Enzyme Induction and Acute Endocrine Effects in Prepubertal Female Rats Receiving Environmental PCB/PCDF/PCDD Mixtures

Abstract

Air, subsurface soil, and superficial dust from a National Priorities List landfill located in southern Illinois were sampled to determine their potential toxicities. The major components of these landfill extracts were polychlorinated biphenyls (PCBs), with significant amounts of polychlorinated dibenzofurans (PCDFs) and small amounts of polychlorinated dibenzodioxins (PCDDs). The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxic equivalency factor approach has been proposed to estimate the toxic potency of complex mixtures of chlorinated aromatics for environmental risk assessment. However, most components of environmental residues are nonplanar and do not act as aryl hydrocarbon (Ah) receptor agonists, so there is a great risk of not identifying adverse responses that are not dioxinlike. We used a 2-day prepubertal female rat bioassay to examine multiple biological responses, including both dioxinlike and nondioxinlike effects from these landfill extracts. As expected, both types of effects were detected. The soil and dust extracts produced similar dose-response relationships for 7-ethoxyresorufin O-deethylase, 7-pentoxyresorufin O-depentylase, 7-benzyloxyresorufin O-debenzylase, and 4-nitrophenol UDP-glucuronyltransferase induction; the dose response for the air extract deviated from the other two extracts. Soil, dust, and air extracts effectively reduced serum total thyroxine (T4) with similar dose-response relationships, despite the significantly different TCDD toxic equivalent (TEQ) values of these three extracts. Both soil (346 mg PCB/kg) and air (175 mg PCB/kg) extracts caused a greater than 30% increase in uterine wet weight. This study suggests that a more comprehensive approach is required to improve current risk assessment of environmental mixtures. TCDD TEQs reflect only a portion of effects and may especially underpredict effects on T4.