Location: Noblis, Falls Church, VA Beyond Science and Decisions: From Problem Formulation to Dose-Response. Workshop III Date: May 4-6th, 2011 Location: Noblis, Falls Church, VA ARA Workshop III

Introduction Dose-Response Advisory Committee (DRAC) Alliance for Risk Assessment (ARA) Steering Committee Sponsors

Dose-Response Advisory Committee Rick Becker, American Chemistry Council Michael Dourson, Toxicology Excellence for Risk Assessment (TERA) Julie Fitzpatrick, Environmental Protection Agency Roberta Grant, Texas Commission on Environmental Quality (TCEQ) Lynne Haber, TERA Michael Honeycutt, TCEQ Lynn H. Pottenger, The Dow Chemical Company Jennifer Seed, Environmental Protection Agency Dose-Response Advisory Committee (DRAC). The workshop sponsors are composed of federal, state, industry, and NGO organizations.  The Dose-Response Advisory Committee interacts with these various sponsors in the development of workshop structure and charge questions, and recruitment of presenters. The DRAC will have the final decision on workshop structure, presenters, and content, after consultation with the ARA Steering Committee.

ARA Steering Committee Barbara Harper, Confederated Tribes of the Umatilla Indian Reservation William Hayes, State of Indiana Bette Meek, University of Ottawa/Health Canada (liaison with the DRAC) Anita Meyer, United States Army Corps of Engineers Edward Ohanian, United States Environmental Protection Agency Ruthann Rudel, Silent Spring Phil Wexler, National Library of Medicine Michael Dourson, Toxicology Excellence for Risk Assessment (recused) Michael Honeycutt, Texas Commission on Environmental Quality (recused) Steering Committee. The Alliance for Risk Assessment Steering Committee (SC) will provide oversight of the workshop series.  The Steering Committee will advise the DRAC on charge questions and will have the final decision on members of the Expert Panel after a review of all nominations.  The SC consists of a broad range of representatives from state, tribal, and federal government, academia, and environmental NGOs.

45 sponsors and collaborators: 11 government agencies Thanks to our sponsors! 45 sponsors and collaborators: 11 government agencies 11 industry groups 7 scientific societies 8 non-profit organizations/consortia 8 consulting groups Sponsors:     Academy of Toxicological Sciences •             American Chemistry Council     •             American Petroleum Institute •             American Water Works Association •             Center for Food Safety and Applied Nutrition (US Food and Drug Administration) •             CONSORTIUM FOR ENVIRONMENTAL RISK MANAGEMENT, LLC (CERM) •             CropLife America •             Dose Response Specialty Group (Society for Risk Analysis) •             ENVIRON •             Georgia Department of Natural Resources (EPD) •             Georgia Pacific •             GRADIENT •             Hamner Institutes •             Hawai’i Department of Health (HEER) •             Human Toxicology Project Consortium •             Illinois Environmental Protection Agency •             Indiana Department of Environmental Management •             INDUSTRIAL ECONOMICS, INCORPORATED   •             International Copper Association •             International Society of Regulatory Toxicology and Pharmacology •             The LifeLine Group •             Mickey Leland National Urban Air Toxics Research Center •             Minnesota Pollution Control Agency (Environmental Analysis & Outcomes Division) •             Naphthalene Council •             National Center for Toxicological Research •             New Zealand Ministry of Health •             Nickel Producers Environmental Research Association •             Noblis •             NSF International •             Ohio Environmental Protection Agency •             PASTOR, BEHLING & WHEELER, LLC •             Regulatory and Safety Evaluation Specialty Section (Society of Toxicology) •             Risk Assessment Specialty Section (Society of Toxicology) •             SAPPHIRE GROUP •             SC Johnson & Son •             Society for Risk Analysis •             Society of Toxicology •             SUMMIT TOXICOLOGY •             TED SIMON, LLC •             Texas Association of Business •             Texas Chemical Council •             Texas Commission on Environmental Quality •             Texas Industry Project •             Toxicology Excellence for Risk Assessment •             U.S. Environmental Protection Agency *With financial support from Health Canada

