# Presentation: 461048

## Long Term Goal 2 Overview State-of-the-Science Risk Assessment Models, Methods, and Guidance

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**Office of Research and Development**
- National Center for Environmental Assessment

- Long Term Goal 2 Overview State-of-the-Science Risk Assessment Models, Methods, and Guidance

- David Bussard, NCEA-W Division Director
- November 15, 2007

## Presentation Outline

- Relevance and Overarching Goals
- Program Design and Recent Accomplishments
- Broad Charge Questions
- Charge Questions Specific to LTG-2, models, methods, and guidance

## Relevance: What is our Goal?

- Timely, Quality, Chemical Assessments – and LTG-2 Providing Tools, Methods, and Databases Most Needed for Them
- 						PPRTVS

## ...& Quality Risk Assessments Broadly:  Selected Other Inputs 
Primarily Exposure Factors
Broadly-needed
Comparative Advantage 
		to Central ORD Source

- Primarily Exposure Factors
- Broadly-needed
- Comparative Advantage
- 		to Central ORD Source

- Relevance: What is our Goal?

## RelevanceHow Does the Goal Guide Project Selection?

- Priority Assessor Needs			Chemical Assessments
- Science Developments Ready for Use
- Risk Characterization Needs		Other Selected Inputs

## Priority Needs and Program Design

***Review how program matches needs, using recent outputs as examples***

## Priority Needs and Program Design

- Approaches for Assessing Environmental Exposures
- Exposure Factors Handbook (Revisions)
- Child-Specific Exposure Factors Handbook (External Review Draft)
- Guidance on Selecting Age Groups for Monitoring and Assessing Childhood Exposures to Environmental Contaminants (Final Report)
- All-Ages Lead Model (AALM) Version 1.05 (External Review Draft)

**Notes:**
Age-Binning

## Priority Needs and Program Design

- Internal Dose and PBPK Modeling
- RfC Methodology (1992, working to update)
- Approaches for the Application of Physiologically-Based Pharmacokinetic (PBPK) Models and Supporting Data in Risk Assessment (Final Report)
- International Workshop on Uncertainty and Variability in PBPK (2006)

## Priority Needs and Program Design

- Hazard Characterization
- Guidelines for Carcinogen Risk Assessment (Final) and the Children’s Supplemental Guidance
- Summary of the NCEA Colloquium on Current Use and Future Needs of Genomics in Ecological and Human Health Risk Assessment (Final Report)
- Dose-Response Analysis
- Updates of BMD model for analysis of endpoints with continuous data
- Development of CatReg models for analysis of endpoints across multiple domains for toxicity (e.g., functional observational data for neurological function)

## Priority Needs and Program Design

- Risk Characterization [and cross-cutting issues]
- A Framework for Assessing Health Risk of Environmental Exposures to Children (Final Report)
- Aging and Toxic Response: Issues Relevant to Risk Assessment (Final Report)
- Use of Physiologically Based Pharmacokinetic (PBPK) Models to Quantify the Impact of Human Age and Interindividual Differences in Physiology and Biochemistry Pertinent to Risk (Final Report)

## Frequently Downloaded LTG 2 Products in 2007 (Jan-Aug)

## Science Opportunities

- Computational
- Biochemical/Mechanism Detail
- *Omics

## Changing Emphases for Risk Characterizations

- Transparency About Impacts Of Choices Made
- Not Just Upper-end Estimates
- Differing Populations
- In carrying out this section,...The Administrator shall,...specify, to the extent practicable
- (i) **each population** addressed by any estimate of public health effects;
- (ii) **the expected risk or central estimate** of risk for the specific populations;
- (iii) each appropriate **upper-bound or lower-bound** estimate of risk;
- (iv) **each significant uncertainty** identified in the process of the assessment of public health effects and studies that would assist in resolving the uncertainty; ....
- 					[SDWA: ***42*** ***USC*** Sec. 300g-1(b)(3)(B)]

## Susceptible Populations And Sources Of Variability

- Estimation Of Expected Values And Quantifying Uncertainty

## Need to Target Our Efforts

- Areas that Critically Affect Assessments
- New Science Ready for Consideration
- Changing Emphases in Characterization Objectives
- Critical Mass

## Strategies

- Experienced, Expert, Staff and New Post-Docs and Staff  (Tab O)
- Cross-discipline Work Teams (Tab O, Tables 2&3)
- Collaborations With ORD Colleagues and External Experts
- Case Studies
- Forums, Workshops

## Quality

- Teams: Users, Biology, Quantitative Experts
- Internal And External Involvement
- Internal And External Reviews

## Leadership

- Highly significant guidances
- Convening and participating in risk assessment community. (Poster 13)

## Coordination and Communication

- Outreach as Part of Development
- Strong Links to Assessment Users
- Learning from External Groups
- Collaborations with rest of ORD and EPA
- Outreach to Share Final Tools, Methods, Guidances (Tab O)
- Web, Publications, Training
- Planning Other ORD Research

## Examples of ORD Collaborations 

**Identify and define research needs**
- Work with NCER on proposals
- Work with labs to identify priority research needs
**PBPK workgroup and projects with other Labs and Centers**
- Approaches for the Application of Physiologically-Based Pharmacokinetic (PBPK) Models and Supporting Data in Risk Assessment (Final Report)
- Workshops on: Uncertainty in PBPK; and, Good Practices
- Database on physiological parameters
- Collaborative modeling on specific chemicals
**Disinfection By-Products (DBP) Research and Analysis**
- Research coordination and planning
**Staff work on research planning and coordination teams for other MYP**
- As shown by our staff being co-authors on a number of ORD MYPs

