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, and A. Brix.
Toxicology Reports (2018) DOI: https://doi.org/10.1016/j.toxrep.2018.05.010 PMID: 29868454

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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.

Tables

Table 1. Littering Parameters for Wistar Han rats after in utero/postnatal exposure.

Table 1 (39 KB)

Table 2. Survival and final mean body weight for male and female rats and mice.

Table 2 (39 KB)

Table 3. Treatment-related carcinogenic effects in male and female Wistar Han rats and B6C3F1 mice.

Table 3 (49 KB)

Table 4. Selected treatment-related nonneoplastic lesions of liver and thyroid in male and female rats and mice.

Table 4 (47 KB)

Table 5. Hras and Ctnnb1 Mutations in liver tumors in male and female rats.

Table 5 (33 KB)

Table 6. Hras and Ctnnb1 mutations in hepatocellular carcinomas in mice.

Table 6 (43 KB)

Table 7. AhR genotyping of female rats.

Table 7 (41 KB)