1. Dr. Bernard Gadagbui and Dr. Andrew Maier February 6, 2007
The Evolving Practice of Risk Assessment – Opportunities for Collaboration and Communication
Dr. Bernard Gadagbui
and
Dr. Andrew Maier
February 6, 2007

2. Objectives of Presentation
Briefly describe:
Chemical risk assessment
How EPA quantifies risk posed by chemicals
Trends in risk assessment
The growing need for information sharing
Introduction of Alliance for Risk Assessment as a resource for information exchange

3. Risk Assessment Risk is defined as…
“the possibility of loss or injury; someone or something that creates or suggests a hazard; and the degree of probability of such loss”
“the probability of an adverse outcome”
Casarett & Doull, 2001

4. Risk Assessment Human Health Risk Assessment is…
The scientific process of evaluating the toxic properties of a chemical and the conditions of human exposure to it, in order to both ascertain the likelihood that exposed humans will be adversely affected, and to characterize the nature of the effects they may experience.
Human health risk assessors evaluate issues such as:
the quality of community air and water due to emissions,
the safety of food and consumer products, and
the need to clean-up contaminated sites

5. NAS Risk Assessment Paradigm (1983)
Risk Management
HAZARD
IDENTIFICATION
DOSE RESPONSE
ASSESSMENT
EXPOSURE
RISK
CHARACTERIZATION
BEST AVAILABLE
TECHNOLOGY
ENGINEERING
OPTIONS
PUBLIC RESPONSE
POLITICAL
CONSIDERATIONS
COST

6. Trends in Risk Assessment
Past:
Analysis efforts focused on selected high profile chemicals.
Heavy reliance on default assumptions
Humans are equally or more sensitive than test animals
Humans are highly variable in their sensitivity
Effects observed in high dose animal studies are relevant to effects that might occur in humans exposed to low doses
Ambient exposure related empirically to disease without regard to the assessment of biological modes of action.
Overall, the use of default assumptions resulted in environmental risk assessments with significant uncertainty.

7. Trends in Risk Assessment
Present:
Increasing emphasis on hazard characterization and screening assessments for large numbers of chemicals
Exploration of mechanisms/modes of action at cellular and molecular levels
Increasing use of data to replace or inform default assumptions
Use of weight of evidence (WOE) approach
WOE characterized by use of “totality of the evidence” in making risk assessment decisions
The risk assessment process encompasses all available toxicological data and scientific evidence on the plausible toxicities of a chemical or chemicals

8. Trends in Risk Assessment
Future:
WOE has opened door for innovative solutions in risk assessment and toxicology
Ability to employ innovative solutions has been driven by
Improved biology understanding (understanding of the mode of action or MOA)
Increased sophistication and validation of alternative study designs and consideration of study design (e.g., gene knock-outs)
Improved quantitative tools (including biomathematical modeling, data mining and collection platforms (toxicogenomics) and predictive toxicology and Quantitative Structure Activity Relationships, QSARs)

9. Evolving Risk Assessment
Triggered by…
Control technology better able to reduce gross contamination, focusing effort on smaller releases
New technologies for detecting lower amounts of pollutants is increasing knowledge of chemicals in the environment
Significant advancement in scientific knowledge
Advances in basic biology (molecular and cellular biology), chemistry (computational chemistry), and mathematics (better statistical and dose-response tools)
More subtle effects as opposed to gross effects

10. Evolving Risk Assessment
Triggered by….
Need to estimate long-term effects from exposure to environmentally relevant concentrations – i.e. effects of exposure not immediately known.
Recognition of need to conduct risk assessment on broader range of chemical inventory as opposed to individual chemicals
European Union REACH
Health Canada Domestic Substances List (DSL)
U.S. EPA HPV
All these factors have increased public awareness regarding the environmental decision making, including risk assessment.

11. Current Risk Assessment Challenges
Extrapolation of toxicology data
extrapolating results not only from animal toxicity studies,
extrapolating from the very high doses usually used in animal experiments to the very low doses that are characteristic of human exposure.
Lack of adequate information
Of the hundreds of thousands of chemicals in commerce – publicly available information is limited to only a few thousand – and in many cases the information is not complete.
These issues generate uncertainty in conducting risk assessments.

12. Toxicity Information Sources
Some On-line Databases of Chemical Human Hazard Data Sources
Toxicology Data Network (TOXNET) (
TSCATS (
EPA IRIS (
IPCS INCHEM (
NTP (
ATSDR (
EPA HPV Challenge Program (
RTECS (Registry of Toxic Effects of Chemical Substances) CDC/NIOSH
EINECS (European INventory of Existing Commercial Chemical Substances Information System)
IUCLID (International Uniform Chemical Information Database) - OECD
RAIS (Risk Assessment Information System) (DOE)
Regional and CA EPA
List serves e.g., Risk Anal and mailing lists
Societies and organizations – MSWG, ECOS, SOT, local chapters, etc.

13. Toxicity Information Sources
Some On-line Structure Activity Resources
Public Domain Tools for conducting similarity of substructure searches:
CHEMIDPlus.
TSCATS (The Toxic Substance Control Act Test Submission database):
AIM (Analog Identification Methodology) (in development)

15. The Need for Information Sharing
Nearly all risk assessment folks now adopt the NAS risk assessment/risk management paradigm for their daily risk activity.
ATSDR, EPA, FDA, Health Canada, RIVM, and other federal groups can likely address their workloads, but cannot be expected to address all of the needed work for states or for private entities.
A venue for governmental, industrial, environmental, and non-profit organizations to collaborate to produce the high quality risk assessment science.

