| | TOXICOLOGICAL PROFILE FOR AMERICIUM |
| | 2,14 | | MB |
| | 333 | | stron |
| | 5555 | | 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 AMERICIUM?. 2 |
| | 1.2 WHAT HAPPENS TO AMERICIUM WHEN IT ENTERS THE ENVIRONMENT? . 3 |
| | 1.3 HOW MIGHT I BE EXPOSED TO AMERICIUM? 4 |
| | 1.4 HOW CAN AMERICIUM ENTER AND LEAVE MY BODY?. 5 |
| | 1.5 HOW CAN AMERICIUM AFFECT MY HEALTH? 5 |
| | 1.6 HOW CAN AMERICIUM AFFECT CHILDREN? . 6 |
| | 1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO AMERICIUM?. 7 |
| | 1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED TO |
| | AMERICIUM? 8 |
| | 1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO PROTECT |
| | HUMAN HEALTH? 8 |
| | 1.10 WHERE CAN I GET MORE INFORMATION? . 10 |
| | 2. RELEVANCE TO PUBLIC HEALTH .11 |
| | 2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO AMERICIUM IN THE UNITED |
| | STATES 11 |
| | 2.2 SUMMARY OF HEALTH EFFECTS 12 |
| | 2.3 MINIMAL RISK LEVELS (MRLs) . 14 |
| | 3. HEALTH EFFECTS. 15 |
| | 3.1 INTRODUCTION 15 |
| | 3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE 17 |
| | 3.2.1 Inhalation Exposure 19 |
| | 3.2.1.1 Death 19 |
| | 3.2.1.2 Systemic Effects . 19 |
| | 3.2.1.3 Immunological and Lymphoreticular Effects. 23 |
| | 3.2.1.4 Neurological Effects. 24 |
| | 3.2.1.5 Reproductive Effects 24 |
| | 3.2.1.6 Developmental Effects . 24 |
| | 3.2.1.7 Cancer 24 |
| | 3.2.2 Oral Exposure. 24 |
| | 3.2.2.1 Death 25 |
| | 3.2.2.2 Systemic Effects . 25 |
| | 3.2.2.3 Immunological and Lymphoreticular Effects. 25 |
| | 3.2.2.4 Neurological Effects. 25 |
| | 3.2.2.5 Reproductive Effects 25 |
| | 3.2.2.6 Developmental Effects . 25 |
| | 3.2.2.7 Cancer 25 |
| | 3.2.3 Dermal Exposure. 25 |
| | 3.2.3.1 Death 25 |
| | 3.2.3.2 Systemic Effects . 25 |
| | 3.2.3.3 Immunological and Lymphoreticular Effects. 26 |
| | 3.2.3.4 Neurological Effects. 27 |
| | 3.2.3.5 Reproductive Effects 27 |
| | 3.2.3.6 Developmental Effects . 27 |
| | 3.2.3.7 Cancer 27 |
| | 3.2.4 Other Routes of Exposure . 27 |
| | 3.2.4.1 Death 27 |
| | 3.2.4.2 Systemic Effects . 27 |
| | 3.2.4.3 Immunological and Lymphoreticular Effects. 28 |
| | 3.2.4.4 Neurological Effects. 29 |
| | 3.2.4.5 Reproductive Effects 29 |
| | 3.2.4.6 Developmental Effects . 29 |
| | 3.2.4.7 Cancer 30 |
| | 3.3 GENOTOXICITY . 31 |
| | 3.4 TOXICOKINETICS. 32 |
| | 3.4.1 Absorption 32 |
| | 3.4.1.1 Inhalation Exposure 32 |
| | 3.4.1.2 Oral Exposure. 38 |
| | 3.4.1.3 Dermal Exposure 43 |
| | 3.4.1.4 Other Routes of Exposure 44 |
| | 3.4.2 Distribution . 44 |
| | 3.4.2.1 Inhalation Exposure 44 |
| | 3.4.2.2 Oral Exposure. 49 |
| | 3.4.2.3 Dermal Exposure 49 |
| | 3.4.2.4 Other Routes of Exposure 50 |
| | 3.4.3 Metabolism. 51 |
| | 3.4.4 Elimination and Excretion. 51 |
| | 3.4.4.1 Inhalation Exposure 51 |
| | 3.4.4.2 Oral Exposure. 53 |
| | 3.4.4.3 Dermal Exposure 54 |
| | 3.4.4.4 Other Routes of Exposure 54 |
