Supplemental files for Respirometric Screening and Characterization of Mitochondrial Toxicants Within the ToxCast Phase I and II Chemical Libraries

<p>These are the supplemental files for TOXSCI manuscript 19-0578 entitled, “Respirometric Screening and Characterization of Mitochondrial Toxicants Within the ToxCast Phase I and II Chemical Libraries”:</p> <p> </p><p>Supplemental Figure 1 shows the median fold inhibition for basal (A) and maximal (B) respiration phases for nine test chemicals represented as 18 internally-duplicated samples used to measure intra-assay reproducibility (red dashed lines show threshold used to define bioactivity).</p><p><br></p><p>Supplemental Figure 2 shows the temporal dose-response plots (median % initial respiration ± mad) for all 243 chemicals tested in Tier 2 RSA screening. </p><p><br></p><p>Supplemental Figure 3 shows the temporal dose-response plots (median % initial respiration ± mad) for all 149 ETCi chemicals tested in the EFA.</p><p><br></p><p>Supplemental Table 1 lists five QC metrics calculated using DMSO, fenpyroximate, and 2,4-dinitrophenol controls used to evaluate RSA performance.</p><p><br></p><p>Supplemental Table 2 lists the 1,042 ToxCast chemicals tested in this study with activity calls for each testing tier, proposed mechanism of mitochondrial toxicity for RSA-actives and the inhibited respiratory complex(es) for putative ETC inhibitors. Maximal test concentrations are in µM excepting those values exceeding 200, which are in µg/µL.</p><p><br></p><p>Supplemental File A delineates how the respirometric screening assay protocol differs from the commonly-used mitochondrial stress assay protocol and provides a rationale for those differences.</p><p></p>