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EC number: 202-163-5
CAS number: 92-52-4
groups, each consisting of 2 male and female BDF1 mice, were administered14C-biphenyl
via a single oral gavage at 900 mg/kg bw dose level. After
oral dosing, excreta (blood, urine, and feces) and selected tissues were
collected at different time points. Radioactivity
in collected excreta and tissues was determined and the pharmacokinetic
parameters for radioactivity in blood were also derived. Metabolite
profiling and identification were also conducted in selected urine and
analysis showed that urine was the primary route of elimination of 14C-biphenyl
derived radioactivity, through 168 hours post-dosing (69-81% of the
administered dose) with the majority eliminated during the first 24
hours post-dosing (56-82% of the total urinary excretion). Feces
accounted for ≤10% of the administered dose.
168 hours post-dosing, the potential radioactivity remained in the
issues (blood, carcass, liver, kidneys, GI tract, and skin) ranged from
0.06 to 0.09 % of the orally administered dose from biphenyl test
material, indicating no bioaccumulation in the mouse.
blood time-course of radioactivity from males and females administered
900 mg 14C-biphenyl/kg bw showed the test material was
rapidly absorbed, with a Tmaxof
within 2 hours post-dosing. The
of the radioactivity from blood was relatively quick during the alpha elimination
phase (t½α~6 hours) followed by a slower
elimination during the terminal beta phase
and 671hours). The
dose-corrected blood AUC was 2
-fold higher in female mice than male, indicating substantially higher
systemic bioavailability of biphenyl and/or metabolites in female mice
than in male mice.
major urinary metabolite, representing approximately 35-50% of the dose,
was identified as the glucuronide conjugate of mono-hydroxylated
addition, there were up to 20 other metabolites tentatively identified,
each representing <1% to ~3% of the dose; these included
at least 2 isomers of the sulphate conjugate of mono-hydroxy biphenyl,
totaling about 5% of the dose. Total
various sulphate and glucuronide conjugates of di-hydroxy biphenyls and
tri-hydroxy biphenyls represented half of the urinary activity. The
N-acetyl cysteine conjugate of mono-hydroxyl biphenyl in male and female
urine represented <1% of the dose. Unchanged
parent biphenyl was detected in the urine samples, representing <1% of
the dose. Little evidence of non-conjugated hydroxylated biphenyl in
the urines was found.
was found to be rapidly absorbed, highly metabolized and quickly
eliminated in the BDF1 mouse. Although
absorption was comparable between genders, systemic exposure to biphenyl
and/or metabolites was thus substantially higher in the female mouse, and
is consistent with the observed increased incidence of liver tumors in
BDF1 females at high biphenyl doses in the Umeda
et al., 2005 cancer
bioassay. The prolonged exposure to reactive biphenyl metabolites would
result in sex-specific liver
injury followed by tissue regeneration and thus be consistent with the
threshold MOA for liver tumors reported for the BDF1 female mice.
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