Carcinogenic activity of pentabrominated diphenyl ether mixture (DE-71) in rats and mice

J.K. Dunnick; A.R. Pandiri; B.A. Merrick; G.E. Kissling; H. Cunny; E. Mutlu; S. Waidyanatha; R. Sills; H.L. Hong; TV. Ton; T. Maynor; L. Recio; S.L. Phillips; M.J. Devito; A. Brix

Toxicology Reports (Jan 2018)

Carcinogenic activity of pentabrominated diphenyl ether mixture (DE-71) in rats and mice

J.K. Dunnick,
A.R. Pandiri,
B.A. Merrick,
G.E. Kissling,
H. Cunny,
E. Mutlu,
S. Waidyanatha,
R. Sills,
H.L. Hong,
TV. Ton,
T. Maynor,
L. Recio,
S.L. Phillips,
M.J. Devito,
A. Brix

Affiliations

J.K. Dunnick: National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA; Corresponding author at: National Institute of Environmental Health Sciences, P.O. Box 27709-2233, Research Triangle Park, NC 27709, USA.
A.R. Pandiri: National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
B.A. Merrick: National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
G.E. Kissling: National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
H. Cunny: National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
E. Mutlu: National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
S. Waidyanatha: National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
R. Sills: National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
H.L. Hong: National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
TV. Ton: National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
T. Maynor: Integrated Laboratory Systems, Research Triangle Park, NC 27709, USA
L. Recio: Integrated Laboratory Systems, Research Triangle Park, NC 27709, USA
S.L. Phillips: Integrated Laboratory Systems, Research Triangle Park, NC 27709, USA
M.J. Devito: National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
A. Brix: EPL, Inc., Research Triangle Park, NC 27709, USA

Journal volume & issue: Vol. 5
pp. 615 – 624

Abstract

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Pentabrominated diphenyl ether (PBDE) flame retardants have been phased out in Europe and in the United States, but these lipid soluble chemicals persist in the environment and are found human and animal tissues. PBDEs have limited genotoxic activity. However, in a 2-year cancer study of a PBDE mixture (DE-71) (0, 3, 15, or 50 mg/kg (rats); 0, 3, 30, or 100 mg/kg (mice)) there were treatment-related liver tumors in male and female Wistar Han rats [Crl:WI(Han) after in utero/postnatal/adult exposure, and in male and female B6C3F1 mice, after adult exposure. In addition, there was evidence for a treatment-related carcinogenic effect in the thyroid and pituitary gland tumor in male rats, and in the uterus (stromal polyps/stromal sarcomas) in female rats. The treatment-related liver tumors in female rats were unrelated to the AhR genotype status, and occurred in animals with wild, mutant, or heterozygous Ah receptor. The liver tumors in rats and mice had treatment-related Hras and Ctnnb mutations, respectively. The PBDE carcinogenic activity could be related to oxidative damage, disruption of hormone homeostasis, and molecular and epigenetic changes in target tissue. Further work is needed to compare the PBDE toxic effects in rodents and humans. Keywords: Pentabrominated diphenyl ethers, Liver toxicity, Carcinogenic activity

Published in Toxicology Reports

ISSN: 2214-7500 (Online)
Publisher: Elsevier
Country of publisher: Ireland
LCC subjects: Medicine: Public aspects of medicine: Toxicology. Poisons
Website: http://www.journals.elsevier.com/toxicology-reports/

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