| | TOXICOLOGICAL PROFILE FOR COBALT |
| | 3,42 | | MB |
| | 486 | | stron |
| | 5558 | | ID | Agency for Toxic Substances and Disease Registry |
| | 2004 | | rok |
| | CONTENTS |
| | DISCLAIMER.ii |
| | UPDATE STATEMENTiii |
| | FOREWORD. v |
| | QUICK REFERENCE FOR HEALTH CARE PROVIDERSvii |
| | CONTRIBUTORSxi |
| | PEER REVIEW xiii |
| | CONTENTS. xv |
| | LIST OF FIGURES xix |
| | LIST OF TABLESxxi |
| | 1. PUBLIC HEALTH STATEMENT 1 |
| | 1.1 WHAT IS COBALT? 2 |
| | 1.2 WHAT HAPPENS TO COBALT WHEN IT ENTERS THE ENVIRONMENT?. 4 |
| | 1.3 HOW MIGHT I BE EXPOSED TO COBALT? . 6 |
| | 1.4 HOW CAN COBALT ENTER AND LEAVE MY BODY?. 8 |
| | 1.5 HOW CAN COBALT AFFECT MY HEALTH? 8 |
| | 1.6 HOW CAN COBALT AFFECT CHILDREN?. 12 |
| | 1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO COBALT 12 |
| | 1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED TO |
| | COBALT?. 13 |
| | 1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO PROTECT |
| | HUMAN HEALTH?. 14 |
| | 1.10 WHERE CAN I GET MORE INFORMATION? . 15 |
| | 2. RELEVANCE TO PUBLIC HEALTH .17 |
| | 2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO COBALT IN THE UNITED STATES . |
| | 17 |
| | 2.2 SUMMARY OF HEALTH EFFECTS 18 |
| | 2.3 MINIMAL RISK LEVELS (MRLs)24 |
| | 3. HEALTH EFFECTS. 27 |
| | 3.1 INTRODUCTION 27 |
| | 3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE 27 |
| | 3.2.1 Inhalation Exposure 29 |
| | 3.2.1.1 Death 29 |
| | 3.2.1.2 Systemic Effects . 30 |
| | 3.2.1.3 Immunological and Lymphoreticular Effects. 50 |
| | 3.2.1.4 Neurological Effects. 51 |
| | 3.2.1.5 Reproductive Effects 51 |
| | 3.2.1.6 Developmental Effects . 52 |
| | 3.2.1.7 Cancer 52 |
| | 3.2.2 Oral Exposure. 54 |
| | 3.2.2.1 Death 54 |
| | 3.2.2.2 Systemic Effects . 55 |
| | 3.2.2.3 Immunological and Lymphoreticular Effects. 79 |
| | 3.2.2.4 Neurological Effects. 80 |
| | 3.2.2.5 Reproductive Effects 81 |
| | 3.2.2.6 Developmental Effects . 81 |
| | 3.2.2.7 Cancer 82 |
| | 3.2.3 Dermal Exposure. 83 |
| | 3.2.3.1 Death 83 |
| | 3.2.3.2 Systemic Effects . 83 |
| | 3.2.3.3 Immunological and Lymphoreticular Effects. 84 |
| | 3.2.3.4 Neurological Effects. 86 |
| | 3.2.3.5 Reproductive Effects 86 |
| | 3.2.3.6 Developmental Effects . 86 |
| | 3.2.3.7 Cancer 86 |
| | 3.2.4 Other Routes of Exposure . 86 |
| | 3.3 DISCUSSION OF HEALTH EFFECTS OF RADIOACTIVE COBALT BY ROUTE OF EXPOSURE |
| | 87 |
| | 3.3.1 Inhalation Exposure 87 |
| | 3.3.1.1 Death 87 |
| | 3.3.1.2 Systemic Effects . 87 |
| | 3.3.1.3 Immunological and Lymphoreticular Effects. 87 |
| | 3.3.1.4 Neurological Effects. 87 |
| | 3.3.1.5 Reproductive Effects 87 |
| | 3.3.1.6 Developmental Effects . 87 |
| | 3.3.1.7 Cancer 88 |
| | 3.3.2 Oral Exposure. 88 |
| | 3.3.2.1 Death 88 |
| | 3.3.2.2 Systemic Effects . 88 |
| | 3.3.2.3 Immunological and Lymphoreticular Effects. 88 |
| | 3.3.2.4 Neurological Effects. 88 |
| | 3.3.2.5 Reproductive Effects 88 |
| | 3.3.2.6 Developmental Effects . 88 |
| | 3.3.2.7 Cancer 88 |
