Relative Potencies of Individual Chlorinated and Brominated Polycyclic Aromatic Hydrocarbons for Induction of Aryl Hydrocarbon Receptor-Mediated Responses

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Abstract
Chlorinated and brominated polycyclic aromatic hydrocarbons (ClPAHs and BrPAHs) occur as pollutants in the environment. Nevertheless, there is little information available regarding the toxic effects of ClPAHs and BrPAHs. The potencies of 19 individual ClPAHs and 11 individual BrPAHs to induce aryl hydrocarbon receptor (AhR)-mediated activities (i.e., dioxin-like toxicity), relative to the potency of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), were determined in vitro by use of a recombinant rat hepatoma cell (H4IIE-luc) assay. Several ClPAHs elicited AhR-mediated activity; the relative potencies (RePs) of 6-monochlorochrysene, and 7-monochlorobenz[a]anthracene were 2.6 × 10−5 and 6.3 × 10−6, respectively. Among BrPAHs, 7-monobromobenz[a]anthracene and 4,7-dibromobenz[a]anthracene had the highest RePs, 2.1 × 10−5 and 2.3 × 10−5, respectively. None of the chlorinated or brominated anthracene or fluorene compounds elicited AhR-mediated activity at the concentrations tested. We developed a structure−activity relationship for AhR-mediated potencies of ClPAHs. The RePs of ClPhe and ClFlu (low-molecular-weight ClPAHs) were directly proportional to the compounds’ degrees of chlorination. The RePs of higher-molecular-weight ClPAHs (≥4-rings) were lower than those of the corresponding parent PAHs. The RePs of BrPAHs were higher than the RePs of the corresponding ClPAHs. For instance, 6-BrBaP was more potent than 6-ClBaP and 7-BrBaA was more potent than 7-ClBaA. The RePs determined in this study were applied to literature concentrations of Cl- and Br-PAHs in environmental samples, to calculate dioxin-like toxicities, as toxic equivalents (TEQs). The TEQs of ClPAHs calculated using the concentrations of individual ClPAHs were 4.6 pg-TEQ/g in fly ash, 0.015 fg-TEQ/m3 in automobile exhaust, and 0.085 fg-TEQ/m3 in urban air. 6-ClChr accounted for 80% of the total ClPAHs-TEQs in fly ash. This is the first in vitro study to report AhR-mediated activities of Cl- and Br-PAHs relative to the activity of TCDD.