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TOXICOLOGICAL PROFILE FOR CHLORINATED DIBENZO-p-DIOXINS

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723

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3466

Agency for Toxic Substances and Disease Registry

2002

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CONTENTS

FOREWORD v

QUICK REFERENCE FOR HEALTH CARE PROVIDERS vii

CONTRIBUTORS ix

PEER REVIEW xi

LIST OF FIGURES xvii

LIST OF TABLES xix

1. PUBLIC HEALTH STATEMENT 1

1.1 WHAT ARE CDDS? 1

1.2 WHAT HAPPENS TO CDDS WHEN THEY ENTER THE ENVIRONMENT? 3

1.3 HOW MIGHT I BE EXPOSED TO CDDS? 5

1.4 HOW CAN CDDS ENTER AND LEAVE MY BODY? 8

1.5 HOW CAN CDDS AFFECT MY HEALTH? 9

1.6 HOW CAN CDDs AFFECT CHILDREN? 13

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO CDDs? 14

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

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO PROTECT

HUMAN HEALTH? 16

1.10 WHERE CAN I GET MORE INFORMATION? 17

2. HEALTH EFFECTS 19

2.1 HUMAN STUDIES 19

2.1.1 Death 26

2.1.2 Systemic Effects 27

2.1.3 Immunological Effects 42

2.1.4 Neurological Effects 46

2.1.5 Reproductive Effects 49

2.1.6 Developmental Effects 52

2.1.7 Genotoxic Effects 55

2.1.8 Cancer 56

2.2. ANIMAL STUDIES 68

2.2.1 Inhalation Exposure 69

2.2.1.1 Death 69

2.2.1.2 Systemic Effects 69

2.2.1.3 Immunological Effects 69

2.2.1.4 Neurological Effects 69

2.2.1.5 Reproductive Effects 69

2.2.1.6 Developmental Effects 69

2.2.1.7 Genotoxic Effects 69

2.2.1.8 Cancer 69

2.2.2 Oral Exposure 69

2.2.2.1 Death 70

2.2.2.2 Systemic Effects 73

2.2.2.3 Immunological Effects 161

2.2.2.4 Neurological Effects 165

2.2.2.5 Reproductive Effects 166

2.2.2.6 Developmental Effects 168

2.2.2.7 Genotoxic Effects 176

2.2.2.8 Cancer 176

2.2.3 Dermal Exposure 178

2.2.3.1 Death 178

2.2.3.2 Systemic Effects 178

2.2.2.3 Immunological Effects 186

2.2.3.4 Neurological Effects 186

2.2.3.5 Reproductive Effects 186

2.2.3.6 Developmental Effects 186

2.2.3.7 Genotoxic Effects 187

2.2.3.8 Cancer 187

2.3 TOXICOKINETICS 187

2.3.1 Absorption 188

2.3.1.1 Inhalation Exposure 188

2.3.1.2 Oral Exposure 189

2.3.1.3 Dermal Exposure 190

2.3.2 Distribution 192

2.3.2.1 Inhalation Exposure 193

2.3.2.2 Oral Exposure 193

2.3.2.3 Dermal Exposure 196

2.3.3 Metabolism 197

2.3.4 Elimination and Excretion 198

2.3.4.1 Inhalation Exposure 201

2.3.4.2 Oral Exposure 201

2.3.4.3 Dermal Exposure 202

2.3.4.4 Transfer of CDDs Through the Placenta and Breast Milk 203

2.3.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models 210

2.3.5.1 Summary of PBPK Models. 213

2.3.5.2 Comparison of PBPK Models for 2,3,7,8-TCDD. 215

2.3.5.3 TCDD Models 217

2.3.5.4 Risk Assessment. 226

2.4 MECHANISMS OF ACTION 227

2.4.1 Pharmacokinetic Mechanisms 227

2.4.2 Mechanisms of Toxicity 230

2.4.3 Animal-To-Human Extrapolations 247

2.5 RELEVANCE TO PUBLIC HEALTH 252

2.6 CHILDREN’S SUSCEPTIBILITY 312

2.7 BIOMARKERS OF EXPOSURE AND EFFECT 318

2.7.1 Biomarkers Used to Identify or Quantify Exposure to CDDs 319

2.7.2 Biomarkers Used to Characterize Effects Caused by CDDs 322

2.8 INTERACTIONS WITH OTHER CHEMICALS 323

2.9 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 326

2.10 METHODS FOR REDUCING TOXIC EFFECTS 327

2.10.1 Reducing Peak Absorption Following Exposure 327

2.10.2 Reducing Body Burden 328

2.10.3 Interfering with the Mechanism of Action for Toxic Effects 329

2.11 ADEQUACY OF THE DATABASE 330

2.11.1 Existing Information on Health Effects of CDDs 330

2.11.2 Identification of Data Needs 333

2.11.4 Ongoing Studies 345

3. CHEMICAL AND PHYSICAL INFORMATION 357

3.1 CHEMICAL IDENTITY 357

3.2 PHYSICAL AND CHEMICAL PROPERTIES 357

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 369

4.1 PRODUCTION 369

4.2 IMPORT/EXPORT 371

4.3 USE 371

4.4 DISPOSAL 371

5. POTENTIAL FOR HUMAN EXPOSURE 377

5.1 OVERVIEW 377

5.2 RELEASES TO THE ENVIRONMENT 382

5.2.1 Air 390

5.2.2 Water 396

5.2.3 Soil 399

5.3 ENVIRONMENTAL FATE 400

5.3.1 Transport and Partitioning 401

5.3.2 Transformation and Degradation 419

5.3.2.1 Air 419

5.3.2.2 Water 420

5.3.2.3 Sediment and Soil 423

5.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 426

5.4.1 Air 426

5.4.2 Water 431

5.4.3 Sediment and Soil 434

5.4.4 Other Environmental Media 442

5.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 461

5.5.1 General Population 461

5.5.2 Occupational Exposure 474

5.6 EXPOSURES OF CHILDREN 477

5.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 485

5.8 ADEQUACY OF THE DATABASE 497

5.8.1 Identification of Data Needs 498

5.8.2 Ongoing Studies 502

6. ANALYTICAL METHODS 507

6.1 BIOLOGICAL SAMPLES 507

6.2 ENVIRONMENTAL SAMPLES 522

6.3 ADEQUACY OF THE DATABASE 525

6.3.1 Identification of Data Needs 526

6.3.2 Ongoing Studies 527

7. REGULATIONS AND ADVISORIES 529

8. REFERENCES 543

9. GLOSSARY 673

APPENDICES

A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS A-1

B. USER'S GUIDE B-1

C. ATSDR POLICY GUIDELINE: DIOXIN AND DIOXIN-LIKE COMPOUNDS IN SOIL C-1

D. ACRONYMS, ABBREVIATIONS, AND SYMBOLS D-1