Science to Support Decisions on Environmental Issues of National Importance

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Science to Support Decisions on Environmental
Issues of National Importance
Presentation for the National Academy of Sciences
Board of Research Data and Information Public
Symposium Scientific Data and Evidence Based
Policy and Decision Making September 24, 2009
Peter W. Preuss, Ph.D., Director National Center
for Environmental Assessment Office of Research
and Development U.S. Environmental Protection
Agency
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ensure that federal policies are based on the
best and most unbiased scientific information.
Barack Obama National Academy of Sciences annual
meeting April 27, 2009

• EPA leads the nation's environmental science,
  research, education and assessment efforts.
• The mission of the Environmental Protection
  Agency is to protect human health and the
  environment.
• Since 1970, EPA has been working for a cleaner,
  healthier environment for the American people.
• http//www.epa.gov/epahome/aboutepa.htm

However, in all but one or two program areas, EPA
is asked to accomplish this weighty mission
without a clear mandate or method to obtain the
relevant scientific data and evidence on which to
base a policy or regulatory decision.
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Avenues for Scientific Data and Evidence
Collectionother than EPA

• In some areas, such as drug development and
  certain human diseases, there are established
  pathways to obtain relevant scientific
  information on potential effects
• Licensing processes such as for drug and
  medicines
• Large government research programs, such as the
  National Cancer Institute (NCI) and the National
  Institute of Allergy and Infectious Diseases
  (NIAID)
• NIAID Proposed 2010 Budget 4.8 Billion
• NCI Proposed 2010 budget 5 Billion
• Large industry effort pharmaceutical and drug
  companies

(EPAs research program proposed 2010 budget
580 Million)

• All these pathways for data collection, except in
  the case of pesticides, do not really exist when
  it comes to environmental science for either
  human health issues or ecological issues.
• The situation is worse for scientific data and
  evidence for ecological decision making (e.g.,
  wetlands, fresh and marine water quality)
• But in the absence of adequate data, EPA must
  still act..

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Implementation of Risk Based Decision-Making
Framework
From problem formulation to rulemaking
PHASE II PLANNING AND CONDUCT OF RISK
ASSESSMENT Stage 2 Risk Assessment
PHASE II PLANNING AND CONDUCT OF RISK
ASSESSMENT Stage 1 Planning
PHASE I PROBLEM FORMULATION AND SCOPING
Stage 3 Confirmation of Utility
NRC/NAS Advice
PHASE III RISK MANAGEMENT
Effects Assessment concise evaluation and
synthesis of most policy-relevant studies for
hazard identification and dose-response Exposure
Assessment concise, quantitative assessment of
nature and magnitude exposures
Risk Characterization Nature and magnitude of
risks, key results and uncertainties
Synopsis of views on the problem, a range of
policy options and rationales
Integrated Plan timeline, key policy-relevant
scientific questions and level of uncertainty and
variability analyses
Risk Management Options and Rulemaking/
Risk Assessment/ Risk Management
Includes Risk Managers
Includes Risk Managers
Workshop on problem and policy options
Workshop on policy relevant science
External peer review and public comment
External peer review and public comment
Stakeholder Involvement
Problem formulation, Scoping, Planning 6 months
Risk Assessment 2 yrs
Timeline
Risk Management 2 yrs
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Health Environmental Research Online
EPAs comprehensive system to identify, compile,
characterize, analyze, synthesize and prioritize
scientific studies.

• Facilitates complete, sustainable and effective
  assessment development
• Houses citations and study data from scientific
  literature
• Includes studies in EPAs priority areas
• Efficient and intelligent information extraction
  and synthesis

• Assures the highest scientific integrity in data
  quality.
• Employs advanced searching and screening
  techniques using advanced algorithms
• Utilizes rapid and comprehensive information
  retrieval
• Provides transparency to stakeholders and the
  public

