Transcript EU PRESENTATIONS - Alliance for Risk Assessment

The Evolving Practice of Risk
Assessment – Opportunities for
Collaboration and
Communication
Dr. Bernard Gadagbui
and
Dr. Andrew Maier
February 6, 2007
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
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
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
NAS Risk Assessment Paradigm
(1983)
Risk Assessment
DOSE
RESPONSE
ASSESSMENT
Risk Management
BEST AVAILABLE
TECHNOLOGY
PUBLIC
RESPONSE
HAZARD
IDENTIFICATION
RISK
CHARACTERIZATION
COST
POLITICAL
CONSIDERATIONS
EXPOSURE
ASSESSMENT
ENGINEERING
OPTIONS
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.
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
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)
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
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.
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.
Toxicity Information Sources
Some On-line Databases of Chemical Human Hazard Data
Sources
•
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Toxicology Data Network (TOXNET) (http://toxnet.nlm.nih.gov/)
TSCATS (http://www.syrres.com/esc/tscats.htm)
EPA IRIS (http://epa.gov/iris/)
IPCS INCHEM (http://www.inchem.org/)
NTP (http://ntp-server.niehs.nih.gov/)
ATSDR (http://www.atsdr.cdc.gov/toxpro2.html)
EPA HPV Challenge Program
(http://www.epa.gov/chemrtk/volchall.htm)
• 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.
Toxicity Information Sources
Some On-line Structure Activity Resources
-
Public Domain Tools for conducting similarity of
substructure searches:
• CHEMIDPlus.
http://chem.sis.nlm.nih.gov/chemidplus/cmplxqry.h
tml
• TSCATS (The Toxic Substance Control Act
Test Submission database):
http://esc.syrres.com/efdb/tscats.htm
• AIM (Analog Identification Methodology) (in
development)
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.
Alliance for Risk Assessment
(ARA)
A proposal to provide federal, state, local, tribal,
and private stakeholders with additional…
scientifically-based, independently-derived, peerreviewed, & verifiable risk values & methods for…
environmental decision making
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
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.
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.
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.
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.
ARA Project Areas
• Peer Review
• A peer review process will be established to address the higherlevel, 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.
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
Alliance for Risk Assessment (ARA)
Alliance “Menu” Options
Stakeholder Process
States,
Fed. Agencies,
Public Interests,
Industry
Steering
Committee
Project Area
Risk Document
Development
Initiation of
Risk Issue
Document
Draft
Training and
Certification
Hazard
Notification
System (HNS)
Non-profit
Collaborators
Risk
Communication
Risk Research
And Tools
Peer
Reviews
Peer Consult
Peer Review
Release to
Public
ITER
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
ARA Work Flow
Steering
Committee
Federal Agencies,
Industry
Steering Committee
Role: Provides Advise to
Non-Profits on:
Funded Projects
Mission-related
Hazard
Notification
System (HNS)
COI
Task Priority
Membership:
States,
Tribes,
Env. NGOs
Non-Profit
Collaborators
Unfunded Project
Requests
(2) Federal Agency
(2) State Ag.
(1) Tribe
(1) NLM
(1) TERA
(1) Env. NGO
ITER
(1) Industry
(1) Academic
ARA Funds Flow
•TERA StateHELP
Federal Agencies
Federal Funds
ARA
Process
•ARA Funded Project
Surcharge
•Industry and Federal
Grants
Unfunded State
Projects
100 Risk Issues
per
Year by Year 5
Industry
Contracts
Funded
Projects
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.
ITER Daily Users
Number of Users per Day
450
400
350
NSF Intl & IARC
300
National Library
of Medicine
250
200
150
IRIS, ATSDR &
Health Canada
100
Independent Values
50
RIVM
0
01/3 01/4 02/1 02/2 02/3 02/4 03/1 03/2 03/3 03/4 04/1 04/2 04/3 04/4 05/1 05/2 05/3 05/4 06/1 06/2
Year and Quarter
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
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.
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
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.
www.allianceforrisk.org
Thank You
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 ?