Relative potencies of individual polychlorinated naphthalenes and halowax mixtures to induce Ah receptor-mediated responses

Polychlorinated naphthalenes (PCNs) are ubiquitous environmental pollutants that are structurally similar to other polychlorinated diaromatic hydrocar bons (PCDHs), such as polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofur ans (PCDFs), and biphenyls (PCBs). Despite being ubiquitous, much less is k nown about the fate, transport, and biological effects of individual PCN co ngeners than other PCDHs. The purpose of the current study was to utilize a n in vitro assay (H4IIE-luc) to determine potencies relative to 2,3,7,8-tet rachlorodibenzo-p-dioxin (TCDD) for 20 individual PCNs(from 75 possible con geners)and 6 Halowax mixtures. H4IIE rat hepatoma cells (H4IIE-Luc), which are stably transfected with an Ah receptor (AhR)-controlled luciferase repo rter gene construct, respond specifically to AhR agonists and are thus a re asonable measure of AhR-mediated, or dioxin-like, activity. The most potent congeners were 1,2,3,4,6,7-hexa-CN (PCN 66), 1,2,3,5,6,7-hexa-CN (PCN 67), and 1,2,3,4,5,6,7-hepta-CN (PCN 73), with relative potencies as compared t o TCDD of 0.004, 0.001, and 0.001, respectively. Significant structure-acti vity relationships we re observed. For example, lateral substitution is an important determinant of AhR-mediated activity, but not sufficient, as illu strated by the inactivity of 2,3,6,7-tetra-CN to elicit AhR-mediated activi ty. Relative potencies of the Halowax mixtures with AhR-mediated activity w ere 0.0089, 0.000038, and 0.0000018 for 1051, 1014, and 1013, respectively. The relative potencies derived from this study were applied to literature- derived data on concentrations of PCN congeners in environmental mixtures t o assess the potential contribution of PCNs to total TCDD equivalents (TEQs ) in environmentally weathered complex mixtures.