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Extrapolation from individuals to populations


The focus of this task is to develop and deliver models for translating wildlife toxicity test data into a currency useful for population-level risk assessments by estimating the magnitude of change in demographic parameters (i.e., survival and fecundity rates) resulting from specific chemical exposure scenarios. Toxicity translator models integrate toxicity test endpoints with information on life history characteristics of a species of concern and the timing of chemical exposure during its breeding season. While it is important that toxicity translator models are parameterized using data from existing toxicity tests, there are new or modified toxicity tests currently being evaluated for inclusion in the ecological risk assessment process. An experimental portion of this task will explore how improvements in the experimental design of fish toxicity tests and incorporation of new endpoints increase understanding of Adverse Outcome Pathways (AOP) and improve the ability of toxicity translator models to quantify effects on demographic parameters.

Rationale and Research Approach:

The Office of Pesticide Programs (OPP) has made a priority of improving their ecological risk assessment process to better quantify the probability and magnitude of risks to populations of species of concern. While the existing battery of laboratory toxicity tests provides a suite of test endpoints reflecting specific toxicological responses, none of the endpoints is in the same currency as the demographic parameters (i.e., annual survival and fecundity rates) needed for population-level assessments. Modeling approaches are needed to integrate available toxicity data with information on species life history and the timing of potential chemical exposure in model simulations to estimate the change in survival and/or fecundity rates resulting from defined exposure scenarios.

In the AOP framework, toxicity translator models provide the tools necessary to move from the individual level to the population level by providing population modelers with the data needed on changes to demographic parameters. These toxicity translator models also provide information on which species (or life history characteristics) are at greatest risk from a specific exposure scenario or what exposure scenarios have the greatest impacts on a species of concern. Toxicity translator models would be produced for the vertebrate taxonomic groups currently evaluated in ecological risk assessments--initially fish and birds, though OPP is interested in extending concepts to mammals and amphibians--along with supporting user’s manuals and technical support manuals. The development of toxicity translators requires integration of work on chemical toxicity testing and exposure assessment with ecological systems modeling. By improving the quality of ecological risk assessments to more clearly describe the potential risks to free-ranging populations, toxicity translators are designed to provide risk managers with tools for assessing how a specific chemical-use scenario affects the population sustainability of species of concern. Models would be designed to use data currently available to OCSPP risk assessors and other program offices, and would be flexible enough to incorporate data from new toxicity tests and assays developed through the CSS research program as appropriate.

Along with model development, experimental research will continue to improve the design of laboratory toxicity tests and develop new sub-organismal endpoints that will increase our ability to identify adverse effects and be instrumental in our understanding of AOPs. Small fish are especially useful for developing AOPs for vertebrate reproduction due to the ability to rigorously characterize exposure in laboratory tests and the short reproductive development times. Furthermore, measurements at lower-levels of biological organization, from molecular to pathology effects, are easily incorporated into the test protocols. Growth and reproductive outcomes such as fecundity and fertility are the primary apical endpoints of the full life-cycle fish tests. Linking effects measured at lower-levels of organization such as gene expression profiles and histopathology with reproductive outcomes provides insight into important adverse outcomes at the individual level. Additionally, these apical outcomes at the individual level, can inform toxicity translator modules for important population-level risk assessment models.

Ultimately this research will provide a better understanding of AOPs of vertebrate reproduction. This understanding will help inform the development of better test strategies and extrapolation models. Outputs of this task will be integrated into the wildlife population modeling within CSS Systems Models project 2.4.

MED Scientists:

Frank Whiteman
Richard Bennett
Matthew Etterson
Rodney Johnson
Dean Hammermeister
Douglas Lothenbach
Sigmund Degitz
Kevin Flynn


Bennett, R.S. and M.A. Etterson. 2014. Avian life history profiles for use in the Markov chain nest productivity model (MCnest). EPA Report, EPA/600/R-14/009.

Bennett, R.S.  and M.A. Etterson. 2013. Model and User’s manual for basic version of MCnest Markov chain nest productivity model, online only: http://med.dul.epa.gov/Prods_Pubs/mcnest.htm. EPA Report, EPA/600/R-13/034.

Bennett, R.S.  and M.A. Etterson. 2013. Technical manual for Basic Version of the Markov chain nest productivity model (MCnest), online only: http://med.dul.epa.gov/Prods_Pubs/mcnest.htm. EPA Report, EPA/600/R-13/033.

Bennett, R.S and M.A. Etterson. 2013. On selecting surrogate endpoints for estimating pesticide effects on avian reproductive success. Integrated Environmental Assessment and Management 9:600-609.

Etterson, M.A. and R.S. Bennett. 2013. Quantifying the effects of pesticide exposure on annual reproductive success of birds. Integrated Environmental Assessment and Management 9:590-599.

Flynn, K., J. Swintek, and R. Johnson. 2013. Use of gene expression data to determine effects on gonad phenotype in Japanese medaka after exposure to trenbolone or estradiol. Environmental Toxicology and Chemistry 32:1344-1353.

Johnson, R., S. Degitz, K. Flynn, D. Lothenbach, D. Hammermeister, F. Whiteman, J. Korte, J. Haselman, and P. Kosian. 2013. EDSP Tier 2 test (T2T) guidances and protocols are delivered, including web-based guidance for diagnosing and scoring, and evaluating EDC-induced pathology in fish and amphibian. EPA Integrated Summary Report, https://www.epa.gov/scipoly/sap/meetings/2013/062513meeting.html#materials.

Etterson, M.A., S.N. Ellis-Felege, D. Evers, G. Gauthier, J.A. Gryzbowski, B.J. Mattsson, L.R. Nagy, B.J. Olsen, C.M. Pease, M. Post van der Burg, and A. Potvien. 2011. Modeling fecundity in birds: Conceptual overview, current models, and considerations for future developments. Ecological Modelling 222:2178-2190.

Larocque, G.R., D. Mailly, T.-X. Yue, M. Anand, C. Peng, C. Kazanci, M.A. Etterson, P. Goethals, S. Jorgensen,
J. Schramski, E. McIntire, D. Marceau, B. Chen, G. Chen, Z. Yang, B. Novotna, N. Luckai, J. Bhatti, J. Liu, A. Munson, A. Gordon, and J. Ascough Jr. 2011. Common challenges for ecological modelling: Synthesis of facilitated discussions held at the symposia organized for the 2009 conference of the International Society for Ecological Modelling in Quebec City, QC, Canada , (October 6-9, 2009). Ecological Modelling 222:2456-2468.

Flynn, K., M. Haasch, D.S. Shadwick, and R. Johnson. 2010. Real-time PCR-based prediction of gonad phenotype in medaka. Ecotoxicology and Environmental Safety 73:589-594.

Etterson, M.A., R.S. Bennett, E.L. Kershner, and J.W. Walk. 2009. Markov chain estimation of avian seasonal fecundity. Ecological Applications 19:622-630.

Expected Products:




Sep 30, 2013 Develop avian toxicity translator model for extrapolation from individual to population level effects (basic version, MCnest) including users manual and technical support manual. Matt Etterson
Sep 30, 2013 EDSP Tier 2 test (T2T) guidances and protocols are delivered, including web-based guidance for diagnosing and scoring, and evaluating EDC-induced pathology in fish and amphibian. Rodney Johnson
Sep 30, 2014 Basic version of a fish toxicity translator model for extrapolation to population level effects along with user’s manual and technical support manual. Matt Etterson

Sep 30, 2014

Report on the relationships between early gene expression, growth, pathology and reproductive outcomes in fish exposed to chemicals with various AOPs.

Rodney Johnson

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