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PLoS One. 2014 Aug 19;9(8):e104639. doi: 10.1371/journal.pone.0104639. eCollection 2014.

Toxicological profile of ultrapure 2,2',3,4,4',5,5'-heptachlorbiphenyl (PCB 180) in adult rats.

Author information

1
Department of Environmental Health, National Institute for Health and Welfare, Kuopio, Finland; Department of Environmental Science, University of Eastern Finland, Kuopio, Finland.
2
Department of Environmental Health, National Institute for Health and Welfare, Kuopio, Finland.
3
Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
4
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
5
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Elche (Alicante), Spain.
6
Department of Environmental Health, National Institute for Health and Welfare, Kuopio, Finland; Department of Biology of Physical Activity, University of Jyväskylä, Jyväskylä, Finland.
7
ISLAB Laboratory Centre, Kuopio, Finland.
8
Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.
9
Center of Toxicology, IPA - Institute for Prevention and Occupational Medicine, German Social Accident Insurance, Ruhr University of Bochum, Bochum, Germany.
10
Department of Physiology, University of Turku, Turku, Finland.
11
Department of Physiology, University of Turku, Turku, Finland; Department of Paediatrics, University of Turku, Turku, Finland.
12
Department of Anatomy and Cell Biology, University of Oulu, Oulu, Finland.
13
Institute for Environmental Studies, VU University Amsterdam, Amsterdam, The Netherlands.
14
Institute of Food Chemistry and Food Biotechnology, Justus-Liebig University, Giessen, Germany.
15
Department of Biochemistry, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
16
Chemistry Department, Umeå University, Umeå, Sweden.
17
Food Chemistry and Toxicology, University of Kaiserslautern, Kaiserslautern, Germany.

Abstract

PCB 180 is a persistent non-dioxin-like polychlorinated biphenyl (NDL-PCB) abundantly present in food and the environment. Risk characterization of NDL-PCBs is confounded by the presence of highly potent dioxin-like impurities. We used ultrapure PCB 180 to characterize its toxicity profile in a 28-day repeat dose toxicity study in young adult rats extended to cover endocrine and behavioral effects. Using a loading dose/maintenance dose regimen, groups of 5 males and 5 females were given total doses of 0, 3, 10, 30, 100, 300, 1000 or 1700 mg PCB 180/kg body weight by gavage. Dose-responses were analyzed using benchmark dose modeling based on dose and adipose tissue PCB concentrations. Body weight gain was retarded at 1700 mg/kg during loading dosing, but recovered thereafter. The most sensitive endpoint of toxicity that was used for risk characterization was altered open field behavior in females; i.e. increased activity and distance moved in the inner zone of an open field suggesting altered emotional responses to unfamiliar environment and impaired behavioral inhibition. Other dose-dependent changes included decreased serum thyroid hormones with associated histopathological changes, altered tissue retinoid levels, decreased hematocrit and hemoglobin, decreased follicle stimulating hormone and luteinizing hormone levels in males and increased expression of DNA damage markers in liver of females. Dose-dependent hypertrophy of zona fasciculata cells was observed in adrenals suggesting activation of cortex. There were gender differences in sensitivity and toxicity profiles were partly different in males and females. PCB 180 adipose tissue concentrations were clearly above the general human population levels, but close to the levels in highly exposed populations. The results demonstrate a distinct toxicological profile of PCB 180 with lack of dioxin-like properties required for assignment of WHO toxic equivalency factor. However, PCB 180 shares several toxicological targets with dioxin-like compounds emphasizing the potential for interactions.

PMID:
25137063
PMCID:
PMC4138103
DOI:
10.1371/journal.pone.0104639
[Indexed for MEDLINE]
Free PMC Article

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