*RISK ASSESSMENT:  INTEGRATING SCIENCE INTO DECISION-MAKING*

## Outcome: Success

- The Quality and Usefulness of the LTG-1 and LTG-3 Assessments
- Contribution to Quality and Usefulness of EPA Risk Assessments

## Charge Elements Specific to LTG-2

- Appropriateness
- Topics Often Arise from Assessment Work
- Hard to Do Quality Assessments Without These
- Quality
- Highly-Respected Methods
- Peer Review and Revision
- Use by IRIS, EPA, and Others
- Evidence in LTG-1 Presentations
- Downloads and Users

## Charge Elements Specific to LTG-2

- Do Products Enhance
- Scientific quality and objectivity;
- Characterization of risk and uncertainty; and
- Quantitative analysis of uncertainty?

## Posters

- Organized in roughly similar order to slides on how priorities guided past accomplishments.
- Illustrate some of our recent or current work and directions for the future.

## Posters

***Approaches for Assessing Environmental Exposures***
- Improving Chemical Risk Assessment with **Better Exposure Assessments**
***Internal Dose and PBPK Modeling***
- Chronic **RfC and Exposure-Response Methodologies** in Revision and Under Development
- Advancing the Development, Evaluation, and Use of Physiologically-Based Pharmacokinetic **(PBPK) Models in Risk Assessment**
***Hazard Characterization [and Dose Response]***
- Use of **Mode of Action** Data to Inform Human Health Risk Assessment
**Whole Mixture Methods** for Assessing Health Risks from Exposures to Chemical Mixtures
**Component-Based** Health Risk Assessment **Methods for Chemical Mixtures**

## Posters

***Dose-Response Analysis***
- Use of **Biologically-Based Dose Response Models**
**Dose-Response Modeling** at EPA: Research and Development
***Risk Characterization [and cross-cutting issues]***
- Utilizing **Early Lifestage** Data in Risk Assessment
- Characterization of Environmental Risks to **Older Adults**
- Evaluation of **Uncertainty**, Data Derived **Uncertainty Factors**, and **Variability**
***Other***
- Approaches To Address **Emerging Issues** In Risk Assessment
**Leadership, Collaboration and Promotion** in the Development and Use of Risk Assessment Models, Methods, Databases, and Guidance

## Quantitative Analysis of Uncertainty

- Component Approaches
- Exposure factors handbook
- PBPK for quantitative risk assessment
- Sensitivity of dose-response models
- Consideration of uncertainty is part of how we study any component of risk assessment.
- Integrative Frameworks -- White Papers and Dialogue

## Uncertainty Analysis in Posters

**Poster 1:  Improving Chemical Risk Assessment with Better Exposure Assessments **
- Variability in exposure factors
**Poster 2:  Chronic RfC and Exposure-Response Methodologies in Revision and Under Development**
- Sensitivity to variation in nasal geometry
- Data arrays for transparency about data across studies
**Poster 3: ****	****Advancing the Development, Evaluation, and Use of Physiologically-Based Pharmacokinetic (PBPK) Models in Risk Assessment**
- PBPK inputs and models as source of insight into variation in population and uncertainty in risk estimates
**Posters 4 & 5: Utilizing early lifestage data in risk assessment *****and *****Characterization of environmental risks to older adults**
- Source of variability in population
- Uncertainties when data not available on early-age or older people
**Poster 6:  Use of Mode of Action Data to Inform Human Health Risk Assessment**
- Need to consider multiple MOAs and uncertainty as to alternative moa hypotheses

*RISK ASSESSMENT:  INTEGRATING SCIENCE INTO DECISION-MAKING*

*RISK ASSESSMENT:  INTEGRATING SCIENCE INTO DECISION-MAKING*

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## Uncertainty Analysis in Posters

**Poster 7:****	****Use of Biologically-Based Dose Response Models**
- increasing importance if estimating more than upper-end risk
- sensitivity to unmeasured model inputs and to choice of control explored
**Poster 8:****	****Dose-Response Modeling at EPA: Research and Development**
- PODs that reflect uncertainties
- confidence limits at boundaries for parameters
**Posters 9 & 10:  Whole Mixture Methods for Assessing Health Risks from Exposures to Chemical Mixtures *****and***** Component-Based Health Risk Assessment Methods for Chemical Mixtures**
- goal to reduce uncertainties
- need to also recognize remaining uncertainties
- 	         (mixtures can vary; combination approaches uncertain)
**Poster 11:****	****Evaluation of Uncertainty, Data Derived Uncertainty Factors, and Variability**
**	****   ****-     **white papers, workshops, NAS Futures
- 	   -     monte carlo modeling
- 	   -     analyzing sources of uncertainty, using in risk assessments**	**
**Poster 12:****	****Approaches to Address Emerging Issues in Risk Assessment**
- uncertainties in estimates of relative uncertainty factors
**Poster 13:****	****Leadership, Collaboration and Promotion in the Development and Use of Risk Assessment Models, Methods, Databases, and Guidance**

*RISK ASSESSMENT:  INTEGRATING SCIENCE INTO DECISION-MAKING*

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## 10:15 - 10:45 a.m.	Overview of LTG2

- 10:45 - 12:15 p.m.	Poster Session for LTG2
- 12:15 – 12:30 p.m.	Public Comment
- 12:30 - 1:30 p.m.	Lunch
- 1:30 - 2:00 p.m.		Poster Session Discussion/Questions on LTG2