Current Perspectives on the Use of Alternative Species in Human Health and Ecological Hazard Assessments

Abstract

Background: 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.Objective: We compared several types of data to demonstrate how alternative models can be used to inform both human and ecological risk assessment.Methods: We reviewed and compared data derived from high throughput in vitro assays to fish reproductive tests for seven chemicals. We investigated whether human-focused assays can be predictive of chemical hazards in the environment. We examined how conserved pathways enable the use of nonmammalian models, such as fathead minnow, zebrafish, and Xenopus laevis, to understand modes of action and to screen for chemical risks to humans.Results: We examined 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. We also examined how development/safety data for human health can be used to help assess potential risks of pharmaceuticals to nontarget species in the environment.Discussion: Using several examples, we demonstrate that pathway-based analysis of chemical effects provides new opportunities to use alternative models (nonmammalian species, in vitro tests) to support decision making while reducing animal use and associated costs.Conclusions: 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.Citation: Perkins EJ, Ankley GT, Crofton KM, Garcia-Reyero N, LaLone CA, Johnson MS, Tietge JE, Villeneuve DL. 2013. Current perspectives on the use of alternative species in human health and ecological hazard assessments. Environ Health Perspect 121:1002–1010; http://dx.doi.org/10.1289/ehp.1306638

Development and application of the adverse outcome pathway framework for understanding and predicting chronic toxicity: I. Challenges and research needs in ecotoxicology

“…Due to similarities in molecular mechanisms that lead to toxicological outcomes, AOPs also provide a defensible framework for extrapolating chemical effects across species, thus allowing a broader integration of all available information and generation of robust hypotheses to be tested (Perkins et al, 2013). For example, in the case of pharmaceutical micropollutants, the existing knowledge on their actions in mammals can be used to develop AOPs (Brausch et al, 2012), which along with evaluation of molecular targets conservation could help in predicting relevant toxicity outcomes in other species of concern, such as fish (Gunnarsson et al, 2008;Domingo et al, 2010).…”

“…The usefulness of the AOP framework for cross-species extrapolations has been highlighted previously (Celander et al, 2011;Perkins et al, 2013) and several examples of how toxicokinetic and toxicodynamic processes contribute to differences in species sensitivity have been given above. Below, we will briefly discuss how AOPs can be used to support common strategies applied for species extrapolation (Section 4.1) and present a venue for a broader integration of evolutionary life history theory with AOP concept, which could be developed into another useful approach to cross-species extrapolation (Section 4.2).…”

Pathways and factors for food safety and food security at PFOS contaminated sites within a problem based learning approach

“…From the same study, US EPA (2009a,b) derived a TDI of 80 ng kg À1 bw, accounting for an extrapolation factor based on the toxicokinetics differences in humans, and animals. It seems worthy to note that the above modeled TDIs might need re-assessment on the evidences of other toxicological end-points such as sperm quality (Joensen et al, 2009) or delayed pregnancy (Fei et al, 2009) having been observed in the average population being exposed to considerable lower level than the TDI and within a combined exposure assessment, also targeted on the identification of Adverse Outcome Pathways via alternative methods based on high throughput screening tests (Perkins et al, 2013).…”

Tebuconazole disrupts steroidogenesis in Xenopus laevis

“…The steroidogenic pathway is well conserved among species (Perkins et al, 2013) allowing for extrapolation of results across vertebrate classes and to other steroid-producing organisms.…”