Health Risk Analyses for Dioxin, Dose-Response Uncertainty, Toxicity Values, and Cumulative Risk

1. Health Risk Analyses for Dioxin, Dose-Response Uncertainty, Toxicity Values, and Cumulative Risk Molly Finster Environmental Science Division (EVS) July 23, 2008

2. Presentation Overview • Collaborative IAG • Introduction to Dioxin • EPA Dioxin Assessment Chronology • Dioxin Project • Current Work • Acknowledgements

3. Collaborative Interagency Agreement • EPA-NCEA and DOE-Argonne • Purpose: Advance risk analyses to support overall health protection • Interrelated technical areas • Dioxin and dioxin-like compounds (DLCs) • Dose-response uncertainty characterization • Toxicity values • Cumulative risk assessment

4. What is Dioxin? • “Dioxin” is a general term that describes a family of hundreds of chemicals that have a similar chemical structure and induce harm through a similar mechanism • Most toxic compound is 2,3,7,8-tetrachlorodibenzo-p-dioxin or TCDD • toxicity of other dioxins and chemicals that act like dioxin (e.g. PCBs) are measured in relation to TCDD • toxic equivalency factors (TEFs) • also, the most well-studied dioxin compound

5. Where does Dioxin come from? • Formed by burning chlorine-based compounds with hydrocarbons: • waste incineration, forest fires, pulp and paper mills, chemical and pesticide manufacturing • Environmental levels have been declining since the early 1970’s and have been the subject of a number of federal and state regulations and clean-up actions • However, current exposure levels still remain a concern to communities and organizations because of • potential toxicity combined with • relatively long half-lives in the environment & in human tissues

6. Why do we care about Dioxin? • Characterized by EPA as likely human carcinogen • concern that it might increase the risk of cancer at (higher) background levels of exposure in general US population • can also cause many non-cancer effects: • reproductive system and developmental changes • at levels 100x times lower than those associated with cancer effects • alter immune system • interfere with hormonal systems • Long-standing public fears: • primary toxic component of Agent Orange (Vietnam vets) • evacuations at Love Canal, Times Beach (MO), Seveso (Italy) • found at WTC

7. EPA Dioxin Assessment Chronology • 1985: Dioxin assessment • May 1991: Charge from EPA Administrator to update • 1991-1994: Comprehensive update:development of topical chapters, peer review • 1995: EPA Science Advisory Board (SAB) review • 1995-2000: Revision, internal and interagency review • 2000-2001: SAB re-review • 2002-2004: Revision, internal and interagency review • 2004-2006: National Academy of Sciences (NAS) review • 2008-2011: Respond to NAS comments: complete the assessment

8. Dioxin Project Scope of Work: 2008 • Assess key technical issues and develop a scientific foundation for the EPA technical response to the NAS review of the dioxin reassessment • 3 areas for substantial improvement: • justification of dose-response models for cancer and noncancer endpoints • transparency and clarity in selection of data sets for analysis • transparency, thoroughness, and clarity in quantitative uncertainty analysis • Identify and evaluate current scientific information • dioxin literature has continued its significant expansion since the reassessment document was last revised (in 2003)

9. Dioxin Project Scope of Work: 2008 • Involve experts and solicit public input on key studies and technical issues • Federal Register Notice (targeted for August 2008): list of candidate studies for public review & addition • Expert panel meeting (targeted for November 2008): identify key issues & studies to support the response to comments • Summarize inputs to guide the technical work plan for completing the dioxin assessment

10. Literature Search Strategy & Implementation • Search the literature and pursue additional information to identify key studies, technical issues, and expertise • comprehensiveness is crucial • previous EPA approach not systematic (e.g., limiting criteria applied for existing modeling approaches) • extensive earlier literature also in play • extensive integration across technical topics • Obtain and evaluate potentially relevant studies, and select studies for detailed evaluation • Review studies, extracting key toxicity data, and synthesize information to frame initial expert input on key studies, issues, and approaches for addressing those issues

11. ~500 terms across 14 endpoints & 8 technical areas Thousands of candidate papers identified for 7 endpoints; > 3,000 from 2000-2008 screened & coded  600+ retrieved 4,500 papers retrieved (past 6 meetings)  screened to 660 Sheer Volume of Dioxin Literature

12. Sheer Volume of Dioxin Literature

13. Extracting Key Toxicity Data

14. Extracting Key Toxicity Data

15. Synthesizing and Presenting Information Exposure-Response Array for Selected Toxicity Data (Grouped by Endpoint )

16. Acknowledgements • Summer Interns: • Argonne: • Maryka Bhattacharyya (STA) • Young-Soo Chang • Andrew Davidson (STA) • Margaret MacDonell • Dave Peterson • NCEA: • Belinda Hawkins • Janet Hess-Wilson • Glenn Rice • Jeff Swartout • Linda Teuschler • Bette Zwayer • Caitlin Burke • Amy Green • Jonathan Harris • Vivian Nwachukwu • Sameera Rahman • James Shannon • David Wyker • Family