| | TOXICOLOGICAL PROFILE FOR FLUORIDES, HYDROGEN FLUORIDE, |
| | 2,16 | | MB | AND FLUORINE |
| | 404 | | stron |
| | 3457 | | ID | Agency for Toxic Substances and Disease Registry |
| | 2004 | | 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 ARE FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE? 1 |
| | 1.2 WHAT HAPPENS TO FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE WHEN THEY |
| | ENTER THE ENVIRONMENT?.. 3 |
| | 1.3 HOW MIGHT I BE EXPOSED TO FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE?. 4 |
| | |
| | 1.4 HOW CAN FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE ENTER AND LEAVE MY |
| | BODY? 6 |
| | 1.5 HOW CAN FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE AFFECT MY HEALTH?. 7 |
| | |
| | 1.6 HOW CAN FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE AFFECT CHILDREN? . 9 |
| | |
| | 1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO FLUORIDES, HYDROGEN |
| | FLUORIDE, AND FLUORINE?.. 10 |
| | 1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED TO |
| | FLUORIDES, HYDROGEN FLUORIDE, AND FLUORINE?. 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 FLUORIDES, HYDROGEN |
| | FLUORIDE, AND FLUORINE IN THE UNITED STATES 15 |
| | 2.2 SUMMARY OF HEALTH EFFECTS.. 17 |
| | 2.3 MINIMAL RISK LEVELS .22 |
| | 3. HEALTH EFFECTS.. 29 |
| | 3.1 INTRODUCTION.. 29 |
| | 3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE . 31 |
| | 3.2.1 Inhalation Exposure .. 32 |
| | 3.2.1.1 Death.. 33 |
| | 3.2.1.2 Systemic Effects 36 |
| | 3.2.1.3 Immunological and Lymphoreticular Effects . 69 |
| | 3.2.1.4 Neurological Effects 70 |
| | 3.2.1.5 Reproductive Effects 70 |
| | 3.2.1.6 Developmental Effects 71 |
| | 3.2.1.7 Cancer . 71 |
| | 3.2.2 Oral Exposure.. 72 |
| | 3.2.2.1 Death.. 74 |
| | 3.2.2.2 Systemic Effects 75 |
| | 3.2.2.3 Immunological and Lymphoreticular Effects .. 110 |
| | 3.2.2.4 Neurological Effects . 110 |
| | 3.2.2.5 Reproductive Effects. 111 |
| | 3.2.2.6 Developmental Effects. 114 |
| | 3.2.2.7 Cancer .. 117 |
| | 3.2.3 Dermal Exposure.. 125 |
| | 3.2.3.1 Death 126 |
| | 3.2.3.2 Systemic Effects . 127 |
| | 3.2.3.3 Immunological and Lymphoreticular Effects .. 132 |
| | 3.2.3.4 Neurological Effects . 132 |
| | 3.2.3.5 Reproductive Effects. 132 |
| | 3.2.3.6 Developmental Effects. 132 |
| | 3.2.3.7 Cancer .. 132 |
| | 3.3 GENOTOXICITY . 132 |
| | 3.4 TOXICOKINETICS. 136 |
| | 3.4.1 Absorption.. 136 |
| | 3.4.1.1 Inhalation Exposure .. 136 |
| | 3.4.1.2 Oral Exposure .. 138 |
| | 3.4.1.3 Dermal Exposure 139 |
| | 3.4.2 Distribution . 140 |
| | 3.4.2.1 Inhalation Exposure .. 140 |
| | 3.4.2.2 Oral Exposure .. 141 |
| | 3.4.2.3 Dermal Exposure 144 |
| | 3.4.2.4 Other Routes of Exposure..144 |
| | 3.4.3 Metabolism. 145 |
| | 3.4.4 Elimination and Excretion 145 |
| | 3.4.4.1 Inhalation Exposure .. 145 |
| | 3.4.4.2 Oral Exposure .. 146 |
