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New Approach Methodologies to Prioritize and Identify Key Components of UVCBs
Citation:
Phillips, A., J. McCord, B. Blackwell, K. Houck, AND E. Ulrich. New Approach Methodologies to Prioritize and Identify Key Components of UVCBs. SETAC North America 41st Annual Meeting. Virtual Conference, RTP, NC, November 15 - 19, 2020. https://doi.org/10.23645/epacomptox.13138604
Impact/Purpose:
Poster presented to the SETAC North America 41st Annual Meeting. Virtual Conference. November 2020
Description:
It is estimated that over half of chemicals in commerce are classified as chemical substances of unknown or variable composition, complex reaction products and/or biological materials (UVCBs). Individual UVCBs are poorly defined at the chemical structure and weight fraction levels, making traditional exposure and risk assessment methodologies poorly suited for evaluating UVCB safety. This research proposes using new approach methodologies for the effect-directed prioritization of UVCB components for non-targeted chemical structure identification. UVCBs will be initially characterized by high resolution mass spectrometry (HRMS) using full-scan (m/z 150-2,000) MS1 data collected in both positive and negative electrospray ionization modes. Following characterization, subfractions will be collected using a liquid chromatography system to reduce mixture complexity. UVCBs and their associated fractions will then be assessed in parallel bioaccumulation and bioactivity assays. The metabolism and bioaccumulation potential of individual UVCB features will be estimated via a substrate depletion approach using an incubation system with human liver subcellular fractions and metabolic cofactors. Bioactivity of individual UVCB fractions will be evaluated for interaction with 24 human nuclear receptors in the liver HepG2 cell line. Features and fractions scoring the highest in both assays will be prioritized for further fractionation, additional bioactivity testing, and in-depth structural characterization using non-targeted, HRMS techniques. The efficacy of this approach will be tested in case studies with two commercial UVCBs: a surfactant and a nonylphenol mixture. Generated data will aid modelers in assessing UVCB exposure and hazard potential in support of risk assessment for complex chemical mixtures.
URLs/Downloads:
DOI: New Approach Methodologies to Prioritize and Identify Key Components of UVCBs
PHILLIPS_SETAC2020_UVCBPOSTER.PDF (PDF, NA pp, 606.912 KB, about PDF)