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The fish early life-stage (FELS) test (OECD Test Guideline 210) is the primary test used internationally to estimate chronic fish toxicity in support of ecological risk assessments and chemical management programs. As part of an on-going effort to develop efficient and cost-effective alternatives to the FELS test, there is a need to identify and describe potential adverse outcome pathways (AOPs) relevant to FELS toxicity. To support this endeavor, we outline and illustrate an overall strategy for discovery and annotation of FELS AOPs. Key events represented by major developmental landmarks were organized into a preliminary conceptual model of fish development. Using swimbladder inflation as an example, a weight-of-evidence-based approach was used to support linkage of key molecular initiating events to adverse phenotypic outcomes and reduced young-of-year survival. Based on an iterative approach, we explored the feasibility of using key events as the foundation for expanding a network of plausible linkages and AOP knowledge and, in the process, identify important knowledge gaps. Given the scope and scale of the task, prioritization of AOP development was recommended and key research objectives were defined relative to factors such as current animal use restrictions in the European Union and increased demands for fish toxicity data in chemical management programs globally. The example and strategy described are intended to guide collective efforts to define FELS-related AOPs and develop resource-efficient predictive assays that address the toxicological domain of the OECD 210 test.

Background: Over the past 10-15 years, a substantial amount of work has been done by the scientific, regulatory, and business communities to elucidate the effects and risks of pharmaceuticals and personal care products (PPCPs) in the environment. Objective: This review was undertaken to identify key outstanding issues regarding the effects of PPCPs on human and ecological health in order to ensure that future resources will be focused on the most important areas. Data sources: To better understand and manage the risks of PPCPs in the environment, we used the "key question" approach to identify the principle issues that need to be addressed. Initially, questions were solicited from academic, government, and business communities around the world. A list of 101 questions was then discussed at an international expert workshop, and a top-20 list was developed. Following the workshop, workshop attendees ranked the 20 questions by importance. Data synthesis: The top 20 priority questions fell into seven categories: a) prioritization of substances for assessment, b) pathways of exposure, c) bioavailability and uptake, d) effects characterization, e) risk and relative risk, f) antibiotic resistance, and g) risk management. Conclusions: A large body of information is now available on PPCPs in the environment. This exercise prioritized the most critical questions to aid in development of future research programs on the topic. ; Centro de Investigaciones del Medioambiente

Background: Over the past 10-15 years, a substantial amount of work has been done by the scientific, regulatory, and business communities to elucidate the effects and risks of pharmaceuticals and personal care products (PPCPs) in the environment. Objective: This review was undertaken to identify key outstanding issues regarding the effects of PPCPs on human and ecological health in order to ensure that future resources will be focused on the most important areas. Data sources: To better understand and manage the risks of PPCPs in the environment, we used the "key question" approach to identify the principle issues that need to be addressed. Initially, questions were solicited from academic, government, and business communities around the world. A list of 101 questions was then discussed at an international expert workshop, and a top-20 list was developed. Following the workshop, workshop attendees ranked the 20 questions by importance. Data synthesis: The top 20 priority questions fell into seven categories: a) prioritization of substances for assessment, b) pathways of exposure, c) bioavailability and uptake, d) effects characterization, e) risk and relative risk, f) antibiotic resistance, and g) risk management. Conclusions: A large body of information is now available on PPCPs in the environment. This exercise prioritized the most critical questions to aid in development of future research programs on the topic. ; Fil: Boxall, Alistair B. A. University of York; Reino Unido ; Fil: Rudd, Murray A. University of York; Reino Unido ; Fil: Brooks, Bryan W. Baylor University; Estados Unidos ; Fil: Caldwell, Daniel J. Johnson & Johnson; Estados Unidos ; Fil: Choi, Kyungho. Seoul National University; Corea del Sur ; Fil: Hickmann, Silke. Umweltbundesamt; Alemania ; Fil: Innes, Elizabeth. Health Canada; Canadá ; Fil: Ostapyk, Kim. Health Canada; Canadá ; Fil: Staveley, Jane P. Exponent; Estados Unidos ; Fil: Verslycke, Tim. Gradient; Estados Unidos ; Fil: Ankley, Gerald T. United States Environmental Protection Agency; Estados Unidos ; Fil: Beazley, Karen F. Dalhousie University Halifax; Canadá ; Fil: Belanger, Scott E. Procter And Gamble; Estados Unidos ; Fil: Berninger, Jason P. Baylor University; Estados Unidos ; Fil: Carriquiriborde, Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química. Centro de Investigaciones del Medio Ambiente; Argentina ; Fil: Coors, Anja. Ect Oekotoxikologie Gmbh; Alemania ; Fil: DeLeo, Paul C. American Cleaning Institute; Estados Unidos ; Fil: Dyer, Scott D. Procter And Gamble; Estados Unidos ; Fil: Ericson, Jon F. Pfizer Inc.; Estados Unidos ; Fil: Gagné, François. Environment Canada; Canadá ; Fil: Giesy, John P. University of Saskatchewan; Canadá ; Fil: Gouin, Todd. Unilever; Reino Unido ; Fil: Hallstrom, Lars. University of Alberta; Canadá ; Fil: Karlsson, Maja V. University of York; Reino Unido ; Fil: Joakim Larsson, D.G. University of Göteborg; Alemania ; Fil: Lazorchak, James M. United States Environmental Protection Agency; Estados Unidos ; Fil: Mastrocco, Frank. Pfizer Inc.; Estados Unidos ; Fil: McLaughlin, Alison. Health Canada; Canadá ; Fil: McMaster, Mark E. Environment Canada; Canadá ; Fil: Meyerhoff, Roger D. Eli Lilly And Company; Estados Unidos ; Fil: Moore, Roberta. Health Canada; Canadá ; Fil: Parrott, Joanne L. Environment Canada; Canadá ; Fil: Snape, Jason R. AstraZeneca UK Ltd.; Reino Unido ; Fil: Murray-Smith, Richard. AstraZeneca UK Ltd.; Reino Unido ; Fil: Servos, Mark R. University of Waterloo; Canadá ; Fil: Sibley, Paul K. University of Guelph; Canadá ; Fil: Straub, Jürg Oliver. F. Hoffmann-La Roche Ltd.; Suiza ; Fil: Szabo, Nora D. University of Ottawa; Canadá ; Fil: Topp, Edward. Agriculture Et Agroalimentaire Canada; Canadá ; Fil: Tetreault, Gerald R. University of Waterloo; Canadá ; Fil: Trudeau, Vance L. University of Ottawa; Canadá ; Fil: Van Der Kraak, Glen. University of Guelph; Canadá