Toxicology Excellence for Risk Assessment

1. About TERA: a non-profit,501(c)(3) corporation mission to protect public health founded in 1995 with a current technical staff of 12 and several visiting scientists and associates. Complete roughly 50 technical projects per year for government and industry sponsors (strive for 50:50 balance) Focus on – solving risk issues by 1) technology leadership, 2) building bridges and using collaborative processes http://www.tera.org Toxicology Excellence for Risk Assessment

3. TERA Program Areas • Verifiable Estimates for Risk Assessment (developing new risk values) • Peer Review and Peer Consultation (expert input on risk values and methods) • Research Program (developing state-of-the-science methods and guidance in risk assessment • International Toxicity Estimates for Risk (ITER) – comparative database of risk information • StateHELP – pro bono risk support for State and local risk assessors.

4. Recent Pesticide Related Projects • Chlorpyrifos – evaluation and manuscript on cholinesterase vs. developmental neurotoxicity as critical effect for RfD. Presented to Israel Dept. of Health. • Captan reclassification for cancer – peer review on tumor mode of action. Results accepted by EPA OPP as external review. • Chloropicrin – used advanced dose-response modeling to develop acute inhalation exposure limits. Results considered by State of California in setting ambient levels and POD estimate received positive comment from EPA OPP.

5. Other Pesticide Related Projects • EPA Star proposal developing linked PBPK and exposure model for evaluating biomonitoring data – pyrethroids used as case study • Tumor MOA analysis for Telone – led to additional studies by Dow. • Support for pesticide Inert reevaluations. • ACC supported research project used warfarin and parathion to quantfy impact of gene polymorphism on variability in tissue dose. • Ongoing TERA work for EPA on drinking water criteria documents and 6-year reviews based on reproductive and developmental toxicity

6. Alliance for Risk Assessment (ARA) A proposal to provide federal, state, tribal, and private stakeholders with additional… scientifically-based, independently-derived, peer-reviewed, & verifiable risk values & methods for… environmental decision making

7. Alliance for Risk Assessment (ARA) Stakeholder Process Alliance “Menu” Options States, Fed. Agencies, Public Interests, Industry Steering Committee Risk Document Development Initiation of Risk Issue Training and Certification Non-profit Collaborators Hazard Assessment Notification System (HANS) Risk Communication Document Draft Risk Research And Tools Peer Reviews Peer Consult Peer Review Release to Public ITER

8. Key Benefits of the Alliance • Promotes science-based decision making to protect human health • Enhances harmonization and consistency in risk assessments thru an open, transparent, multi-stakeholder approach • Provides user control of own process, while providing parallel process for shared help. • Maintains essential core group of experts that are normally not available within a single agency or state • Shares costs and human resources among multiple stakeholders to increase output

9. ARA Work Flow Steering Committee Role: Provides Advise to Non-Profits on: Mission-related COI Task Priority Membership: (2) Federal Agency (2) State Ag. (1) Tribe (1) NLM (1) TERA (1) Env. NGO (1) Industry (1) Academic Steering Committee Federal Agencies, Industry Funded Projects Hazard Assessment Notification System (HANS) TERA and Non-Profit Collaborators States, Tribes, Env. NGOs Unfunded Project Requests Non-Profits/Collaborators Concurrent Technologies Corp. National Library of Medicine Mitretek TERA ITER

10. ARA Funds Flow ARA Process Federal Agencies Federal Funds Federal Funds Unfunded State Projects 100 Risk Issues per Year by Year 5 Contracts Funded Projects Industry Contracts

11. Why Would Diverse Groups Provide Funding? • The Alliance for Risk Assessment (ARA) mission… • Aligns with many public health goals. • Provides value as a timely resource for technical products with enhanced credibility. • Allows Stakeholder input – e.g., via involvement in Science Steering Committee, as participants in technical panels. • Gives an opportunity for harmonizing risk values and methods – which eases burden for stakeholders that must meet requirements in multiple constituencies. • Over the years nonprofit corporations have demonstrated the concept can work [e.g., peer consultation with Voluntary Children’s Chemical Evaluation Program (VCCEP) of EPA]. • NLM & TERA have success in building ITER; ~200,000 hits per month demonstrates likely value of ARA • Aligns with stated needs of stakeholders – e.g., Environmental Council of States (ECOS) call for harmonized process.

13. NLM’s Toxnet

14. Does Stakeholder Interest Exist? • In exploring the needs for this ARA, TERA has provided briefing and/or received input from many potential stakeholders (over 100 individuals) Including: • 20 States • 2 Tribes • 4 Environmental NGO’s • 30 Industry groups • 6 U.S. Federal Agencies • 4 Countries • Feed back has been positive. Suggestions have led to refinements in the proposed ARA. Nearly all responding contacts have encouraged moving forward. • Diverse groups are beginning to provide funding or suggest projects

15. Does This Effort Duplicate Current Federal Efforts? • This effort does not duplicate ATSDR MRLs, EPA IRIS, FDA ADIs, Health Canada TDIs or RIVM TOCs. • To the contrary, ARA shares resources to avoid duplication because: • It does not replace individual regulatory processes; ARA users tap in as appropriate. • Many risk values/issues will never be worked by federal groups. • Current federal approaches have resource limitations; thus, new chemicals addressed without duplicate effort. • Update of older values can benefit federal groups as one technical input to internal deliberations. • ARA goes beyond risk values/issues – it is also a shared resource for training and data communication.

16. ARA Supports Existing Risk Values • Provides guidance for sources of toxicity information that may be used in performing human health risk assessments • ITER can supplement existing toxicity data • ARA can provide Tier III values EPA OSWER Directive 9285.7-53

17. Why a non-profit? From a government perspective, non-profit status has four benefits: • Independence / Objectivity. We are chartered to operate and act free of commercial or political bias, so we take an objective stance. • Superior Value. All monies go to supporting our mission, allowing us to devote the greatest resources to our work and delivering the highest value for the government dollar. • Usable Results. We are outcome driven and results oriented; our value is measured by the utility of our work—we help sponsoring organizations make a difference. • Kindred Spirit. We share the spirit of public service; we understand the inner workings and detailed tasks that are the key to achieving progress.

18. Mitretek Integration Capability Systems & Technology Enterprise Planning & Analysis • IT architecture systems • Telecommunications network • Information security • Strategic & technology plans • Business engineering & operational analysis • Cost analysis Acquisition Support & Contractor Oversight Environmental, Biological & Chemical Sciences • Environmental impact • Health & environ assessments • Environmental management • Chemical & biological defense • Concept development • Acquisition planning • Requirements, RFP prep www.mitretek.org

19. ARA Next Steps • We are seeking ideas, comments, steering committee nominations, or project requests. • How to contact us: • Soon to be released website at www.allianceforrisk.org • TERA – Andrew Maier; maier@tera.org; 513-542-7475 • Mitretek - Andrew Rak; Andrew.rak@mitretek.org; 703-610-2166