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Department of Environmental Health

Risk Science Center (RSC)

Dose Response Framework

Overview of Dose-Response Framework

The Alliance for Risk Assessment Dose-Response Framework is a product of the workshop series Beyond Science & Decisions: From Problem Formulation to Dose-Response. Building on the ideas of the National Academy of Sciences' Science & Decisions: Advancing Risk Assessment  (2009), the workshop series brought together 45 organizations seeking to clarify and advance the NAS recommendations.  Specifically, the case studies developed for and presented at the workshop series serve as a compendium of practical, problem-driven approaches for “fit for purpose” risk assessments.  The compendium links methods with specific problem formulations for use by risk managers in a variety of types of organizations (e.g., local, regional and federal governments, private sector).

The framework is currently being restructured.  For access to any of the case studies or additional information about the workshop series or the framework, please contact Lynne Haber.

Listing of Case Studies

Lead – Dose-response relationship for effect on Children’s IQ
Carrington C.D.

  • Risk Assessmentof Exposure to Trihalomethane Drinking Water Disinfection By-Products. 
  • Use of Biomonitoring Equivalents and Biomonitoring Data from NHANES Aylward L.L., Hays S.M., Kirman C.R., Becker RA
  • Risk-Risk Comparison:  Comparative Risk for Use of Perchloroethylene (Perc) or N-propyl-bromide (NPB) in Dry Cleaning Clewell H., Finkel A.
  • BBDR model for respiratory tract carcinogenicity of inhaled formaldehyde Allen B., Clewell H., Conolly R., Haney J., Kester J.
  • Assessment of Low-Dose Dose-Response Relationships (Non-linear or Linear) for Genotoxicity, Focused on Induction of Mutations & Clastogenic Effects Moore M., Pottenger L., Zeiger E., and Zhou T.
  • Implications of Linear Low-Dose Extrapolation from Benchmark Dose for Noncancer Risk Assessment  (noncancer risk) Kroner O., Haber L. Advisor: Dourson M.
  • Framework for Evaluating Alternative Temporal Patterns of Exposure for Risk CharacterizationMaier A., Haber L., Haney J., Kaden D.A., Carrier R., Craft E., and Hertzberg R. Advisor: Dourson, M.
  • Review and application of data fusion methodologies for toxicological dataset analysis to resolve data quality issues in predictive toxicology and contaminated sites risk assessment. Mohapatra A.K., Sadiq R., Zargar A., Islam S., Dyck R.
  • Use of human data in cancer risk assessment of chemicals as illustrated by the case of 1,3-Butadiene.   Albertini R., Sielken Jr. R.L.
  • The Quantitative Human Health Risk Assessment for 1,3-Butadiene Based Upon Ovarian Effects in Rodents Kirman C.R., Grant R.L.
  • Apply AEGL Methodology to Develop Acute Exposure Guideline Levels for Ethylbenzene Grant R., Erraguntla N., Hinz J., Camacho I.A.
  • Deriving Health-Protective Values for Evaluation of Acute Inhalation Exposures for Chemicals with Limited Toxicity Data Using a Tiered Screening Approach  Grant R.L., Phillips T., Ethridge S. Consideration of Human Kinetic Variability (trichloroethylene) Lipscomb J.C., Teuschler L.K., Swartout J., Popken D., Cox T., Kedderis G.L.
  • Multiple modes of action and risk assessment modeling Hertzberg R. Advisor: Dourson M.
  • Application of National Research Council “Silverbook” Methodology for Dose Response Assessment of 2,3,7,8-Tetrachlorodibenzo(p)dioxin. Simon T., Stephens M., Yang Y., Manning R.O., Budinsky R.A. and Rowlands J.C.
  • Estimate Risk Above the RfD Using Uncertainty Factor Distributions (noncancer risk) Spalt E., Kroner O. Advisor: Dourson M.
  • Use of biomarkers in the benchmark dose method Gentry R., Van Landingham C., Hays S., Aylward L. Sustainable Futures Screening Becker E., Ranslow P.
  • Biologically-Informed Empirical Dose Response Modeling:  Using Linked Cause-Effect Functions to Extend the Dose-Response Curve to Lower Doses (Titanium dioxide - TiO2)  Allen B., Maier A., Willis A., Haber L.T.
  • Ethanol Case Study – Evaluating Human Dose-Response of Morbidity and Mortality from Hepatic Disease: Are the Predicted Risks from Low-Dose Linear Extrapolation to Environmentally Relevant Concentrations Biologically Plausible? Becker R., Hays S.
  • Use of Categorical Regression – Risk Above the RfD  (noncancer risk) Danzeisen R., Krewski D., Chambers A., Baker S., Hertzberg R., and Haber L.
  • Development of Screening Tools for the Interpretation of Chemical Biomonitoring Data Richard A. Becker, Sean M. Hays, Steven Robison, Lesa L. Aylward, Christopher R. Kirman
  • Criteria Requirements for Data-Driven Carcinogenicity Mode of Action (MOA) Determinations as Exemplified by Chloroform Chris Borgert, Applied Pharmacology Toxicology Inc.
  • Value of Information: Approach and Case Studies  Eric Ruder, Henry Roman
  • The Human Relevant Potency Threshold: Reducing Uncertainty by Human Calibration of Cumulative Risk Assessments Chris Borgert, Applied Pharmacology Toxicology Inc.
  • Methods for Deriving Inhalation Effect Levels for Comparison to Health-Protective Values  Roberta Grant Endogenous Chemical Risk Assessment: Formaldehyde as a Case Example Robinan Gentry, Tom Starr, Jim Swenberg
  • Hypothesis-Based Weight of Evidence (Naphthalene as an Example) Lorenz Rhomberg, Lisa Bailey
  • Interpretation of 24-hour sampling data. Case Study A. Texas Commission on Environmental Quality Approach Roberta L. Grant; Allison Jenkins; Joseph (Kip) Haney
  • Interpretation of 24-hour sampling data. Case Study B. Ontario Ministry of the Environment (MOE) Approach Denis Jugloff; Julie Schroeder
  • Weight of Evidence Approach for Chemicals with Limited Toxicity Data (silanes and siloxanes) Tiffany Bredfeldt, Jong-Song Lee, Ross Jones, Roberta Grant
  • A systematic assessment methodology for flame retardants (FRs) based on hazard and exposure- the FR framework Smadar Admon, Marc Leifer, Joel Tenney, Tami Weiss-Cohen


