHILDREN .. 314 |
| | 6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES . 319 |
| | 6.8 ADEQUACY OF THE DATABASE.. 321 |
| | 6.8.1 Identification of Data Needs .. 321 |
| | 6.8.2 Ongoing Studies 324 |
| | 7. ANALYTICAL METHODS 329 |
| | 7.1 BIOLOGICAL MATERIALS . 329 |
| | 7.2 ENVIRONMENTAL SAMPLES.. 333 |
| | 7.3 ADEQUACY OF THE DATABASE.. 334 |
| | 7.3.1 Identification of Data Needs .. 338 |
| | 7.3.2 Ongoing Studies 339 |
| | 8. REGULATIONS AND ADVISORIES .. 341 |
| | 9. REFERENCES .. 347 |
| | 10. GLOSSARY . 483 |
| | 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 |