Health risks from dioxin and related compounds : evaluation of the EPA reassessment

Contents Copyright © National Academy of Sciences. All rights reserved. Health Risks from Dioxin and Related Compounds: Evaluation of the EPA Reassessment http://www.nap.edu/catalog/11688.html xxiv CONTENTS 3 TOXIC EQUIVALENCY FACTORS 75 Dioxin-like Compounds, 75 Major Issues, Assumptions, and Uncertainties, 76 Key Studies and Publications to Be Included, 85 Conclusions and Recommendations, 86 4 EXPOSURE ASSESSMENT 90 Assessment Procedures, 90 Overview and Commentary on EPA’s Exposure Characterization, 91 Committee Findings, 99 Conclusions and Recommendations, 105 5 CANCER 108 Qualitative Evaluation of Carcinogenicity, 108 Quantitative Considerations in Assessing TCDD, Other Dioxins, and DLC Carcinogenicity, 121 Conclusions and Recommendations, 140 6 NONCANCER END POINTS 144 Immune Function, 144 Conclusions and Recommendations on the Immunotoxicity of TCDD, Other Dioxins, and DLCs, 153 Reproduction and Development, 154 Other Noncancer End Points, 169 Conclusions and Recommendations on the Reproductive, Developmental, and Other Noncancer End Points of TCDD, Other Dioxins, and DLCs, 173 7 REVIEW OF RISK CHARACTERIZATION 175 Review, 175 Conclusions and Recommendations, 186 8 CONCLUSIONS AND RECOMMENDATIONS 188 Classification of TCDD as Carcinogenic to Humans, 188 Use of Low-Dose Linear Versus Threshold (Nonlinear) Extrapolation Models for Quantitative Cancer Risk Estimations, 190 Use of the 1% Response Level As a Point of Departure for Low-Dose Risk Estimation, 190 Characterization of Uncertainty for Risk Estimates, 192 Use of Toxic Equivalency Factors for Risk Estimation of DLCs and Mixture of DLCs, 193 Use of Body Burden As the Primary Dose Metric for Cross-Species Extrapolation, 193 Copyright © National Academy of Sciences. All rights reserved. Health Risks from Dioxin and Related Compounds: Evaluation of the EPA Reassessment http://www.nap.edu/catalog/11688.html CONTENTS xxv EPA’s Exposure Assessment for TCDD, Other Dioxins, and DLCs in the United States, 194 EPA’s Evaluation of Immunotoxicity of TCDD, Other Dioxins, and DLCs, 194 EPA’s Evaluation of Reproductive and Developmental Toxicity of TCDD, Other Dioxins, and DLCs, 195 EPA’s Evaluation of Other Toxic End Points, 195 EPA’s Overall Approach to Risk Characterization, 196 REFERENCES 199 APPENDIXES A Biographical Information on Committee Members, 227 B EPA’s 2005 Guidelines for Carcinogen Risk Assessment, 236 FIGURES S-1 Conceptual illustration of the effect of the selection of the point of departure and of the mathematical model used to extrapolate below the point of departure on the risk estimate, 5, 15 1-1 Benzene ring (a) with conjugated bonds and (b) with inner ring depicting conjugated bonds, 31 1-2 Double benzene ring structures of (a) dioxins and (b) furans, 31 1-3 Biphenyl ring structure of PCBs, 31 1-4 Examples of toxic PCDDs, PCDFs, and PCBs of interest in the Reassessment, 32 2-1 Vmax, 69 5-1 Possible mechanism for TCDD hepatocarcinogenicity, 118 5-2 Range of plausible CSF values: Consideration of parameter confidence intervals only, 140