Document yrz9Qx09JV1My14jw2ZjJ6EaE

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460 DEC 2 2 2011 Timothy J. Buckley, Ph.D. Chairman, Dioxin Review Panel Science Advisory Board U.S. Environmental Protection Agency 1200 Pennsylvania Avenue, NW Washington, D.C. 20460 THE ADMINISTRATOR Dear Dr. Buckley: Thank you for your August 26, 2011, letter in which you provide the Science Advisory Board Dioxin Review Panel's comments on the U.S. Environmental Protection Agency's May 2010 draft report, EPA's Reanalysis o f Key Issues Related to Dioxin Toxicity and Response to NAS Comments. The EPA greatly appreciates the expert panel's thorough review and constructive comments. As we revise the draft reanalysis, we are carefully considering your recommendations and the public comments submitted to the EPA. Based on the panel's thoughtful review, the EPA has decided to separate the draft reanalysis into two volumes: Volume 1, a non-cancer assessment, and Volume 2, a cancer assessment and quantitative uncertainty analysis. The EPA made this decision after carefully considering the recommendations in the Science Advisory Board's report and the agency's needs for dioxin-toxicity values. We are currently revising Volume 1, which we anticipate completing by the end of January 2012. After Volume 1 is final, the EPA will focus on completing Volume 2 as expeditiously as possible. In revising and completing Volume 1 of the dioxin reanalysis, the EPA will give full consideration to the panel's comments and recommendations and the public's comments, with the exception of those pertaining specifically to the cancer assessment. Volume 1 will include: The EPA's study-inclusion criteria and study-selection process for both the non-cancer and cancer dose response assessments for 2,3,7,8- tetrachlorodibenzo-p-dioxin or TCDD; Choice of kinetic model; Derivation of the non-cancer RfD for TCDD; and A qualitative discussion of uncertainties in the RfD with a quantitative uncertainty analysis. Based on the Science Advisory Board's recommendations, the EPA, in its efforts to complete Volume 1, also will: Revise and clarify the discussion of the criteria and considerations used to evaluate the suitability of the epidemiological studies and animal bioassays for TCDD dose-response assessment; Systematically evaluate the epidemiologic studies and rodent bioassays relevant to TCDD dose-response assessment based on the revised criteria and considerations; Internet Address (URL) http://www.epa.gov Recycled/Recyclable Printed with Vegetable Oil Based Inks on 100% Postconsumer, Process Chlorine Free Recycled Paper  Further evaluate the basis of the Hill parameter used in the TCDD physiologically based pharmacokinetic model that simulates TCDD blood concentrations, the dose metric used in all dose-response analyses for TCDD; Conduct a sensitivity analysis on the PBPK model; Conduct a quantitative uncertainty analysis of the decisions made in developing points of departure for TCDD RfD derivation. Your advice and detailed comments have been extremely valuable in guiding us as we complete the reanalysis. Once again, I offer my thanks to the Science Advisory Board and the Dioxin Review Panel members for all your hard work in helping to ensure that the EPA uses best science in this important assessment. Sincerely, cc: Paul Anastas Becki Clark Annette Gatchett Lynn Flowers Glenn Rice Kacee Deener Jeff Swartout Linda Teuschler Belinda Hawkins UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460 Deborah L. Swackhamer, Ph.D. Chairwoman Science Advisory Board U.S. Environmental Protection Agency 1200 Pennsylvania Avenue, NW Washington, D.C. 20460 DEC 2 2 2011 THE ADMINISTRATOR Dear Dr. Swackhamer: Thank you for your August 26, 2011, letter in which you provide the Science Advisory Board Dioxin Review Panel's comments on the U.S. Environmental Protection Agency's May 2010 draft report, EPA's Reanalysis o f Key Issues Related to Dioxin Toxicity and Response to NAS Comments. The EPA greatly appreciates the expert panel's thorough review and constructive comments. As we revise the draft reanalysis, we are carefully considering your recommendations and the public comments submitted to the EPA. Based on the panel's thoughtful review, the EPA has decided to separate the draft reanalysis into two volumes: Volume 1, a non-cancer assessment, and Volume 2, a cancer assessment and quantitative uncertainty analysis. The EPA made this decision after carefully considering the recommendations in the Science Advisory Board's report and the agency's needs for dioxin-toxicity values. We are currently revising Volume 1, which we anticipate completing by the end of January 2012. After Volume 1 is final, the EPA will focus on completing Volume 2 as expeditiously as possible. In revising and completing Volume 1 of the dioxin reanalysis, the EPA will give full consideration to the panel's comments and recommendations and the public's comments, with the exception of those pertaining specifically to the cancer assessment. Volume 1 will include: The EPA's study-inclusion criteria and study-selection process for both the non-cancer and cancer dose response assessments for 2,3,7,8- tetrachlorodibenzo-/>dioxin or TCDD; Choice of kinetic model; Derivation of the non-cancer RfD for TCDD; and A qualitative discussion of uncertainties in the RfD with a quantitative uncertainty analysis. Based on the Science Advisory Board's recommendations, the EPA, in its efforts to complete Volume 1, also will: Revise and clarify the discussion of the criteria and considerations used to evaluate the suitability of the epidemiological studies and animal bioassays for TCDD dose-response assessment; Systematically evaluate the epidemiologic studies and rodent bioassays relevant to TCDD dose-response assessment based on the revised criteria and considerations; Internet Address (URL) http://www.epa.gov Recycled/Recyclable Printed with Vegetable Oil Based Inks on 100% Postconsumer, Process Chlorine Free Recycled Paper  Further evaluate the basis of the Hill parameter used in the TCDD physiologically based pharmacokinetic model that simulates TCDD blood concentrations, the dose metric used in all dose-response analyses for TCDD; Conduct a sensitivity analysis on the PBPK model; Conduct a quantitative uncertainty analysis of the decisions made in developing points of departure for TCDD RfD derivation. Your advice and detailed comments have been extremely valuable in guiding us as we complete the reanalysis. Once again, I offer my thanks to the Science Advisory Board and the Dioxin Review Panel members for all your hard work in helping to ensure that the EPA uses best science in this important assessment. Sincerely, cc: Paul Anastas Becki Clark Annette Gatchett Lynn Flowers Glenn Rice Kacee Deener Jeff Swartout Linda Teuschler Belinda Hawkins