Carcinogenic activity of pentabrominated diphenyl ether mixture (DE-71) in rats and mice. (2018)

• Record Type: Journal Article
• Authors: Dunnick, J.K.; Pandiri, A.R.; Merrick, B.A.; Kissling, G.E.; Cunny, H.; Mutlu, E.; Waidyanatha, S.; Sills, R.; Hong, H.L.; Ton, TV.; Maynor, T.; Recio, L.; Phillips, S.L.; Devito, M.J.; Brix, A.
• Is Part Of: Toxicology reports. Volume 5(2018)
• Page Start: 615
• Page End: 624
• Publication Date: 2018
• Subjects: Pentabrominated diphenyl ethers -- Liver toxicity -- Carcinogenic activity; Toxicology -- Periodicals; Clinical toxicology -- Periodicals; Drug-Related Side Effects and Adverse Reactions; Hazardous Substances; Poisoning; Toxicology; Electronic journals; Periodicals; Periodicals; 571.9505
• DOI: 10.1016/j.toxrep.2018.05.010
• Languages: English
• ISSNs: 2214-7500

Abstract

Graphical abstract: Highlights: Pentabrominated diphenyl ether (PBDE) mixture was a multispecies carcinogen causing liver tumors in male and female rats and mice. Hras or Ctnnb1 mutations characterized the PBDE-induced liver tumors. PBDE-induced liver tumors increased with increasing PBDE exposure. Abstract: 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.