Biomarker activities were annotated when the data from the sample at 2 or more consecutive concentrations changed in the same direction relative to vehicle controls outside of the significance envelope and had at least one concentration with an effect size > 20% (|log10 ratio| > 0.1). Biomarker key activities were described as modulated if these activities increased in some systems but decreased in others. Cytotoxic conditions were noted when total protein levels decreased by >50% (log10 ratio values of SRB or alamarBlue < −0.3). A test article was considered to have broad cytotoxicity when cytotoxicity was detected in 3 or more systems. Concentrations of test articles with detectable broad cytotoxicity were excluded from biomarker activity annotations and further analyses. Antiproliferative effects were defined by an SRB or alamarBlue |log10 ratio|value < −0.1 from cells plated at a lower density. Annotation of cytotoxicity and antiproliferative effects only required one concentration to be considered as such.
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