Characterization of liver toxicity in F344/N rats and B6C3F1 mice after exposure to a flame retardant containing lower molecular weight polybrominated diphenyl ethers

Abstract

Lower molecular weight polybrominated diphenylethers (PBDEs), components of flame retardants, are found in the environment and in human and animal tissues. Toxicity studies were conducted in F344/N rats and B6C3F1 mice by administering a flame retardant containing these lower molecular weight PBDEs (BDE-47, BDE-99, BDE-100, and BDE153) by oral gavage 5 days/week for 13 weeks at doses of 0.01, 5, 50, 100 or 500 mg/kg/day. Liver was the primary target organ in rats and mice. Treatment-related increases in liver weights, liver cytochrome P450 (1A1, 1A2, 2B) and UDPGT (rats only) levels, and liver lesions were seen in both rats and mice. Hepatocyte hypertrophy and vacuolization increased in incidence and severity with treatment, and occurred at levels of 50 mg/kg and above in rats, and at 100 mg/kg and above in mice. Liver Cyp 1A1, 1A2, and 2B levels were increased at exposure levels of 50 mg/kg and above in rats and mice. In addition, treatment-related thyroid lesions occurred particularly in rats. The most sensitive parameter for PBDE toxicity was the increase in liver weights which occurred at 5 mg/kg above in rats and 50 mg/kg and above in mice. These results suggest that liver may be a target organ for carcinogenesis processes after long-term administration of PBDEs. A chronic PBDE study is currently being conducted by the National Toxicology Program.

Effects of exposure to BDE-99 on oxidative status of liver and kidney in adult rats

“…This differs from the results of other recent studies where hepatic cell damages were found (Raldúa et al, 2008;Dunnick and Nyska, 2009). Factors such as different animal species and doses could explain these differences.…”

“…It has been reported that oral exposure to lower brominated congeners induces hepatic hypertrophy and increases liver weight (IPCS, 1994;Dunnick and Nyska, 2009). Moreover, a number of studies have shown that exposure to PBDEs seems to induce an increase in hepatic microsomal enzyme activities involved in the metabolism of xenobiotics (Zhou et al, 2001;Wolkers et al, 2009).…”

Characterization of Polybrominated Diphenyl Ether Toxicity in Wistar Han Rats and Use of Liver Microarray Data for Predicting Disease Susceptibilities

“…This liver toxicity in the Wistar Han rat is similar to that observed in the F344/N rat after PBDE exposures (Dunnick and Nyska 2009). Hepatocellular vacuolization, as seen in PBDE rat livers, is often indicative of accumulation of fat deposits (Eustis et al .…”

Evaluation of liver and thyroid toxicity in Sprague-Dawley rats after exposure to polybrominated diphenyl ether BDE-209

“…PBDE-induced liver toxicity and alterations in liver enzyme levels, and, thus, metabolic activation is a likely mechanism for this toxicity. Dunnick and Nyska (2009) demonstrated that increases in liver weights and induction of liver cytochrome P450 (1A1, 1A2, 2B) and UDPGT levels were observed in both rats and mice after BDE-exposure. In addition, hepatocyte hypertrophy and vacuolization increased in incidence and severity with treatment, and occurred at levels of 50 mg/ kg and above in rats.…”