Relative Potencies of Individual Polychlorinated Naphthalenes and Halowax Mixtures To Induce Ah Receptor-Mediated Responses

Abstract

Polychlorinated naphthalenes (PCNs) are ubiquitous environmental pollutants that are structurally similar to other polychlorinated diaromatic hydrocarbons (PCDHs), such as polychlorinated dibenzo- p -dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls (PCBs). Despite being ubiquitous, much less is known about the fate, transport, and biological effects of individual PCN congeners than other PCDHs. The purpose of the current study was to utilize an in vitro assay (H4IIE-luc) to determine potencies relative to 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) for 20 individual PCNs (from 75 possible congeners) and 6 Halowax mixtures. H4IIE rat hepatoma cells (H4IIE-Luc), which are stably transfected with an Ah receptor (AhR)-controlled luciferase reporter gene construct, respond specifically to AhR agonists and are thus a reasonable 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 to TCDD of 0.004, 0.001, and 0.001, respectively. Significant structure−activity relationships were observed. For example, lateral substitution is an important determinant of AhR-mediated activity, but not sufficient, as illustrated by the inactivity of 2,3,6,7-tetra-CN to elicit AhR-mediated activity. Relative potencies of the Halowax mixtures with AhR-mediated activity were 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 to assess the potential contribution of PCNs to total TCDD equivalents (TEQs) in environmentally weathered complex mixtures.