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Integrative modeling approaches for insight into the behavior of per- and polyfluorinated alkyl substances (PFAS) across scales and ecosystems
Citation:
Weiziao, C., J. Doering, C. LaLone, AND C. Ng. Integrative modeling approaches for insight into the behavior of per- and polyfluorinated alkyl substances (PFAS) across scales and ecosystems. Association of Environmental Engineering and Science Professors, Tempe, AZ, May 14 - 16, 2019.
Impact/Purpose:
Per- and polyfluorinated alkyl substances (PFAS) from consumer, industrial, and firefighting applications have been detected in the environment. They have been found in drinking water and in organisms, including humans. There are limited data available evaluating the effects of these substances to human health or the environment. Therefore, efforts are underway to generate as much information as possible in this area. Importantly, PFAS are known to stick around in the environment for long periods of time and accumulate in tissue. Scientists are conducting studies to understand how these PFAS accumulate in mammalian species, like humans and rats. However, there is limited understanding of the bioaccumulation of PFAS in other species. It is therefore important to understand if PFAS are likely to accumulate in other species similarly to mammals. Fortunately, there are computer tools that can assist us in understanding the likelihood for bioaccumulation of PFAS in other species, using the information that has been generated for mammalian species. Here we employ a combination of these computational methods to evaluated PFAS bioaccumulation across species to inform further toxicity testing on species likely to have differences in the way they interact with and therefore accumulate PFAS.
Description:
Recent estimates suggest that per- and polyfluorinated alkyl substances (PFAS), as a class, may include nearly 5000 different structures. Many of these are “emerging” PFAS, having very little property and effects data. Because of their extreme persistence and broad use in consumer, industrial, and firefighting applications, PFAS are ubiquitous in the environment and increasingly detected in drinking water and in the bodies of wildlife and humans. Understanding the potential impacts of chronic exposure to these complex mixtures is thus a research priority. Due to the wide variety of PFAS structures currently in the environment and the expense (e.g., time, resources, animal use) associated with chemical-by-chemical testing approaches, reliable structure-activity relationships and other predictive modeling approaches are being explored to enhance understanding of potential effects across taxa. Model-based approaches can facilitate high-throughput screening and prioritization, and provide valuable insight into the behavior of PFAS mixtures. Here, integrative strategies are described that combine gene-based, molecular- and organism-scale models of PFAS fate and behavior within biological systems. Through evaluation of interactions with key tissue-specific receptors, these models provide valuable insights into relative PFAS bioaccumulation potential across species. This talk will focus on complementary approaches that leverage molecular dynamics, the US EPA’s Sequence Alignment to Predict Across Species Susceptibility tool (https://seqapass.epa.gov/seqapass/), and physiologically based pharmacokinetic models to identify and probe key molecular targets across diverse species. These approaches hold promise for facilitating in silico to in vitro to in vivo extrapolation, and further demonstrate how the integration of structure- and species-specific information may inform future research and decision-making.