Toxicity of Bromkal 70-5DE, a technical mixture of polybrominated diphenyl ethers, following 28 d of oral exposure in rats and impact of analysed impurities

The subacute toxicity of a commercial polybrominated diphenyl ether (PBDE) preparation, Bromkal 70-5DE, was investigated. In addition to a vehicle control, the mixture was given orally to male and female Sprague-Dawley rats for 28d at three dose levels; 2.5, 25 and 250mgkg^-1 b.w.d^-1. The observed effects include increased hepatic EROD activity (from 2.5mgkg^-1d^-1); increased liver weight (males), increased PROD activity and depletion of hepatic retinoids (from 25mgkg^-1d^-1); and increased liver weight (females), marked histological changes in the liver and lungs, as well as increased serum parameters such as total protein, cholesterol and albumin (from 250mgkg^-1d^-1). Chemical analysis of the PBDE mixture with gas chromatography/mass spectrometry (GS/MS) showed impurities of polybrominated dibenzofurans and to a lesser extent dibenzodioxins, in total levels of about 7.0μgg^-1 of Bromkal technical mixture. The animals were thereby exposed to an estimated dose of dioxin-like equivalents corresponding to 1.3-131ng TEQkg^-1 b.w.d^-1. It cannot be ruled out that this level of impurities can explain the hepatic EROD induction and hepatic retinoid depletion, which are considered typical markers of toxicity mediated via the aryl hydrocarbon receptor (AhR).