Frequently Asked Questions

 How was the ARA Dose-Response Framework created?

The ARA Dose Response Framework is a product of the Beyond Science & Decisions workshop series, a collaboration of over 45 organizations representing government, industry, scientific societies, consultancies, and environmental NGOs. The series built on the ideas presented in the National Academy of Sciences’ Science and Decisions: Advancing Risk Assessment (2009). The framework was developed by panel members and workshop participants as a way of organizing the case studies and methods considered in the workshop series, in order to help identify gaps in methods and to aid risk assessors in identifying useful tools for different problem formulations.  The draft framework was removed by the workshop panel and the DRAC.  The Framework is intended as a tool to help guide the risk assessor in selecting an appropriate dose-response method based on data availability and risk management context, and to help the field of risk assessment identify gaps in methodology. Inclusion of a method or case study in the framework as an illustration of a useful technique does not imply panel acceptance of the chemical-specific outcome.

National Academy of Sciences (2009). Science and Decisions: Advancing Risk Assessment (NAS Final Report).

 How often is the Framework updated?

The Framework is an “evergreen” database, intended to grow and evolve over time to reflect the state of the science.   It is envisioned that it wil be updated twice each year following the Science Panel's review of submitted case studies.

 How can a dose-response method be added to the framework?

All methods included in the ARA Dose-Response Framework are reviewed by an Science Panel for completeness and utility.  The panel review considered whether the case studies were scientifically defensible, useful relative to the problem formulation, practical, and made biological sense.  The panelists were also asked to identify areas where case studies may need additional work.  The panel focused on the case study methods, and did not review key decision points or final risk assessment results for the case studies that involved specific chemical assessments. 

Panel review of submitted case studies is expected to occur twice each year.

If you would like to suggest a method for inclusion in the framework, please contact Lynne Haber.

 What was the Alliance for Risk Assessment?

The Alliance for Risk Assessment (ARA) was a collaboration of organizations that fosters the development of technical chemical risk assessment products and services, through a team effort of specialists and organizations dedicated to protecting public health by improving the process and efficiency of risk assessment, and to increasing the capacity for developing risk values to meet growing demand.  The ARA coordinated with Federal and State Agencies whenever possible, to ensure the best use of available resources, and to avoid duplication of effort. 

 What is problem formulation?

In risk assessment, problem formulation is the phase in which the risk managers’ charge to the assessors is converted into an actionable plan for performing the assessment (EPA 1998; Suter 2007).

EPA (U.S. Environmental Protection Agency). 1998. Guidelines for Ecological Risk Assessment. EPA/630/R- 95/002F. Risk Assessment Forum, U.S. Environmental Protection Agency, Washington, DC. April 1998 [online]. Available: 
Suter, G.W. 2007. Ecological Risk Assessment, 2nd Ed. Boca Raton, FL: CRC Press.