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

Environ Toxicol Chem. 2016 Mar;35(3):619-34. doi: 10.1002/etc.3203. Epub 2016 Feb 5.

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.

Keywords: Cytochrome P450; Ecotoxicology; Mammalian toxicology; Polychlorinated biphenyl; Toxicity mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / chemistry
  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • Animals
  • Aroclors / chemistry*
  • Aroclors / metabolism
  • Aroclors / toxicity
  • Bottle-Nosed Dolphin / growth & development
  • Bottle-Nosed Dolphin / metabolism
  • Diet
  • Enzyme Induction
  • Female
  • Georgia
  • Hepatomegaly / pathology
  • Hepatomegaly / veterinary
  • Hypothyroidism / pathology
  • Hypothyroidism / veterinary
  • Liver / chemistry
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mink / growth & development
  • Mink / metabolism
  • Models, Animal
  • Organ Size / drug effects
  • Polychlorinated Biphenyls / toxicity
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Thyroid Hormones / blood
  • Water Pollutants, Chemical / chemistry*
  • Water Pollutants, Chemical / metabolism
  • Water Pollutants, Chemical / toxicity

Substances

  • Aroclor 1268
  • Aroclors
  • Receptors, Aryl Hydrocarbon
  • Thyroid Hormones
  • Water Pollutants, Chemical
  • Polychlorinated Biphenyls
  • 3,4,5,3',4'-pentachlorobiphenyl