Toxicological profiles - Chlorinated dibenzo-p-dioxins

TOXICOLOGICAL PROFILE FOR CHLORINATED DIBENZO-p-DIOXINS......Page 1
CONTENTS......Page 14
DISCLAIMER......Page 2
UPDATE STATEMENT......Page 3
FOREWORD......Page 5
QUICK REFERENCE FOR HEALTH CARE PROVIDERS......Page 7
CONTRIBUTORS......Page 10
PEER REVIEW......Page 12
PAST PEER-REVIEWS......Page 13
LIST OF FIGURES......Page 18
LIST OF TABLES......Page 20
1.1 WHAT ARE CDDs?......Page 22
1.2 WHAT HAPPENS TO CDDs WHEN THEY ENTER THE ENVIRONMENT?......Page 24
1.3 HOW MIGHT I BE EXPOSED TO CDDs?......Page 26
1.4 HOW CAN CDDs ENTER AND LEAVE MY BODY?......Page 29
1.5 HOW CAN CDDs AFFECT MY HEALTH?......Page 30
1.6 HOW CAN CDDs AFFECT CHILDREN?......Page 34
1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO CDDs?......Page 35
1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED TO CDDS?......Page 36
1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO PROTECT HUMAN HEALTH?......Page 37
1.10 WHERE CAN I GET MORE INFORMATION?......Page 38
2.1 HUMAN STUDIES......Page 40
2.1.1 Death......Page 48
2.1.2 Systemic Effects......Page 49
2.1.3 Immunological Effects......Page 64
2.1.4 Neurological Effects......Page 68
2.1.5 Reproductive Effects......Page 71
2.1.6 Developmental Effects......Page 75
2.1.7 Genotoxic Effects......Page 78
2.1.8 Cancer......Page 79
2.2. ANIMAL STUDIES......Page 90
2.2.2 Oral Exposure......Page 92
2.2.2.1 Death......Page 93
2.2.2.2 Systemic Effects......Page 96
2.2.2.3 Immunological Effects......Page 183
2.2.2.4 Neurological Effects......Page 188
2.2.2.5 Reproductive Effects......Page 189
2.2.2.6 Developmental Effects......Page 191
2.2.2.7 Genotoxic Effects......Page 198
2.2.2.8 Cancer......Page 199
2.2.3.1 Death......Page 200
2.2.3.2 Systemic Effects......Page 201
2.2.3.6 Developmental Effects......Page 209
2.3 TOXICOKINETICS......Page 210
2.3.1.1 Inhalation Exposure......Page 211
2.3.1.2 Oral Exposure......Page 212
2.3.1.3 Dermal Exposure......Page 213
2.3.2 Distribution......Page 215
2.3.2.2 Oral Exposure......Page 216
2.3.2.3 Dermal Exposure......Page 219
2.3.3 Metabolism......Page 220
2.3.4 Elimination and Excretion......Page 221
2.3.4.2 Oral Exposure......Page 224
2.3.4.3 Dermal Exposure......Page 225
2.3.4.4 Transfer of CDDs Through the Placenta and Breast Milk......Page 226
2.3.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models......Page 233
2.3.5.1 Summary of PBPK Models.......Page 236
2.3.5.2 Comparison of PBPK Models for 2,3,7,8-TCDD.......Page 238
2.3.5.3 TCDD Models......Page 240
2.3.5.4 Risk Assessment.......Page 249
2.4.1 Pharmacokinetic Mechanisms......Page 250
2.4.2 Mechanisms of Toxicity......Page 253
2.4.3 Animal-To-Human Extrapolations......Page 269
2.5 RELEVANCE TO PUBLIC HEALTH......Page 275
2.6 CHILDREN’S SUSCEPTIBILITY......Page 335
2.7 BIOMARKERS OF EXPOSURE AND EFFECT......Page 340
2.7.1 Biomarkers Used to Identify or Quantify Exposure to CDDs......Page 341
2.7.2 Biomarkers Used to Characterize Effects Caused by CDDs......Page 344
2.8 INTERACTIONS WITH OTHER CHEMICALS......Page 345
2.10 METHODS FOR REDUCING TOXIC EFFECTS......Page 349
2.10.2 Reducing Body Burden......Page 350
2.11 ADEQUACY OF THE DATABASE......Page 352
2.11.1 Existing Information on Health Effects of CDDs......Page 353
2.11.2 Identification of Data Needs......Page 356
2.11.4 Ongoing Studies......Page 368
3.2 PHYSICAL AND CHEMICAL PROPERTIES......Page 380
4.1 PRODUCTION......Page 393
4.4 DISPOSAL......Page 395
5.1 OVERVIEW......Page 401
5.2 RELEASES TO THE ENVIRONMENT......Page 407
5.2.1 Air......Page 416
5.2.2 Water......Page 422
5.2.3 Soil......Page 426
5.3 ENVIRONMENTAL FATE......Page 427
5.3.1 Transport and Partitioning......Page 428
5.3.2.1 Air......Page 448
5.3.2.2 Water......Page 449
5.3.2.3 Sediment and Soil......Page 452
5.4.1 Air......Page 455
5.4.2 Water......Page 460
5.4.3 Sediment and Soil......Page 463
5.4.4 Other Environmental Media......Page 472
5.5.1 General Population......Page 494
5.5.2 Occupational Exposure......Page 509
5.6 EXPOSURES OF CHILDREN......Page 512
5.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES......Page 521
5.8 ADEQUACY OF THE DATABASE......Page 534
5.8.1 Identification of Data Needs......Page 535
5.8.2 Ongoing Studies......Page 539
6.1 BIOLOGICAL SAMPLES......Page 544
6.2 ENVIRONMENTAL SAMPLES......Page 559
6.3.1 Identification of Data Needs......Page 563
6.3.2 Ongoing Studies......Page 565
7. REGULATIONS AND ADVISORIES......Page 566
8. REFERENCES......Page 581
Case Report......Page 711
Immediately Dangerous to Life or Health (IDLH)......Page 712
Modifying Factor (MF)......Page 713
Pharmacokinetic Model......Page 714
Reportable Quantity (RQ)......Page 715
ATSDR MINIMAL RISK LEVELS AND WORKSHEETS......Page 716
MRL WORKSHEET......Page 718
ATSDR POLICY GUIDELINE: DIOXIN AND DIOXIN-LIKE COMPOUNDS IN SOIL......Page 726
POLICY GUIDELINE......Page 727
BACKGROUND FOR POLICY GUIDELINE......Page 731
WHERE TO FIND MORE INFORMATION......Page 734
REFERENCES......Page 735
APPENDIX 1 - GLOSSARY......Page 736
USER'S GUIDE......Page 738
ACRONYMS, ABBREVIATIONS, AND SYMBOLS......Page 746