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Evaluating Metabolomics as a New Approach Method (NAM) for Toxicity Testing and Environmental Monitoring: An Assessment of IVIVE in Zebrafish
Citation:
Collette, Tim, J. Mosley, Q. Teng, J. Cavallin, Dan Villeneuve, AND Y. Yue. Evaluating Metabolomics as a New Approach Method (NAM) for Toxicity Testing and Environmental Monitoring: An Assessment of IVIVE in Zebrafish. 2022 SETAC North America Annual Meeting, Pittsburgh, PA, November 13 - 17, 2022.
Impact/Purpose:
Platform presentation at Society of Environmental Toxicology and Chemistry North American meeting communicates current developements in efforts to improve in vitro to in vivo extrapolation for effective monitoring of impacted surface waters.
Description:
The development of new approach methodologies (NAMs) to assess human and ecological toxicity to priority chemicals is an active area of research for national and international regulatory agencies. Recently, efforts have begun to utilize NAMs for evaluating biological impacts from complex contaminant mixtures to support risk assessments by EPA’s Regional and Program Offices. Due to the complexity of these exposures, it has been recognized that successful implementation will require high throughput approaches capable of collecting large numbers of relevant endpoints in an untargeted fashion. Metabolomics has been identified as a promising approach and is now a proven untargeted technique for capturing in vitro responses to a wide variety of contaminant mixtures in surface waters. However, there remains a dearth of information regarding the strengths and limitations of common in vitro models for translating metabolomic responses to in vivo systems (i.e., in vitro to in vivo extrapolation or IVIVE). Zebrafish are increasingly being used as a model test species for evaluating the toxicity of priority contaminants and for assessing risks associated with exposures to complex mixtures in the environment. This includes the use of the zebrafish model with both in vivo- and in vitro-based test systems. Here we present an untargeted mass spectrometry-based comparison of the hepatic metabolomes collected from unexposed (i.e., control) lab-reared adult zebrafish and the zebrafish liver cell line (ZFL) cultured in clean (i.e., control) media. This analysis revealed metabolites and biochemical pathways that are shared between the in vitro- and in vivo-based test systems, and thus more useful for extrapolation and prediction of adverse outcomes in exposure scenarios. Conversely, metabolites and biochemical pathways that are not shared (specifically those only found in vitro) are also identified and recommended for deprioritization for effects-based testing. The contents of this abstract neither constitute nor reflect US EPA policy.
