Enzyme induction and histopathology elucidate aryl hydrocarbon receptor–mediated versus non–aryl hydrocarbon receptor–mediated effects of Aroclor 1268 in American mink (Neovison vison)

Abstract

Polychlorinated biphenyl (PCB) concentrations reported in preferred prey and blubber of bottlenose dolphins from the Turtle-Brunswick River estuary (Georgia, USA) suggest the potential for adverse effects. However, PCBs in Turtle-Brunswick River estuary dolphins are primarily derived from Aroclor 1268, and predicting toxic effects of Aroclor 1268 is uncertain because of the mixture's unique composition and associated physiochemical characteristics. These differences suggest that toxicity benchmarks for other PCB mixtures may not be relevant to dolphins exposed to Aroclor 1268. American mink (Neovison vison) were used as a surrogate model for cetaceans to characterize mechanisms of action associated with Aroclor 1268 exposure. Mink share similarities in phylogeny and life history with cetaceans and are characteristically sensitive to PCBs, making them an attractive surrogate species for marine mammals in ecotoxicity studies. Adult female mink and a subsequent F1 generation were exposed to Aroclor 1268 through diet, and effects on enzyme induction, histopathology, thyroid hormone regulation, hematology, organ weights, and body condition index were compared to a negative control and a 3,3',4,4',5-pentachlorobiphenyl (PCB 126)-positive control. Aroclor 1268 dietary exposure concentrations ranged from 1.8 µg/g wet weight to 29 µg/g wet weight. Anemia, hypothyroidism, and hepatomegaly were observed in mink exposed to Aroclor 1268 beyond various dietary thresholds. Cytochrome P450 induction and squamous epithelial proliferation jaw lesions were low in Aroclor 1268 treatments relative to the positive control. Differences in enzyme induction and the development of squamous epithelial proliferation jaw lesions between Aroclor 1268 treatments and the positive control, coupled with effects observed in Aroclor 1268 treatments not observed in the positive control, indicate that mechanisms additional to the aryl hydrocarbon receptor-mediated pathway are associated with Aroclor 1268 exposure.

Growth and reproductive effects from dietary exposure to Aroclor 1268 in mink (Neovison vison), a surrogate model for marine mammals

“…Whelp success and litter size were adversely affected, although reproduction was not completely inhibited, which was expected given that the concentrations of the positive control diets (90.2 ng ΣTEQ/g feed wet wt and 132 ng ΣTEQ/g feed wet wt) fall between the previously reported reproductive diet‐based NOEC and LOEC for PCB 126 from Beckett et al of 24 ng ΣTEQ/g feed wet weight and 240 ng ΣTEQ/g feed wet weight, respectively. Histopathology of juvenile positive control mink jaws revealed a 100% incidence of severe squamous epithelial proliferations, which supports the assumption that the present study mink were characteristically sensitive to PCB exposure given that the exposure concentration was greater than 10 times the PCB 126 level demonstrated to cause severe jaw lesions .…”

“…The first and second batches of positive control diets were spiked with 0.899 ng PCB 126/g feed wet weight and 1.31 ng PCB 126/g feed wet weight, respectively (Table ). Polychlorinated biphenyl 126 was selected as the positive control to evaluate the mode(s) of action for Aroclor 1268 . Treatment diets were prepared based on an established formula that satisfies the nutritional requirements of mink .…”

“…Prior to necropsy, whole blood was collected from dams and juvenile mink for plasma PCB analysis and thyroid hormone quantification in serum . Blood collection was not performed on kits due to insufficient blood volume for analysis.…”

“…Liver, kidneys, spleen, heart, thymus, brain, uterus, jaws, and adrenal and thyroid glands were removed, weighed, and examined by a board‐certified pathologist for gross abnormalities. Organs were stored in 10% neutral buffered formalin for histopathological examination, described in a concurrent publication . All samples destined for analytical chemistry (diet, adipose, liver, plasma) were collected and stored in certified chemically clean glass jars at –25 °C until contaminant analyses could be performed.…”

Enantioselective Toxicity in Adult Zebrafish (Danio rerio) Induced by Chiral PCB91 through Multiple Pathways

“…Moreover, long-term exposure to toxic chemicals may result in irreversible effects on sensitive tissues . For example, a group of adult female American mink ( Neovison viso n) fed with Aroclor 1268 displayed trace mineralization of renal tubules, unilateral pyelitis, and interstitial nephritis . Moreover, a PCB126 dose was associated with slightly hepatic vacuolization in C57BL/6 mice .…”