Toxicological profiles - Polychlorinated Biphenyls

TOXICOLOGICAL PROFILE FOR POLYCHLORINATED BIPHENYLS (PCBs)......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
LIST OF FIGURES......Page 20
LIST OF TABLES......Page 22
1.1 WHAT ARE POLYCHLORINATED BIPHENYLS?......Page 26
1.2 WHAT HAPPENS TO POLYCHLORINATED BIPHENYLS WHEN THEY ENTER THE ENVIRONMENT?......Page 27
1.3 HOW MIGHT I BE EXPOSED TO POLYCHLORINATED BIPHENYLS?......Page 28
1.5 HOW CAN POLYCHLORINATED BIPHENYLS AFFECT MY HEALTH?......Page 30
1.6 HOW CAN POLYCHLORINATED BIPHENYLS AFFECT CHILDREN?......Page 32
1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO POLYCHLORINATED BIPHENYLS?......Page 34
1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED TO POLYCHLORINATED BIPHENYLS?......Page 35
1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO PROTECT HUMAN HEALTH?......Page 36
1.10 WHERE CAN I GET MORE INFORMATION?......Page 38
2.1 Background and Environmental Exposures to PCBs in the United States......Page 40
2.2 Summary of Health Effects......Page 41
2.3 Minimal Risk Levels......Page 53
3.1 INTRODUCTION......Page 59
3.2.1.2 Animal Studies......Page 114
3.2.2.1 Respiratory......Page 116
3.2.2.2 Cardiovascular......Page 120
3.2.2.3 Gastrointestinal......Page 123
3.2.2.4 Hematological......Page 125
3.2.2.5 Musculoskeletal......Page 128
3.2.2.6 Hepatic Effects......Page 129
3.2.2.7 Renal Effects......Page 147
3.2.2.8 Endocrine Effects......Page 149
3.2.2.9 Dermal Effects......Page 163
3.2.2.10 Ocular Effects......Page 168
3.2.2.11 Body Weight Effects......Page 172
3.2.3.1 Summary......Page 174
3.2.3.2 Human Studies......Page 175
3.2.3.3 Animal Studies......Page 181
3.2.4.1 Summary......Page 193
3.2.4.2 Human Studies......Page 194
3.2.4.3 Animal Studies......Page 217
3.2.5.2 Human Studies......Page 232
3.2.5.3 Animal Studies......Page 245
3.2.6.1 Summary......Page 258
3.2.6.2 Human Studies......Page 260
3.2.6.3 Animal Studies......Page 272
3.2.7.2 In Vivo Studies......Page 278
3.2.7.4 Evaluation of Genotoxicity Studies......Page 281
3.2.8.2 Human Studies......Page 283
3.2.8.3 Animal Studies......Page 308
3.3.1 Overview......Page 318
3.3.2 Health Effects in Wildlife......Page 324
3.4 TOXICOKINETICS......Page 329
3.4.1.1 Inhalation Exposure......Page 330
3.4.1.2 Oral Exposure......Page 331
3.4.1.3 Dermal Exposure......Page 337
3.4.2 Distribution......Page 340
3.4.2.1 Inhalation Exposure......Page 347
3.4.2.2 Oral Exposure......Page 348
3.4.2.4 Other Routes of Exposure......Page 351
3.4.3 Metabolism......Page 352
3.4.4.1 Inhalation Exposure......Page 358
3.4.4.2 Oral Exposure......Page 359
3.4.4.3 Dermal Exposure......Page 373
3.4.4.4 Other Routes of Exposure......Page 374
3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models......Page 375
3.4.5.1 Summary of the PBPK Model......Page 376
3.4.5.2 Description of the Model......Page 379
3.4.5.3 Discussion of the Model......Page 380
3.4.5.4 Validation of the Model......Page 386
3.4.5.5 Prediction of Congener Specific PBPK......Page 387
3.5.1 Pharmacokinetic Mechanisms......Page 389
3.5.2 Mechanisms of Toxicity......Page 394
3.5.3 Animal-to-Human Extrapolations......Page 412
3.6 ENDOCRINE DISRUPTION......Page 414
3.7 CHILDREN’S SUSCEPTIBILITY......Page 422
3.8 BIOMARKERS OF EXPOSURE AND EFFECT......Page 437
3.8.1 Biomarkers Used to Identify or Quantify Exposure to Polychlorinated Biphenyls......Page 438
3.8.2 Biomarkers Used to Characterize Effects Caused by Polychlorinated Biphenyls......Page 442
