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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
“…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 Collection…other 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:
1. Licensing processes; such as for drug and medicines
2. 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
(EPA’s research program; proposed 2010 budget ~ $580 Million)
3. Large industry effort; pharmaceutical and drug companies
• 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…
PHASE I:
NRC/NAS
Advice
PROBLEM
FORMULATION
AND SCOPING
Risk
Assessment/
Risk
Management
Stakeholder
Involvement
Timeline
PLANNING AND CONDUCT
OF RISK ASSESSMENT
Stage 1: Planning
Synopsis of views
on the problem, a
range of policy
options and
rationales
Includes Risk
Managers
Workshop on
problem and
policy options
PHASE II:
PHASE II:
Integrated Plan:
timeline, key policyrelevant scientific
questions and level
of uncertainty and
variability
analyses
PLANNING AND
CONDUCT
OF RISK ASSESSMENT
Stage 2: Risk
Assessment
Stage 3:
Confirmation of
Utility
From problem formulation to rulemaking
Effects Assessment: concise
evaluation and synthesis of
Risk
most policy-relevant studies for Characterization:
hazard identification and doseNature and
response
Exposure Assessment:
concise, quantitative
assessment of nature and
magnitude exposures
magnitude of risks,
key results and
uncertainties
PHASE III:
RISK MANAGEMENT
Risk Management
Options and
Rulemaking/
Includes Risk
Managers
Workshop on
policy relevant
science
External peer review and public comment
Problem formulation, Scoping,
Planning ~ 6 months
Risk Assessment ~ 2 yrs
External peer review
and public comment
Risk Management ~ 2 yrs
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Health & Environmental
Research Online
EPA’s comprehensive system to identify, compile,
characterize, analyze, synthesize and prioritize
scientific studies.
• Facilitates complete, sustainable and
effective assessment development
• Assures the highest scientific integrity
in data quality.
• Houses citations and study data from • Employs advanced searching and
scientific literature
screening techniques using advanced
algorithms
• Includes studies in EPA’s priority areas
• Utilizes rapid and comprehensive
• Efficient and intelligent information
extraction and synthesis
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
Discovery
Federated Interfaces
Search
Deep Web
Search
Vast repository of
underlying content.
Citations
Visualization
Clustering
Theme Mapping
Classification
HERO
Database
Metadata: scientific discipline,
agents, outcomes, etc.
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Linked Citations
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Assessment Development
Continuous, comprehensive literature
review of peer-reviewed journal
articles in multiple disciplines
Evergreen
Literature
Searches
Study Evaluation
Informative studies
Highly Informative studies
Policy-relevant studies
Additional studies
identified from peer
review, public comment
Additional
studies
Data Extraction
Assessment
HERO Database
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Data Extraction and Analysis
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Decision Support Tools for HighThroughput 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
Exposure
(mg/kgday)
NOAEL
0, 0.05, 0.2,
1, 5,
or 20
90 days in
DW
0.2
1
5
5
5
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, M&F
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
Degenerative nerve changes
(L
Hindlimb foot splay
Decreased body weight Early
mortality after 24 weeks
Other nonneoplastic lesions
Friedman et al., 1995
F344 rat, M&F
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
degenerative nerve changes (L
Decreased body weight (8–
9%)
Early mortality after 60 weeks
Other nonneoplastic lesions
Reference/species
Burek et al., 1980
F344 rat, M&F
LOAEL
(mg/kg-day)
• Large number of animals
• Low throughput
• Expensive
• Time consuming
• Pathology endpoints
• Dose response extrapolations over a wide range
• Application of uncertainty factors
Effect
• 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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Cell Free HTS
Multiplexed TF
Human BioMap
HCS
qNPAs
XMEs
Impedance
Genotoxicity
Chemicals
ToxCast in vitro data (467 assays)
>200,000 dose response experiments
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REACH: An Expected Avalanche of Data
• One million chemicals may
eventually be evaluated.
REACH:
European
Community’s
regulation on
chemicals and
their safe use.
Deals with the
Registration,
Evaluation,
Authorization
and Restriction of
Chemical
Substances.
• Approximately 200,000 chemicals
already have been preregistered for
consideration.
• Dossiers on 40,000 chemicals are
anticipated by 2012.
• REACH also emphasizes replacing
in vivo with in vitro testing.
• Under TSCA Section 8(e), new data
from REACH will come to EPA.
• Additionally, the proposed U.S.
Kid’s Safe Chemicals Act may
model REACH
• Government’s 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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EU’s REACH
Program
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.
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