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Application of High-Throughput Toxicokinetics in the Assessment of PFAS
Citation:
Wetmore, B. AND J. Wambaugh. Application of High-Throughput Toxicokinetics in the Assessment of PFAS. 2020 ToxForum Winter Meeting, Mclean, Virginia, January 27 - 28, 2020. https://doi.org/10.23645/epacomptox.19232646
Impact/Purpose:
This presentation will be given at the 2020 ToxForum winter meeting in Mclean, VA. Entitled "Application of High-Throughput Toxicokinetics in the Assessment of PFAS," it describes the contribution that in vitro or high-throughput chemical toxicokinetics makes to the interpretation of in vitro toxicity testing data, which are increasingly being utilized as "new approach" chemical safety assessment tools. Toxicokinetics (TK) is an area of research that considers the role of chemical absorption, distribution, metabolism and excretion in the body to understand blood, and tissue levels, which are ultimately important in framing the impact of a particular chemical exposure on human health. The focus in this talk is on per- and polyfluoroalkyl substances (PFAS) - for which only very limited in vivo toxicokinetic and toxicity data are currently available. The talk will describe how the available data have been used thus far to understand PFAS TK, the strategy to generate additional data, and preliminary findings of work conducted to date, along with future plans to utilize experimental in vitro TK data to inform TK modeling efforts and computational prediction (e.g., quantitative-structure activity relationship (QSAR)) tools.
Description:
New approach methodologies (NAMs) make use of in vitro high-throughput data and in silico approaches to translate in vitro bioactivities to administered dose equivalents for safety assessment. Per- and polyfluoroalkyl substances (PFAS) have become chemicals of concern for human health as more is learned about their widespread presence and persistence in the environment. The availability of in vivo toxicologic data and exposure information on only a subset of PFAS is inadequate to provide an understanding of the potential exposures and toxicokinetics (TK) across this diverse domain. To date, toxicokinetic assessments across in vivo studies have indicated the value that incorporation of such information has on in vivo study interpretation. This work has informed the experimental strategy that is now being pursued to generate experimental in vitro measures of chemical toxicokinetics (e.g., plasma protein binding, hepatic clearance) across a panel of PFAS selected to cover a wide range of PFAS with varied functional groups. This presentation will provide an update on progress made to date along with future plans and efforts in the development of PFAS TK in silico models. This abstract does not necessarily reflect NIEHS or EPA policy.
URLs/Downloads:
DOI: Application of High-Throughput Toxicokinetics in the Assessment of PFAS
WETMORE_PRESENTATION_TOXFORUM.PDF (PDF, NA pp, 2690.659 KB, about PDF)