3.9 INTERACTIONS WITH OTHER CHEMICALS......Page 444
3.11 METHODS FOR REDUCING TOXIC EFFECTS......Page 454
3.11.2 Reducing Body Burden......Page 455
3.11.3 Interfering with the Mechanism of Action for Toxic Effects......Page 456
3.12.1 Existing Information on Health Effects of Polychlorinated Biphenyls......Page 457
3.12.2 Identification of Data Needs......Page 461
3.12.3 Ongoing Studies......Page 479
4.1 CHEMICAL IDENTITY......Page 488
4.2 PHYSICAL AND CHEMICAL PROPERTIES......Page 489
5.1 PRODUCTION......Page 513
5.2 IMPORT/EXPORT......Page 514
5.3 USE......Page 515
5.4 DISPOSAL......Page 518
6.1 OVERVIEW......Page 525
6.2 RELEASES TO THE ENVIRONMENT......Page 529
6.2.1 Air......Page 530
6.2.2 Water......Page 531
6.2.3 Soil......Page 534
6.3.1 Transport and Partitioning......Page 535
6.3.2.1 Air......Page 555
6.3.2.2 Water......Page 560
6.3.2.3 Sediment and Soil......Page 561
6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT......Page 575
6.4.1 Air......Page 576
6.4.2 Water......Page 585
6.4.3 Sediment and Soil......Page 592
6.4.4 Other Environmental Media......Page 595
6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE......Page 621
6.6 EXPOSURES OF CHILDREN......Page 636
6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES......Page 644
6.8 ADEQUACY OF THE DATABASE......Page 657
6.8.1 Identification of Data Needs......Page 658
6.8.2 Ongoing Studies......Page 662
7. ANALYTICAL METHODS......Page 665
7.1 BIOLOGICAL SAMPLES......Page 667
7.2 ENVIRONMENTAL SAMPLES......Page 674
7.3.1 Identification of Data Needs......Page 681
8. REGULATIONS AND ADVISORIES......Page 688
9. REFERENCES......Page 699
Case-Control Study......Page 836
Epidemiology......Page 837
Lethal Time......Page 838
Organophosphate or Organophosphorus Compound......Page 839
Reference Concentration (RfC)......Page 840
Threshold Limit Value (TLV)......Page 841
Xenobiotic......Page 842
ATSDR MINIMAL RISK LEVEL AND WORKSHEETS......Page 844
USER'S GUIDE......Page 905
ACRONYMS, ABBREVIATIONS, AND SYMBOLS......Page 913
INDEX......Page 919
APPENDIX E......Page 929
NOTE......Page 930
TABLE OF CONTENTS......Page 931
LIST OF ABBREVIATIONS......Page 932
EXECUTIVE SUMMARY......Page 933
1.2 The Expert Panel......Page 935
1.3 The Expert Panel Review Meeting......Page 936
1.4 Report Organization......Page 937
2.2 Content Issues......Page 938
3.1 Comments on Chapter 1—Public Health Statement......Page 941
3.2 Comments on Chapter 2—Health Effects......Page 942
3.2.1 Developmental Effects......Page 943
3.2.2 Neurological Effects......Page 946
3.2.3 Children’s Susceptibility......Page 948
3.2.4 Endocrine Effects......Page 950
3.2.5 Cancer......Page 953
3.2.6 Reproductive Effects......Page 960
3.2.8 Mechanisms of Action......Page 961
3.3 Comments on Chapter 3—Chemical and Physical Information......Page 962
3.4 Comments on Chapter 4—Production, Import/Export, Use, and Disposal......Page 963
3.5 Comments on Chapter 5—Potential for Human Exposure......Page 964
3.6 Comments on Chapter 6 to Chapter 9......Page 966
3.7.1 Tryphonas Study (Tryphonas et al. 1989, 1991b)......Page 967
3.7.2 Studies Reviewed by Tilson et al. (1990)......Page 972
3.7.3 Rice Studies......Page 974
3.7.4 Additional Comments on MRLs......Page 975
4.0 REFERENCES......Page 977
List of Participants and Observers for the Expert Panel Review for PCBs (September 27 - 29, 1999)......Page 984
Agenda for the Expert Panel Review of the Toxicological Profile for PCBs......Page 993