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 28 d at three dose levels; 2.5, 25 and 250 mg kg(-1) b.w.d(-1). The observed effects include increased hepatic EROD activity (from 2.5 mg kg(-1)d(-1)); increased liver weight (males), increased PROD activity and depletion of hepatic retinoids (from 25 mg kg(-1)d(-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 250 mg kg(-1)d(-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 7.0 microg g(-1) of Bromkal technical mixture. The animals were thereby exposed to an estimated dose of dioxin-like equivalents corresponding to 1.3-131 ng TEQ kg(-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).
Oberg
Mattias
M
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. mattias.oberg@ki.se
Westerholm
Emma
E
Fattore
Elena
E
Stern
Natalia
N
Hanberg
Annika
A
Haglund
Peter
P
Wiberg
Karin
K
Bergendorff
Anders
A
Håkansson
Helen
H
D000284:Administration, Oral; D000818:Animals; D001572:Benzofurans / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism; D000072338:Dibenzofurans, Polychlorinated; D004785:Environmental Pollutants / Q000633:toxicity; D005260:Female; D005411:Flame Retardants / Q000008:administration & dosage / Q000633:toxicity*; D055768:Halogenated Diphenyl Ethers / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000378:metabolism
D001572:Benzofurans; D000072338:Dibenzofurans, Polychlorinated; D004785:Environmental Pollutants; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D000072317:Polychlorinated Dibenzodioxins; C063747:Bromkal 70; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1