| | 3.3.3 External Exposure . 88 |
| | 3.3.3.1 Death 106 |
| | 3.3.3.2 Systemic Effects . 107 |
| | 3.3.3.3 Immunological and Lymphoreticular Effects. 112 |
| | 3.3.3.4 Neurological Effects. 113 |
| | 3.3.3.5 Reproductive Effects 114 |
| | 3.3.3.6 Developmental Effects .115 |
| | 3.3.3.7 Cancer. 117 |
| | 3.3.4 Other Routes of Exposure . 117 |
| | 3.4 GENOTOXICITY . 118 |
| | 3.5 TOXICOKINETICS 122 |
| | 3.5.1 Absorption 122 |
| | 3.5.1.1 Inhalation Exposure 122 |
| | 3.5.1.2 Oral Exposure. 126 |
| | 3.5.1.3 Dermal Exposure 128 |
| | 3.5.1.4 Other Routes of Exposure 128 |
| | 3.5.2 Distribution . 128 |
| | 3.5.2.1 Inhalation Exposure 129 |
| | 3.5.2.2 Oral Exposure. 130 |
| | 3.5.2.3 Dermal Exposure 130 |
| | 3.5.2.4 Other Routes of Exposure 130 |
| | 3.5.3 Metabolism. 131 |
| | 3.5.4 Elimination and Excretion. 131 |
| | 3.5.4.1 Inhalation Exposure 131 |
| | 3.5.4.2 Oral Exposure. 134 |
| | 3.5.4.3 Dermal Exposure 135 |
| | 3.5.4.4 Other Routes of Exposure 135 |
| | 3.5.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models . 137 |
| | 3.6 MECHANISMS OF ACTION 152 |
| | 3.6.1 Pharmacokinetic Mechanisms.152 |
| | 3.6.2 Mechanisms of Toxicity 153 |
| | 3.6.3 Animal-to-Human Extrapolations .157 |
| | 3.7 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS 157 |
| | 3.8 CHILDREN’S SUSCEPTIBILITY. 158 |
| | 3.9 BIOMARKERS OF EXPOSURE AND EFFECT 162 |
| | 3.9.1 Biomarkers Used to Identify or Quantify Exposure to Cobalt 163 |
| | 3.9.2 Biomarkers Used to Characterize Effects Caused by Cobalt 166 |
| | 3.10 INTERACTIONS WITH OTHER CHEMICALS 166 |
| | 3.11 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE. 168 |
| | 3.12 METHODS FOR REDUCING TOXIC EFFECTS. 169 |
| | 3.12.1 Reducing Peak Absorption Following Exposure 169 |
| | 3.12.2 Reducing Body Burden. 170 |
| | 3.12.3 Interfering with the Mechanism of Action for Toxic Effects . 170 |
| | 3.13 ADEQUACY OF THE DATABASE 170 |
| | 3.13.1 Existing Information on Health Effects of Cobalt 171 |
| | 3.13.2 Identification of Data Needs . 171 |
| | 3.13.3 Ongoing Studies 182 |
| | 4. CHEMICAL, PHYSICAL, AND RADIOLOGICAL INFORMATION. 183 |
| | 4.1 CHEMICAL IDENTITY.183 |
| | 4.2 PHYSICAL, CHEMICAL, AND RADIOLOGICAL PROPERTIES. 183 |
| | 5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 195 |
| | 5.1 PRODUCTION. 195 |
| | 5.2 IMPORT/EXPORT 201 |
| | 5.3 USE. 202 |
| | 5.4 DISPOSAL . 203 |
| | 6. POTENTIAL FOR HUMAN EXPOSURE . 207 |
| | 6.1 OVERVIEW. 207 |
| | 6.2 RELEASES TO THE ENVIRONMENT 212 |
| | 6.2.1 Air 213 |
| | 6.2.2 Water 216 |
| | 6.2.3 Soil . 218 |
| | 6.3 ENVIRONMENTAL FATE219 |
| | 6.3.1 Transport and Partitioning. 219 |
| | 6.3.2 Transformation and Degradation 227 |
| | 6.3.2.1 Air 227 |
| | 6.3.2.2 Water 227 |
| | 6.3.2.3 Sediment and Soil. 229 |
| | 6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT. 230 |
| | 6.4.1 Air 230 |
| | 6.4.2 Water 231 |
| | 6.4.3 Sediment and Soil . 238 |
| | 6.4.4 Other Environmental Media 241 |