Some of the enzymes were induced in a long term oral

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