| | 3.4.4.3 Dermal Exposure 147 |
| | 3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models .. 147 |
| | 3.5 MECHANISMS OF ACTION 151 |
| | 3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS 153 |
| | 3.7 CHILDREN’S SUSCEPTIBILITY..154 |
| | 3.8 BIOMARKERS OF EXPOSURE AND EFFECT 157 |
| | 3.8.1 Biomarkers Used to Identify or Quantify Exposure to Fluorides, Hydrogen Fluoride, and |
| | Fluorine 158 |
| | 3.8.2 Biomarkers Used to Characterize Effects Caused by Fluorides, Hydrogen Fluoride, and |
| | Fluorine 160 |
| | 3.9 INTERACTIONS WITH OTHER CHEMICALS 162 |
| | 3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE.. 162 |
| | 3.11 METHODS FOR REDUCING TOXIC EFFECTS. 164 |
| | 3.11.1 Reducing Peak Absorption Following Exposure . 165 |
| | 3.11.2 Reducing Body Burden . 166 |
| | 3.11.3 Interfering with the Mechanism of Action for Toxic Effects. 167 |
| | 3.12 ADEQUACY OF THE DATABASE. 168 |
| | 3.12.1 Existing Information on Health Effects of Fluorides, Hydrogen Fluoride, and Fluorine 169 |
| | 3.12.2 Identification of Data Needs .. 173 |
| | 3.12.3 Ongoing Studies 185 |
| | 4. CHEMICAL AND PHYSICAL INFORMATION 187 |
| | 4.1 CHEMICAL IDENTITY187 |
| | 4.2 PHYSICAL AND CHEMICAL PROPERTIES. 187 |
| | 5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL. 193 |
| | 5.1 PRODUCTION .. 193 |
| | 5.2 IMPORT/EXPORT .. 194 |
| | 5.3 USE.. 199 |
| | 5.4 DISPOSAL.. 200 |
| | 6. POTENTIAL FOR HUMAN EXPOSURE .. 203 |
| | 6.1 OVERVIEW 203 |
| | 6.2 RELEASES TO THE ENVIRONMENT.. 206 |
| | 6.2.1 Air .. 209 |
| | 6.2.2 Water. 213 |
| | 6.2.3 Soil . 214 |
| | 6.3 ENVIRONMENTAL FATE.215 |
| | 6.3.1 Transport and Partitioning 215 |
| | 6.3.2 Transformation and Degradation .216 |
| | 6.3.2.1 Air . 216 |
| | 6.3.2.2 Water 217 |
| | 6.3.2.3 Sediment and Soil .. 218 |
| | 6.3.2.4 Other Media .. 218 |
| | 6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT. 218 |
| | 6.4.1 Air .. 218 |
| | 6.4.2 Water. 219 |
| | 6.4.3 Sediment and Soil 222 |
| | 6.4.4 Other Environmental Media223 |
| | 6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE . 225 |
| | 6.6 EXPOSURES OF CHILDREN.. 230 |
| | 6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES . 234 |
| | 6.8 ADEQUACY OF THE DATABASE.. 237 |
| | 6.8.1 Identification of Data Needs .. 237 |
| | 6.8.2 Ongoing Studies 241 |
| | 7. ANALYTICAL METHODS 243 |
| | 7.1 BIOLOGICAL MATERIALS.243 |
| | 7.2 ENVIRONMENTAL SAMPLES..246 |
| | 7.3 ADEQUACY OF THE DATABASE.. 251 |
| | 7.3.1 Identification of Data Needs .. 252 |
| | 7.3.2 Ongoing Studies 253 |
| | 8. REGULATIONS AND ADVISORIES ..255 |
| | 9. REFERENCES .. 265 |
| | 10. GLOSSARY . 351 |
| | APPENDICES |
| | A. ATSDR MINIMAL RISK LEVEL AND WORKSHEETS A-1 |
| | B. USER'S GUIDE B-1 |
| | C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS. C-1 |
| | D. FLUORIDE AND DENTAL CARIES ..D-1 |