Connecting Innovations in Biological, Exposure and Risk Sciences: Better Information for Better Decisions

1. Connecting Innovations in Biological, Exposure and Risk Sciences: Better Information for Better Decisions Charleston Place Hotel United States June 16 - 17, 2009

2. Providethe science foundation that can enable society and the industry to make fair and responsible product stewardship and regulatory decisions concerning the production, marketing, and use of our products. The Goal

3. Global Positioning • The LRI is a global program, under ICCA • Significant presence in North America, Europe, and Japan

4. From Data to Decisions: Informing Regulatory Policy

5. LRI OutreachICCA-LRI Workshops • Since 2005, LRI has held 5 international workshops • In 2009, Nearly 100 participants from 15 countries: ~30% from international governments ~40% from academia and NGOs ~30% from industry • Provided a dynamic forum for discussing how new toxicity testing technologies can be applied to regulatory decision-making

6. Previous Workshop Outcomes • Forged significant research collaborations • Placed a spotlight on the need for responsible communication of complex scientific information • Kept industry’s commitment to science and research in the public eye • Mobilized industry’s efforts to lead innovations in risk assessment

7. 2009 Workshop Layout • Co-chaired by Elaine Cohen Hubal and Dick Phillips (ExxonMobil) • 3 Plenary Session • 3 Breakout Sessions • Advanced Technologies • Exposure • Communication • Poster Sessions

8. Breakout Sessions • Advanced technologies – How can the data from the new technologies and highthroughput assays for genes, proteins, and metabolism be effectively interpreted for risk assessments of chemicals? • Exposure – What innovations in exposure science are needed to better characterize biologically relevant exposures to chemicals and to understand their implications for human health risks? • Communication – Which frameworks can best communicate new scientific information and research outcomes to all stakeholders throughout the research and decision-making processes?

9. Cross-Cutting Theme • A cross-cutting theme for all of the breakout sessions was increased understanding of genetic influences and gene-environmental interactions regarding chemical exposures with a focus on improved risk assessments for susceptible populations, including children.

10. Exposure Sciences Breakout SessionReport-Back

11. Discussion Focus • Exposure assessment has lagged behind toxicity testing • Several (14) presentations on disparate efforts in exposure assessment • Focus • Innovative tools to characterize biologically-relevant exposures and their implications for human health risks. • Cross-cutting theme - Understanding genetic influences and gene-environment interactions as essential elements for improving risk assessments for susceptible populations. • Interpretation of biomonitoring data as a component of characterizing exposures • Panel - Identify what you see as significant research questions and gaps for advancing exposure science and for developing biologically-relevant exposure to inform toxicity testing

12. Day I Presentations • Multimedia modeling of environmental exposure to toxics: From world scale to cm in the body! • Oliver Jolliet, University of Michigan • Targeting exposure research to improve decision-making • Ruthann Rudel, Silent Spring Institute • Extrapolation modeling and computational tools • Louise Ryan, CSIRO Mathematical & Informational Sciences • Understanding the impact of prenatal arsenic exposure through transcriptomics • Rebecca Fry, University of North Carolina – Chapel Hill • Systems biology and the mechanistic indicators of childhood asthma • Stephen Edwards, U.S. Environmental Protection Agency • Predictive exposure science, environmental bioinformatics, and computational toxicology • William Welsh, University of Medicine & Dentistry of New Jersey

13. Day II Presentations PBPK modeling and interpretation of biomonitoring data – Estimation of chemical concentrations in human bodies from their doses for animal studies Hiroshi Yamazaki, Showa Pharmaceutical University Exposure and EPA’s National Exposure Research Laboratory Peter Egeghy, U.S. Environmental Protection Agency Predicting biologically relevant exposures Justin Teeguarden, Pacific National Laboratories Dose reconstruction and extrapolation modeling Russell Thomas, The Hamner Institutes for Health Sciences Consideration of “dose” in evaluation of ToxCast™ data: Use of biomonitoring and pharmacokinetic data Lesa Aylward, Summit Toxicology

14. Some Key General Observations • Biologically-relevant exposures need to be incorporated into real world risk evaluations – validation of premise • Exposure assessment is a trans-disciplinary effort • Exposure (risk) assessments are multi-functional • Environmental contamination • Consumer Products • Indoor Air • Covers both human and ecological receptors • Multi-disciplinary team effort needed for success • Breadth of issues • Depth of knowledge needed • Exposure should be factored into risk assessment (toxicity testing) prior to health effects evaluation • A tiered exposure screening approach

15. Some Key Tools …. • Cumulative/integrated assessments will be (is) new norm – Tools to understand/evaluate the Source-pathway-receptor-dose …effect continuum are being developed widely • Multi-stressors; multi-source …Resource intensive • Leverage activities • Only as complex as it needs to be (tiered screening models) • Statistical tools are available to help optimizing data collection – “do not have to measure everyone perfectly” • Caveat: be mindful of the biological/exposure basis for the measurements

16. More Key Tools …. • Genetic biomarkers of exposure now measurable – what does it mean in terms of disease state • PBPK models/tools have more than promise – still data intensive but becoming more widely used/available • informative for interpreting biomonitoring data • Useful input to interpreting high throughput toxicity testing

17. Some Other Observations • Understanding mechanism of action useful in prioritizing testing • Substitution decisions should be properly framed taking into account mechanisms • Mixtures important • Use re-reconstruction, e.g., currently banned chemicals that are still prevalent

18. Panel Discussion Paul Price, The Dow Chemical Company Modeling cumulative exposures using person-oriented modeling Matti Jantunen, National Institute for Health and Welfare, Department of Environmental Health, Finland Exposure is more than just a number Linda Sheldon, U.S. Environmental Protection Agency

19. Topic for Discussion Identify what you see as significant research questions and gaps for advancing exposure science and for developing biologically-relevant exposure to inform toxicity testing

20. Price - Summary • Cumulative risk - new norm • Multi-stressors; multi-source • Start with people rather than source • Multi-people.. people-oriented models (POM) • Nested loop model.. Probabilistic • Detailed oriented .. • Need to include tiered screening approach

21. Sheldon - Summary • Using exposure science for better decision • Exposure (need improved definition): • Source to dose • Not only assessment; decisions • Right decisions … effective? • Have we improved health; good alternates? • Trans-disciplinary science • Toxicity in 21st Century • 4 areas of focus of new Administration – exposure assessment important in all

22. Jantunen - Summary • Exposure is more than just a number • Many impact pathways link the source to health outcomes RISK? – EpidemiologyHOW? – ToxicologyWHO, WHERE & WHEN (HOW MUCH? – ExposureWHAT CAN WE DO? – Exposure

23. Recommendations • Trans-disciplinary efforts are needed • Choosing materials to study • Exposure information important in determining what toxicological studies are performed • Focus on products and uses going forward • Screening assessment are appropriate but assessments should be as quantitative as possible • Screening rules are needed

24. Detailed research is still needed in many areas of exposure assessment • However, real world exposure evaluations can(/should) proceed with broad strokes.