In vivo reporter gene mutation and micronucleus assays in gpt delta mice treated with a flame retardant decabromodiphenyl ether.

Polybrominated diphenyl ethers (PBDEs), a class of brominated flame retardants, have been widely used as additive flame retardants. Recently, the use of brominated flame retardants has been restricted or prohibited under various legislative acts because of the persistence, bioaccumulation potential, and toxicity of these compounds. However, there are also additional concerns regarding environmental contamination and human exposure to PBDEs resulting from informal recycling technology. Decabromodiphenyl ether (decaBDE), one type of PBDE, has carcinogenic potential in the livers of rodents. Although one study has shown that decaBDE exerts genotoxic effects, the other in vitro and in vivo studies were negative for such effects. Thus, it remains unknown whether genotoxic mechanisms are involved in decaBDE-induced hepatocarcinogenesis in rodents. In this study, to explore the genotoxicity of decaBDE in mice, particularly in the context of carcinogenesis, we performed micronucleus assays in the bone marrow and reporter gene mutation assays in the liver using gpt delta mice treated with decaBDE at carcinogenic doses for 28days. Our results demonstrated negative results in micronucleus tests and reporter gene mutation assays. Thus, decaBDE did not exert genotoxic effects at carcinogenic target sites and did not show positive results in conventional in vivo genotoxicity tests in mice for 4-week treatment. Overall, comprehensive evaluation using in vivo genotoxicity data in rats and our data indicated that nongenotoxic mechanisms may be responsible for decaBDE-induced hepatocarcinogenesis.