Purpose Through the development and application of case studies, to additionally evolve the methodologies in specific areas and crosscutting issues raised by Science and Decisions Advancing Risk Assessment Workshop Background & Purpose This workshop series is a continuation of the discussion set forth by the National Academy of Science (2009) Science and Decisions: Advancement of Risk Assessment, toward a unified approach to dose response assessment. Conducted under the aegis of the Alliance for Risk Assessment (ARA), a series of three workshops is underway. The workshops will be lead by an Expert Panel, and will focus on biological and statistical issues that relate to dose-response assessment. Evaluation of dose-response assessment techniques will be based on case studies. The first workshop was devoted to brainstorming and selection of case studies to evaluate proposed dose-response assessment techniques and utility in different problem formulations. In the second workshop, the Expert Panel will lead a discussion and evaluation of case study results. A third workshop scheduled for March of 2011 will seek consensus on a guidance document highlighting key considerations for applying dose-response techniques for common risk assessment applications.

Series of Three Workshops Workshop I Texas Commission on Environmental Quality, March 16-18, 2010 Workshop II Crystal City, Virginia (in tandem with the Federal & State Risk Assessment & Toxicology Committee), October 11-13, 2010 Workshop III Noblis; Falls Church, Virginia, May 4-6, 2011

Overview of Workshop Objectives Build off the NAS (2009) report to develop practical guidance for use by risk managers at a variety of levels states, regional managers, a variety of agencies, and industry for risk assessment techniques applicable to specific problem formulations. Implement a multi-stakeholder approach to share information, ideas, and techniques in support of developing practical, problem-driven risk assessment guidance. Specific Workshop Objectives:   Identify useful dose-response techniques for specified problem formulations, including characterization of assumptions, strengths and limitations, and how the techniques address key considerations in the dose-response. These techniques should appropriately reflect the relevant biology (including the biology of thresholds), and mode of action information, at a level of detail appropriate for the problem formulation. Provide methods to explicitly address human variability in cancer assessment, and enhance the consideration of human variability in noncancer assessment, including explicit consideration of underlying disease processes. Identify methods for calculating the probability of response for noncancer endpoints. Develop peer reviewed publications and/or a guidance document that will serve as a resource for regulators and scientists to refer to for guidance on key considerations for applying selected dose-response techniques for various problem formulations, with suggested techniques and resources.

Workshop Materials Workshop Notebook Online Background Agenda and Logistics Bios Case Study Summaries Online Framework Full Case Studies Presentation Slides

Housekeeping Look around now for exits in case of fire Cell phone reminder.... Mid-morning and afternoon breaks Lunch speakers scheduled and lunches provided on Wednesday and Thursday The sessions are being webcast so remember there is a second audience listening on the phone. Please be mindful of their participation: Use the mics to facilitate listening for those on webcast Only one person speaking at a time Identify yourself with name and affiliation when speaking

Beyond Science and Decisions: From Problem Formulation to Dose-Response. Workshop I Date: March 16-18, 2010 Location: Texas Commission on Environmental Quality

Workshop I Summary 60 participants with more than 100 participants via webcast Brainstorming Ongoing risk assessment activities Perspectives on the NAS (2008) Silver Book Selection of case studies Consideration and selection of case studies Focus on the principles of the methodology, not specific chemicals

Workshop II/III Expert Panel Provide guidance during the workshops Evaluate the case studies during Workshop II/III Use case studies to evolve methodologies and address cross- cutting issues raised in NAS Science & Decisions report Balance across affiliation & expertise Risk assessment and Toxicology

Panel Selection Process Announcement of workshops, with a call for Panel nominations DRAC also nominated panel member candidates ARA Steering Committee reviewed candidates and developed a prioritized list of nominees Invitations were sent to a total of 27 people Particular effort was made to include people from the NAS, 2009 Panel & environmental NGOs

