TOXICOLOGICAL PROFILE FOR STRONTIUM

3,08
MB

445
stron

3469
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..xi

PEER REVIEW .xiii

CONTENTS.. xv

LIST OF FIGURES .xix

LIST OF TABLESxxi

1. PUBLIC HEALTH STATEMENT. 1

1.1 WHAT IS STRONTIUM?.. 1

1.2 WHAT HAPPENS TO STRONTIUM WHEN IT ENTERS THE ENVIRONMENT? . 3

1.3 HOW MIGHT I BE EXPOSED TO STRONTIUM? 4

1.4 HOW CAN STRONTIUM ENTER AND LEAVE MY BODY?.. 5

1.5 HOW CAN STRONTIUM AFFECT MY HEALTH?. 6

1.6 HOW CAN STRONTIUM AFFECT CHILDREN? . 8

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO STRONTIUM? 9

1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED TO

STRONTIUM? . 10

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO PROTECT

HUMAN HEALTH?. 11

1.10 WHERE CAN I GET MORE INFORMATION? 12

2. RELEVANCE TO PUBLIC HEALTH .15

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO STRONTIUM IN THE UNITED

STATES.. 15

2.2 SUMMARY OF HEALTH EFFECTS.. 16

2.3 MINIMAL RISK LEVELS . 23

3. HEALTH EFFECTS.. 27

3.1 INTRODUCTION.. 27

3.2 DISCUSSION OF HEALTH EFFECTS OF STABLE STRONTIUM BY ROUTE OF EXPOSURE..

31

3.2.1 Inhalation Exposure . 33

3.2.1.1 Death 33

3.2.1.2 Systemic Effects. 33

3.2.1.3 Immunological and Lymphoreticular Effects . 34

3.2.1.4 Neurological Effects.34

3.2.1.5 Reproductive Effects34

3.2.1.6 Developmental Effects 34

3.2.1.7 Cancer . 35

3.2.2 Oral Exposure . 35

3.2.2.1 Death 36

3.2.2.2 Systemic Effects. 36

3.2.2.3 Immunological and Lymphoreticular Effects . 58

3.2.2.4 Neurological Effects.58

3.2.2.5 Reproductive Effects58

3.2.2.6 Developmental Effects 58

3.2.2.7 Cancer . 59

3.2.3 Dermal Exposure .. 59

3.2.3.1 Death 60

3.2.3.2 Systemic Effects. 60

3.2.3.3 Immunological and Lymphoreticular Effects . 60

3.2.3.4 Neurological Effects.60

3.2.3.5 Reproductive Effects60

3.2.3.6 Developmental Effects 60

3.2.3.7 Cancer . 60

3.2.4 Other Routes of Exposure. 60

3.3 DISCUSSION OF HEALTH EFFECTS OF RADIOACTIVE STRONTIUM BY ROUTE OF

EXPOSURE.. 62

3.3.1 Inhalation Exposure . 63

3.3.1.1 Death 64

3.3.1.2 Systemic Effects. 65

3.3.1.3 Immunological and Lymphoreticular Effects . 73

3.3.1.4 Neurological Effects.74

3.3.1.5 Reproductive Effects 74

3.3.1.6 Developmental Effects 74

3.3.1.7 Cancer . 74

3.3.2 Oral Exposure . 76

3.3.2.1 Death 77

3.3.2.2 Systemic Effects. 80

3.3.2.3 Immunological and Lymphoreticular Effects . 93

3.3.2.4 Neurological Effects.94

3.3.2.5 Reproductive Effects94

3.3.2.6 Developmental Effects 95

3.3.2.7 Cancer . 97

3.3.3 External Exposure.. 100

3.3.3.1 Death . 101

3.3.3.2 Systemic Effects..101

3.3.3.3 Immunological and Lymphoreticular Effects .. 108

3.3.3.4 Neurological Effects..108

3.3.3.5 Reproductive Effects.108

3.3.3.6 Developmental Effects . 108

3.3.3.7 Cancer .. 108

3.3.4 Other Routes of Exposure..110

3.4 GENOTOXICITY . 113

3.5 TOXICOKINETICS. 118

3.5.1 Absorption . 118

3.5.1.1 Inhalation Exposure ..118

3.5.1.2 Oral Exposure 120

3.5.1.3 Dermal Exposure.123

3.5.2 Distribution 125

3.5.2.1 Inhalation Exposure ..125

3.5.2.2 Oral Exposure 126

3.5.2.3 Dermal Exposure.129

3.5.3 Metabolism 129

3.5.3.1 Inhalation Exposure ..130

3.5.3.2 Oral Exposure 130

3.5.3.3 Dermal Exposure.130

3.5.4 Elimination and Excretion .130

3.5.4.1 Inhalation Exposure ..130

3.5.4.2 Oral Exposure 131

3.5.4.3 Dermal Exposure.132

3.5.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models. 132

3.6 MECHANISMS OF ACTION 147

3.6.1 Pharmacokinetic Mechanisms . 147

3.6.2 Mechanisms of Toxicity .150

3.6.3 Animal-to-Human Extrapolations.. 154

3.7 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS 155

3.8 CHILDREN’S SUSCEPTIBILITY.. 156

3.9 BIOMARKERS OF EXPOSURE AND EFFECT 162

3.9.1 Biomarkers Used to Identify or Quantify Exposure to Strontium . 163

3.9.2 Biomarkers Used to Characterize Effects Caused by Strontium 164

3.10 INTERACTIONS WITH OTHER CHEMICALS 164

3.11 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 165

3.12 METHODS FOR REDUCING TOXIC EFFECTS.. 167

3.12.1 Reducing Peak Absorption Following Exposure.. 168

3.12.2 Reducing Body Burden . 170

3.12.3 Interfering with the Mechanism of Action for Toxic Effects . 173

3.13 ADEQUACY OF THE DATABASE.. 173

3.13.1 Existing Information on Health Effects of Strontium. 173

3.13.2 Identification of Data Needs176

3.13.3 Ongoing Studies 187

4. CHEMICAL, PHYSICAL, and RADIOLOGICAL INFORMATION .. 189

4.1 CHEMICAL IDENTITY 189

4.2 PHYSICAL, CHEMICAL, AND RADIOLOGICAL PROPERTIES. 189

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL. 199

5.1 PRODUCTION .. 199

5.2 IMPORT/EXPORT .. 200

5.3 USE.. 200

5.4 DISPOSAL.. 201

6. POTENTIAL FOR HUMAN EXPOSURE .. 205

6.1 OVERVIEW 205

6.2 RELEASES TO THE ENVIRONMENT.. 208

6.2.1 Air . 208

6.2.2 Water 213

6.2.3 Soil 213

6.3 ENVIRONMENTAL FATE.214

6.3.1 Transport and Partitioning . 214

6.3.2 Transformation and Degradation 217

6.3.2.1 Air 219

6.3.2.2 Water. 219

6.3.2.3 Sediment and Soil ..219

6.3.2.4 Other Media .. 220

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT. 220

6.4.1 Air . 220

6.4.2 Water 222