Some of the enzymes were induced in a long- term oral administration study at doses as low as approximately 1 μmol/kg/day, and the enzyme activities continued 30–60 days after termination of the exposure ( 89 ). The full- brominated decaBDE, however, appears to have low enzyme-inducing potency. The effects of BDE-47 and Aroclor 1254 on microsomal enzyme induction was studied in Sprague-Dawley rats ( 90 ). Induction of EROD and 7-methoxyresorufin- O -deethylase activities by BDE-47 was limited, in contrast to the marked induction (> 100-fold) in Aroclor-exposed animals. The effect on the pentoxyresorufin analog, known to describe CYP2B activity, was, on the other hand, almost the same after treatment with both BDE-47 and Aroclor 1254. If induction capacity is indicative of metabolic pathways of these compounds, the CYP2B enzymes may be important in the metabolism of PBDEs. In a recent study using a recombinant rat hepatoma cell line H4IIE with a luciferase reporter gene, several PBDE congeners acted as Ah-receptor agonists ( 91 ). In this model potencies of the agonists were comparable to those of some mono- ortho PCBs. Some PBDE congeners also had antagonistic effects on TCDD-induced luciferase production. Halogenated dioxinlike compounds typi- cally induce CYP1A1 and 1A2. Therefore, enzyme induction may be due to impurities with Ah-receptor binding affinity present in technical PBDE mixtures. It was shown that PCDF impurities at concentrations < 1% could completely account for the observed EROD activity of all except one of 29 tested polychlorinated diphenyl ether (PCDE) con- geners ( 92 ). This study demonstrated that in studies with halogenated DEs, it is important to control the presence of potent dibenzofuran and dibenzodioxin impurities, which even at low concentrations can account for consider- able biologic activity attributed to the relatively high dosages required for DEs. The outcome of this study is in agreement with structural considerations suggesting that the nonplanarity of halogenated DEs results in a low binding affinity to the Ah receptor ( 93 ). Nevertheless, some studies have shown that pure PCDEs indeed are weak inducers of microsomal EROD and AHH activities in a congener- and conformation-specific manner ( 94–97 ). In studies on phase II induction, three different PBDE fractions were tested; i.e., low (24% tetra, 50% penta) and high (45% hepta, 30% octa) brominated mixtures, and the decaBDE congener only. After daily oral administrations (14 days, 0.1 mmol/kg bw), both of the mixtures, but not the decaBDE, resulted in long-lasting induction of uridine diphosphate glucuronyltransferase (UDPGT) activity in rats ( 88 ). Human Data As mentioned previously, PBDEs are found in human blood and tissues and in human breast milk. Data show that PBDEs are also absorbed and retained in man and that BDE- 47 is the most abundant congener in most cases. Today, data are too limited to estimate the degree of human bioavailability and bioac- cumulation. However, Sjödin ( 98 ) estimated the elimination half-lives of certain PBDE congeners in humans. Calculations were based
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- Spring '13
- The Land, Baltic Sea, Polychlorinated biphenyl, Brominated flame retardant, Flame retardant, Decabromodiphenyl ether, PBDE