| | 3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models . 55 |
| | 3.5 MECHANISMS OF ACTION 79 |
| | 3.5.1 Pharmacokinetic Mechanisms. 79 |
| | 3.5.2 Mechanisms of Toxicity 83 |
| | 3.5.3 Animal-to-Human Extrapolations .83 |
| | 3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS 84 |
| | 3.7 CHILDREN’S SUSCEPTIBILITY. 85 |
| | 3.8 BIOMARKERS OF EXPOSURE AND EFFECT 88 |
| | 3.8.1 Biomarkers Used to Identify or Quantify Exposure to Americium 89 |
| | 3.8.2 Biomarkers Used to Characterize Effects Caused by Americium. 90 |
| | 3.9 INTERACTIONS WITH OTHER CHEMICALS 90 |
| | 3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE. 91 |
| | 3.11 METHODS FOR REDUCING TOXIC EFFECTS. 91 |
| | 3.11.1 Reducing Peak Absorption Following Exposure 92 |
| | 3.11.2 Reducing Body Burden. 92 |
| | 3.11.3 Interfering with the Mechanism of Action for Toxic Effects . 93 |
| | 3.12 ADEQUACY OF THE DATABASE 93 |
| | 3.12.1 Existing Information on Health Effects of Americium. 93 |
| | 3.12.2 Identification of Data Needs . 95 |
| | 3.12.3 Ongoing Studies 101 |
| | 4. CHEMICAL, PHYSICAL, and RADIOLOGICAL INFORMATION . 103 |
| | 4.1 CHEMICAL IDENTITY. 103 |
| | 4.2 PHYSICAL, CHEMICAL, AND RADIOLOGICAL PROPERTIES. 103 |
| | 5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 113 |
| | 5.1 PRODUCTION . 113 |
| | 5.2 IMPORT/EXPORT . 116 |
| | 5.3 USE. 116 |
| | 5.4 DISPOSAL. 117 |
| | 6. POTENTIAL FOR HUMAN EXPOSURE . 121 |
| | 6.1 OVERVIEW. 121 |
| | 6.2 RELEASES TO THE ENVIRONMENT 125 |
| | 6.2.1 Air 126 |
| | 6.2.2 Water 128 |
| | 6.2.3 Soil . 129 |
| | 6.3 ENVIRONMENTAL FATE 130 |
| | 6.3.1 Transport and Partitioning. 130 |
| | 6.3.2 Transformation and Degradation 148 |
| | 6.3.2.1 Air 148 |
| | 6.3.2.2 Water 148 |
| | 6.3.2.3 Sediment and Soil. 148 |
| | 6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT. 149 |
| | 6.4.1 Air 149 |
| | 6.4.2 Water 151 |
| | 6.4.3 Sediment and Soil . 154 |
| | 6.4.4 Other Environmental Media 158 |
| | 6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE . 170 |
| | 6.6 EXPOSURES OF CHILDREN. 176 |
| | 6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES . 177 |
| | 6.8 ADEQUACY OF THE DATABASE 178 |
| | 6.8.1 Identification of Data Needs . 178 |
| | 6.8.2 Ongoing Studies 182 |
| | 7. ANALYTICAL METHODS . 183 |
| | 7.1 BIOLOGICAL MATERIALS. 183 |
| | 7.1.1 Whole or Partial Body Measurements 183 |
| | 7.1.2 Assay of Excreta . 188 |
| | 7.2 ENVIRONMENTAL SAMPLES 190 |
| | 7.2.1 Field Measurements of Americium. 190 |
| | 7.2.2 Laboratory Analysis of Environmental Samples. 191 |
| | 7.3 ADEQUACY OF THE DATABASE 198 |
| | 7.3.1 Identification of Data Needs . 198 |
| | 7.3.2 Ongoing Studies 199 |
| | 8. REGULATIONS AND ADVISORIES .201 |
| | 9. REFERENCES . 209 |
| | 10. GLOSSARY . 259 |
| | APPENDIX A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS.A-1 |