The Evolving Practice of Risk Assessment

1
The Evolving Practice of Risk Assessment
Opportunities for Collaboration and Communication

• Dr. Bernard Gadagbui
• and
• Dr. Andrew Maier
• February 6, 2007

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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

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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
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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

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NAS Risk Assessment Paradigm (1983)
Risk Management
Risk Assessment
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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.

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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

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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)

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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

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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.

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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.

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Toxicity Information Sources

• Some On-line Databases of Chemical Human Hazard
  Data Sources
• 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/chem
  rtk/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.

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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/chemidplu
  s/cmplxqry.html
• TSCATS (The Toxic Substance Control Act Test
  Submission database) http//esc.syrres.com/efdb/t
  scats.htm
• AIM (Analog Identification Methodology) (in
  development)

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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.

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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

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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

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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.

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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
  Medicines 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 states risk
  assessment values on ITER would facilitate
  sharing of information between state and/or local
  agencies.  

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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. 

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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.

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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.  

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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

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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
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
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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

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

• 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
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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 Childrens 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.

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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 NGOs
• 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

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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.

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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
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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.

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www.allianceforrisk.org
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Thank You
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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 ?