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Abstract: Twenty‐six polycyclic aromatic compounds (PACs; including native polycyclic aromatic hydrocarbons [PAHs], hydroxylated PAHs, alkylated and oxygenated PAHs, and [alkylated] heterocyclic compounds) were investigated for their aryl hydrocarbon receptor (AhR)‐mediated potencies in the H4IIE‐luc bioassay. Potential degradabilities of PACs were investigated by use of various durations of exposure (24, 48, or 72 h), and various mixtures of PACs including PAHs, alkylated and oxygenated PAHs, and heterocyclic compounds were tested for their joint AhR‐mediated potency. Additive behaviors of PACs in mixtures were studied by comparing observed mixture potencies with mixture potencies predicted by use of the concentration addition model. Methylated derivatives were more potent than their parent compounds in the H4IIE‐luc assay. A time‐dependent decrease in relative potency was observed for all AhR‐active compounds, which may be indicative of in vitro biotransformation. Monomethylated compounds seemed to be more rapidly transformed than analogous unsubstituted compounds. In addition, the results showed that the predictive power of the concentration addition model increased with the number of compounds, suggesting additivity in multicomponent mixtures. Due to the greater potency of methylated derivatives and their ubiquitous occurrence, there is a need for further research on the toxicity and mixture behavior of these environmentally and toxicologically relevant compounds. Environ Toxicol Chem 2018;37:1409–1419. © 2018 SETAC [ABSTRACT FROM AUTHOR]

As a consequence of ubiquitous use of brominated organic chemicals, there is a concern for persistent or increasing environmental levels of polybrominated dibenzo-p-dioxins/furans (PBDD/Fs) and mixed polychlorinated and polybrominated dibenzo- p-dioxins/furans (PXDD/Fs). Hence, there is a need to broaden the toxicological and environmental knowledge about these compounds, as a basis for risk assessment. In the study presented here, the relative potencies (REPs) for 18 PBDD/F and PXDD/ F congeners were determined in four dioxin-specific bioassays from different species: dioxin receptor chemically activated luciferase expression assay (DR-CALUX, rat hepatoma cells), TV101L (human hepatoma cells), and GPC.2D (guinea pig adenoma cells), as well as ethoxyresorufin-O-deethylase induction in the fish cell line RTL-W1 (rainbow trout liver cells). The bioassay specific REP factors presented here enable the assessment of the contribution from PBDD/Fs and PXDD/Fs to total 2,3,7,8-tetrachlorodibenzop- dioxin (TCDD) equivalents (TEQs: toxic equivalents), using bioassay analysis. The PBDD/Fs were found to be equally potent as their chlorinated analogues in the three mammalian assays, whereas the PXDD/Fs showed relatively higher potencies. Of special concern were the 2,3,7,8-substituted penta- and tetrahalogenated congeners, for which mean REPs were ≥1. The 2-B-1,3,7,8-CDD (2-bromo-1,3,7,8-tetrachlorodibenzo-p-dioxin) was up to three times more potent than TCDD in individual experiments (on weight basis). The RTL-W1 was less sensitive to the tested compounds with overall 10-fold lower REPs than the mammalian cell lines. Although the REP factors exhibited species-specific differences, overall resembling rank orders of dioxin-like potency were obtained. [ABSTRACT FROM AUTHOR]