With improvements in our biological understating, computational power, and an ever-changing regulatory landscape, new methods for evaluating human health impact and risk are emerging. Since 2010, the Beyond Science & Decisions workshop series has provided a venue for testing, vetting, and improving novel risk assessment methods. With the collaboration of over 55 organizations representing government, industry, scientific societies, consultancies, and environmental NGOs, the series has now reviewed over 30 case studies illustrating such methods. The ARA Dose Response Framework includes these case studies and links to key guidance documents on a range of risk assessment issues. It was developed by panel members and workshop participants as a way to categorize and identify gaps in available methods, and to aid risk assessors in identifying useful tools for different problem formulations. It is intended as a tool to help guide the risk assessor in selecting an appropriate method(s) for addressing different issues related to hazard characterization and dose-response assessment, and to help the field of risk assessment identify gaps in methodology. This symposium will highlight several methods that have been presented as part of the workshop series, and then provide an interactive demonstration of the Dose Response Framework and how these methods fit within the framework. The session will then open for audience discussion on enhancements to the Framework.

1. ARA DOSE RESPONSE FRAMEWORK
Oliver Kroner, TERA 1

2. Beyond Science & Decisions
Workshop Objectives
• Build off the NAS (2009)
report
– Develop practical
guidance for use by risk
managers at a variety of
levels
– Risk assessment techniques
applicable to specific
problem formulations.
• Implement a multi-
stakeholder approach to
share information, ideas,
and techniques
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3. Collaborators
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55+ sponsors and collaborators:
• 12 government agencies
• 19 industry groups
• 7 scientific societies
• 9 non-profit orgs/consortia
• 8 consulting groups

4. Standing Panel
• Annie Jarabek, U.S. EPA NCEA
• Richard Beauchamp, Texas Dept State Health Services
• James S. Bus, Exponent
• Mike Dourson, TERA
• R. Jeffrey Lewis, ExxonMobil Biomedical Sciences, Inc.
• Bette Meek, McLaughlin Centre for Population Health Risk
• Assessment, University of Ottawa (Chairperson)
• Greg Paoli, Risk Sciences International (NAS 2009 Panel)
• Alan Stern, New Jersey Dept of Environmental Protection
• Ad hoc: Moiz Mumtaz, Agency for Toxic Substances and
Disease Registry (ATSDR)
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ARA Dose Response Framework

5. Beyond Science & Decisions
• 8 Workshops over 4 years
• Over 40 Case Studies illustrating state-of-the-
science risk methods
– Problem Formulation + Applications
– Data Requirements
– Strengths and Weaknesses
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ARA Dose Response Framework

6. Recognized Need
• Panel requested a “map” of the case studies
– Chart what has been covered, where we have
gaps
• Share with the risk assessment community
– Identify target audience and purpose of the case
studies, and format case studies to be useful for
real world application
• Develop a library of methods
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ARA Dose Response Framework

7. Dose Response Framework (beta)
www.chemicalriskassessment.org
• Audience:
 Risk assessors seeking information on risk methods
• Purpose:
 One-stop-shop for risk methods
 To catalogue, organize, and highlight key aspects of
risk methods
 To demonstrate real world application of the methods
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ARA Dose Response Framework

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9. ARA Workshop IV 9

10. ARA Workshop IV 10

11. ARA Workshop IV 11

12. ARA Workshop IV 12

13. ARA Workshop IV 13

14. ARA Workshop IV 14

15. ARA Workshop IV 15

16. ARA Workshop IV 16

17. ARA Workshop IV 17

18. ARA Workshop IV 18

19. How often is the Framework
updated?
• The Framework is an “evergreen” database,
intended to grow and evolve over time to
reflect the state of the science. It is
envisioned that it will be updated twice each
year following the Science Panel's review of
submitted case studies.
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ARA Dose Response Framework

20. Accomplishments to Date
• >40 case studies catalogued
• Open access manuscript:
– Meek et al. 2013. A Framework for Fit-for-Purpose
Dose Response Assessment. Regul. Toxicol.
Pharmacol. 66(2):234-40. Doi:
10.1016/j.yrtph.2013.03.012
• On NLM’s Enviro-Health Links
http://sis.nlm.nih.gov/enviro/toxweblinks.html
(see Associations)
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ARA Dose Response Framework

21. Next Steps
• Beyond Science & Decisions Workshop 9 –
Spring 2015
http://allianceforrisk.org/ARA_Dose-Response.htm
• Additional methods being added
• Seeking case studies for Panel review
• Seeking user feedback
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ARA Dose Response Framework

22. Clarifying Questions?
Oliver Kroner
TERA
kroner@tera.org
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ARA Dose Response Framework
Acknowledgments:
Dr. Lynne Haber
TERA

23. Questions
1. What features (e.g., advanced search methods)
are missing or could be enhanced?
2. Are additional changes needed to make it easier
to search for methods to address specific
issues/problems? If so, what?
3. The site was designed without emphasis on the
chemicals featured in the various case studies.
Would it be useful to allow users to sort and
filter methods by chemical for identifying
chemical specific information?
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ARA Dose Response Framework

24. Panel Feedback
• Strengthening the emphasis on problem
formulation/fit-for-purpose risk assessment,
which could potentially be done using a
“schematic,” or increasing the focus on
problem formulation on the case study pages
• Panelists asked about the possibility of
creating an instructional video demonstrating
the purpose of the site and how to use it
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ARA Dose Response Framework

25. Panel Recommendations
• Possible rubrics may include:
– Method’s level of acceptance (e.g., new
experimental method, well-established)
– Human-relevance
– Extrapolation assumptions
• Increased inclusion/emphasis on exposure
methods
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ARA Dose Response Framework

26. Panel Recommendations
• Offering an inventory of tools available to risk
assessors (e.g, Benchmark Dose Software),
with links and tutorials as feasible.
• Offering abstracts of key references cited, or
links to where the reference can be found, as
done by U.S. EPA’s HERO Database.
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