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Current perspectives on the use of alternative species in human health and ecological hazard assessments
Citation:
Perkins, E., G. Ankley, K. Crofton, N. Garcia-Reyero, C. LaLone, M. Johnson, Joe Tietge, AND Dan Villeneuve. Current perspectives on the use of alternative species in human health and ecological hazard assessments. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, 121(9):1002-1010, (2013).
Impact/Purpose:
Proposals to make increasing and more effective use of in vitro, high throughput, in silico, and other types of “alternative” toxicity data in chemical screening and hazard assessment has placed increased emphasis on the use of mechanistic information to support chemical safety/hazard assessment. As the assessment paradigm shifts toward a more mechanistic focus, traditional distinctions between data appropriate to support human health versus ecological assessments are disappearing. Instead, with an understanding of toxicity pathways and the conservation of those pathways among taxa, it is increasingly feasible to utilize human health-oriented data (e.g., those generated using traditional human health models like rodents or human cell lines) to predict ecological outcomes and likewise to use data from alternative animal models like fish, frogs, invertebrates, etc. to predict human health outcomes. This review article provides case studies and perspectives related to this change in paradigm and the increasing opportunity for increased integration of human health and ecological toxicity. Case studies include applications with direct relevance to EPA programs, such as the applicability of Toxcast data for ecological hazard assessment and comparability of mammalian and fish EDSP data, and the development and application of 21st century approaches to toxicity testing – a central theme under EPA’s Chemical Safety for Sustainability research program.
Description:
Traditional animal toxicity tests can be time and resource intensive thereby limiting the number of chemicals that can be comprehensively tested for potential hazards to humans and/or to the environment. Using several examples and analyses, we demonstrate that pathway-based analysis of chemical effects provide new opportunities to use alternative models (non-mammalian species, in vitro tests) to support robust decision making, while reducing animal use and associated costs. For example, we compared data derived from high-throughput in vitro assays to fish reproductive tests for seven chemicals, and show that human-focused assays can be predictive of chemical hazards in the environment. We also discuss how conserved pathways enable the use of non-mammalian models, e.g., fathead minnow, zebrafish and Xenopus laevis, to understand toxic modes of action and screen for chemical risks to humans. As an extension of this we illustrate how dose-dependent responses of zebrafish embryos exposed to flusilazole can be extrapolated, using pathway point of departure data and reverse toxicokinetics, to obtain human oral dose hazard values that are similar to published mammalian chronic toxicity values for the chemical. In another example, we address how development/safety data for human health can be used to help assess potential risks of pharmaceuticals to non-target species in the environment. These analyses and examples demonstrate how alternative models can be used to reduce cost and animal use while being protective of both human and ecological health. It is expected that implementation of 21st century approaches to chemical risk assessment will blur the distinctions between the disciplines of human health and ecotoxicology leading to a more unified and integrated application of toxicological data.