Workshop II/III Expert Panel 3 from the US Federal Government, with 2 from EPA 2 from industry 2 from academia 1 from state government, and 1 state government emeritus 2 from nonprofit groups 1 consultant 2 are members of the NAS Science & Decisions Panel

Expert Panel for Workshop III Michael Bolger, U.S. Food and Drug Administration (FDA) James S. Bus, The Dow Chemical Company John Christopher, CH2M/Hill Rory Conolly, U.S EPA National Health and Environmental Effects Research Laboratory Mike Dourson, Toxicology Excellence for Risk Assessment (TERA) Adam M. Finkel, UMDNJ School of Public Health (NAS 2009 Panel) R. Jeffrey Lewis, ExxonMobil Biomedical Sciences, Inc. Randy Manning,Georgia Department of Natural Resources (Environmental Protection Division) Bette Meek, McLaughlin Centre for Population Health Risk Assessment, University of Ottawa (Chairperson) Greg Paoli, Risk Sciences International (NAS 2009 Panel) Rita Schoeny, U.S. EPA Office of Water Paul Moyer, Minnesota Department of Health (MDH) and William Hayes, Indiana Department of Environmental Management were originally on the panel, but had to withdraw due to new job responsibilities

Activities between Workshops II & III Panel reviewed the case studies A draft risk framework was developed and posted on the ARA website New case studies were proposed and submitted to the Panel for consideration Panel used  framework to identify areas and methodological issues where additional illustrative case studies were needed Those case studies were invited to be brought to Workshop III

Organizational Framework: Dose-Response Methods Presented ARA Workshop II

In-Depth Dose-Response Assessment ARA Workshop II

Workshop Agenda: Day 1 (8:15 am-5:30 pm) Welcome and Introduction: Dr. David Evans, Noblis, and Dose-Response Advisory Committee members Keynote Address: Rita Schoeny, EPA Presentation of Framework & Cross-Cutting NAS Issues: Lynne Haber, TERA Lunch speaker: Bette Meek, University of Ottawa Science Panel Discussion Questions related to MOA Observer Comments Review of New Case Studies

Workshop Agenda: Day 2 (Thursday, May 5) Day 2 (8 am-5:30 pm) Review of New Case Studies (Cont’d) Keynote Talk: Resha Putzrath, U.S Navy Report on Case Study Progress from Workshop II Lunch speaker: James Swenberg, University of North Carolina Science Panel Discussion Questions related to Background & Endogenous Exposure and Background Response Science Panel Discussion of Additional Cross- Cutting NAS Issues

Workshop Agenda: Day 3 (Friday, May 6) Day 3 (8:30 am -noon) Science Panel Discussion Observer Comments/Open Discussion Closing Remarks ARA Workshop II

ACC Center for Advancing Risk Assessment Science & Policy (ARASP) Perspective Group of chemical-specific groups working towards improving risk assessment science and policy, given changing world of toxicology. Accelerate the development, evaluation and use of weight- of-evidence frameworks, MOA analysis, & quantitative uncertainty methods in chemical risk assessments. Support ARA-sponsored workshops to broaden & deepen scientific discussion on dose-response assessment & MOA Contribute case studies / scientific data & analyses and actively participate in the scientific discourse of the ARA project.

TCEQ’s Perspective Commissioner’s and executive management of the Texas Commission on Environmental Quality support these series of workshops Environmental regulations should be meaningful and provide the most benefit to those who need help Good science should lead the way and improve the process

EPA Perspective The case studies being developed by this workshop series will be useful to the Agency as it moves forward in addressing the recommendations presented in Science and Decisions.

Location: Noblis, Falls Church, VA Beyond Science and Decisions: From Problem Formulation to Dose-Response. Workshop III Date: May 4-6th, 2011 Location: Noblis, Falls Church, VA ARA Workshop III