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

17. ARA
A collaboration of organizations that fosters the development of technical chemical risk assessment products and services, through a collaborative effort of specialists and organizations dedicated to protecting public health
The ARA will coordinate with Federal and Sate Agencies whenever possible, to ensure the best use of available resources

18. ARA Tools Hazard Notification System (HNS)
Will be a National Library of Medicine (NLM), web-based system for coordinating work on chemical risk value and methodology documents that are under development or revision
Will provide a platform for notification of human health risk assessment projects in progress or completed projects that have either not been peer reviewed and/or are ineligible for inclusion on the International Toxicity Estimates for Risk (ITER) database of chronic human health risk data
HNS will also identify risk assessment data gaps and will contain non-chemical information related to human health risk assessment, such as training modules, white papers and risk documents.
Groups working on a chemical or issue of interest will be identified and this will allow stakeholders an opportunity to provide input on ongoing assessments or develop collaborations with document authors.
Will be linked with the ITER database and will be fully searchable against other databases in the TOXNET system.

19. ARA Tools International Toxicity Estimates for Risk Database (ITER)
Free internet database of human health risk values and cancer classifications from a variety of national and international organizations, as well as independent groups
Currently contains risk values for more than 600 chemicals, and is part of the National Library of Medicine’s TOXNET compilation of databases
Only database that presents risk data in a tabular format for easy comparison
Risk values or documents developed under this alliance will be published on ITER after appropriate peer review and approval of the risk values/documents.
This will ensure that new credible risk values developed by both State regulatory agencies and independent groups are widely available to interested parties. 
In addition, peer reviewed risk values already developed by State agencies and independent groups can be uploaded to ITER to foster data sharing. 
The inclusion of individual state’s risk assessment values on ITER would facilitate sharing of information between state and/or local agencies.  

22. ARA Project Areas Risk Issues Document Development for Contaminants
Need for new risk assessment issues documents will be identified by reviewing existing assessments (including coordination through HNS), sharing internal priorities among funding partners and State groups, and evaluating requests made by interested parties.  
For assessments not currently under development, non-profit risk assessment consultancies and academic centers could author such documents for use by the broader risk assessment community. 
Assessments will be conducted according to generally-accepted state-of-the science methods
Newly developed risk assessment values will be posted on ITER after appropriate peer review and acceptance of proposed values. 

23. ARA Project Areas Peer Consultation
conducted by an expert panel comprised of a core group of highly experienced risk assessment scientists from various organizations
Specific experts will address data interpretation issues and provide scientific judgments during document development. 
Individuals from State, academia, public interest groups, and industry. 
The core group will develop and apply a consistent approach to addressing issues encountered in the development of risk values. 
The purpose of this group is to ensure that the documentation meets basic requirements, to apply a consistent approach to addressing generic issues, and to identify key chemical-specific issues that would be useful to highlight during the next step of peer review. 
After the peer consultation, the document authors will revise the document, which can then be submitted for peer review.

24. ARA Project Areas Peer Review
A peer review process will be established to address the higher-level, chemical-specific issues that are part of the assessment, and to reach a consensus position on the appropriate risk values or interpretations. 
The peer review panel consists of ad hoc members convened to address issues specific to the chemical or issue at hand, and would include chemical-specific experts, and experts on issues key to the specific assessment.  

25. ARA Project Areas Training
Develop a mechanism for risk assessment training
Formal training courses and “hands-on” experiences. 
Formal training courses would be conducted for state, provincial, tribal, funding partners, and other interested risk assessors on a variety of topics

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

27. Key Benefits of the Alliance
Promotes science-based decision making to protect human health
Enhances harmonization and consistent use of innovative solutions 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

28. ARA Work Flow Steering Committee Federal Agencies, Industry Hazard
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
Funded Projects
Hazard
Notification
System (HNS)
Non-Profit
Collaborators
States,
Tribes,
Env. NGOs
Unfunded Project Requests
ITER

29. ARA Funds Flow ARA Process Federal Agencies Federal Funds
TERA StateHELP
ARA Funded Project Surcharge
Industry and Federal Grants
Federal Agencies
Federal Funds
Unfunded State Projects
100 Risk Issues
per
Year by Year 5
Contracts
Funded
Projects
Industry
Contracts

30. 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.

32. 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:
30 States
4 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

33. Does This Effort Duplicate Current Federal Efforts?
This effort does not duplicate ATSDR MRLs, EPA IRIS RfDs/RfCs, 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.

34. 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

35. Tiers of Toxicity Data
The guidance (2003) sets forth three tiers of toxicity data for human health risk assessments:
Tier I – IRIS values
Tier II – other EPA provisional values
Tier III – Other scientifically valid and peer review values
Tier II values are only developed for sites on the Superfund National Priorities List (NPL). Therefore, sites not on the NPL with specific chemical issues must use Tier III if chemical toxicity data is not in IRIS.

37. Thank You

38. Discussion Topics
What information sharing resources does your group use for sharing information of innovation in risk assessment?
Are the current information exchange resources adequate?
What ideas/suggestions do you have for increased information sharing ?