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Literature Search and Screening
Appealing design, relevancy ranking, faceted
navigation
Simultaneous search of multiple databases
Vast repository of underlying content.
Citations
Visualization Clustering Theme Mapping Classificat
ion
HERO Database
Metadata scientific discipline, agents,
outcomes, etc.
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Linked Citations
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Assessment Development
Informative studies are well-designed, properly
implemented, with methods and results thoroughly
described.
Continuous, comprehensive literature review of
peer-reviewed journal articles in multiple
disciplines
Highly Informative studies provide evidence on
mode of action or potential susceptibility to
effects, reduce uncertainty or exposure error, or
offer innovative methods or designs.
Informative studies Highly Informative
studies Policy-relevant studies
Policy-relevant studies may include those
conducted at or near relevant concentrations.
Additional studies identified from peer review,
public comment
Citations from all studies are included in the
database for transparency and accessibility.
HERO Database
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Data Extraction and Analysis
Scientists extract data from policy-relevant
studies to use for cross-study analysis. Figures
such as this Forest Plot show results at a
glance. Links in the online PDF bring the reader
to the full extracted data in the HERO Database.
This easy-to-understand graphic distills
complicated scientific data for use by
policy-makers including the EPA Administrator
and the public.
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Decision Support Tools for High-Throughput Risk
Assessment
PURPOSE To integrate modern computing and
information technology with molecular biology to
improve prioritization of data requirements and
risk assessment of chemicals.
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Current Approach
Table 4-31. Noncancer effects in animals repeatedly exposed to chemical x by the oral route Table 4-31. Noncancer effects in animals repeatedly exposed to chemical x by the oral route Table 4-31. Noncancer effects in animals repeatedly exposed to chemical x by the oral route Table 4-31. Noncancer effects in animals repeatedly exposed to chemical x by the oral route Table 4-31. Noncancer effects in animals repeatedly exposed to chemical x by the oral route Table 4-31. Noncancer effects in animals repeatedly exposed to chemical x by the oral route
Reference/species Exposure (mg/kg-day) NOAEL NOAEL LOAEL Effect
Reference/species Exposure (mg/kg-day) (mg/kg-day) (mg/kg-day) (mg/kg-day) Effect
Burek et al., 1980 F344 rat, MF 0, 0.05, 0.2, 1, 5, or 20 90 days in DW 0.2 1 5 5 5 1 5 20 20 20 1 5 20 20 20 Degenerative nerve changes Degenerative nerve changes Hindlimb foot splay Decreased body weight Atrophy of testes skeletal muscle
Johnson et al., 1986 F344 rat, MF 0, 0.01, 0.1, 0.5, or 2.0 2 years in DW 0.5 2 0.5 0.5 2 2 ND 2 2 ND 2 ND 2 2 ND Degenerative nerve changes (L Hindlimb foot splay Decreased body weight Early mortality after 24 weeks Other nonneoplastic lesions
Friedman et al., 1995 F344 rat, MF 0, 0.1, 0.5, or 2.0 (M) 0, 1.0, or 3.0 (F) 2 years in DW 0.5(M) 1.0(F) 2.0(M) 3.0(F) 2.0(M) 3.0(F) ND ND 2.0(M) 3.0(F) ND ND degenerative nerve changes (L Decreased body weight (89) Early mortality after 60 weeks Other nonneoplastic lesions

• Large number of animals
• Low throughput
• Expensive
• Time consuming
• Pathology endpoints
• Dose response extrapolations over a wide range
• Application of uncertainty factors
• Little focus on mode of action and biology
• Few epidemiology studies

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Future Approach

• In vitro assays anchored by historic in vivo
  bioassays
• Less expensive
• Less time consuming
• At exposure levels of interest hence, limited
  dose response extrapolations
• Predictive tools of human health outcomes rather
  than uncertainty factors
• Primary focus on modes of action and molecular
  biology
• Molecular epidemiology studies

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ToxCast in vitro data (467 assays)
Cell Free HTS Multiplexed TF
Human BioMap HCS
qNPAs XMEs Impedance
Genotoxicity
Chemicals
gt200,000 dose response experiments
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REACH An Expected Avalanche of Data
REACH European Communitys regulation on
chemicals and their safe use. Deals with the
Registration, Evaluation, Authorization and
Restriction of Chemical Substances.

• Governments are ill prepared to utilize the
  volume and complexity of information coming our
  way.
• Work is underway at U.S. EPA to prepare for the
  volume and type of REACH data.

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The Changing Landscape of Human Health Risk
Assessment

• There are tens of thousands of chemicals that are
  untested and lack assessment of potential for
  human toxicity.
• Current toxicology testing methods are too
  expensive, too slow, and can cope with too few
  chemicals.
• Recent advances in biology and computer sciences
  are enabling research that could not have been
  anticipated even 10 years ago.
• Toxicology approaches are evolving away from
  reliance on in vivo testing of laboratory animals
• Current approaches to risk analysis need to be
  significantly modified to deal with more
  chemicals innovative approaches (e.g. Screening
  application, Human health endpoint approach)
• Next Generation (NexGen) risk assessment
  approaches are being discussed that can use the
  new data types and arrays (omics) case study
  approach
• NexGen risk assessments -- Developing a proposed
  strategy to position EPA for the future and
  contribute to meaningful change within the larger
  risk assessment/risk management community.