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EC number: 222-182-2
CAS number: 3380-34-5
BLOOD/PLASMA LEVELS AND KINETICS
PLASMA, SINGLE GAVAGE
in males after single
oral administration the Cmax values were reached after 4 hours and increased
about 11 times from 19.48 ± 5.26 pg peq/g to 212.8 ± 12.0 pg peq/g at
the low and at
the high dose levels, respectively.At similar half-lives (9-12 hours)
AUC-levels increased about 27 times from 166 to 4505 pg peq/g x hour for
the low (2.4 mg/kg) and the high dose (200 mg/kg) groups, respectively.
In females Cmax values
were reached at 2-4 hours after administration and increased about 34
fold from 7.67 pg peq/g to 263.3 pg peq/g at the low and at the high
dose levels, respectively. At similar half-lives of 9-10 hours,
corresponding AUC-levels increased about 53 times from 119 to 6322 pg
peq/g x hour for the low (2.0 mg/kg) and the high dose (204 mg/kg)
groups, respectively. At the last sampling interval of 96 hours, plasma
levels in the females were about 2-3 times lower than the corresponding
values in the males.
BLOOD, SINGLE GAVAGE (females)
Similar to plasma, in
females the Cmax values were reached after 1 and 4 hours and increased
about 27 times from 5.49 pg peq/g to 141.7 - 148.2 pg peq/g at the high
dose level. The corresponding AUC-levels increased 49 times from 70 to
3409 pg peq/g x hour for the female groups. Analogously to plasma at
about 100 fold higher dose levels, AUC values increased only about 50
times. Blood levels were always significantly lower at each sequential
sampling interval indicating that protein binding of either triclosan or
its metabolites were minimal.
BIORETENTION IN ORGANS/TISSUES AND
on plasma, liver and kidney were performed at both dose levels after single
and repeated oral administration to male mice. For the low dose level
after repeated (13x) food supply, the Cmax value in plasma was 3-fold
lower than after single low dose administration. In liver and kidney
these values were similar. At ¼ and 1/8 Cmax, values in plasma, liver
and kidney were 3-6 times lower after repeated (13x) food supply against
single oral administration. These results suggest already some
saturation in plasma after repeated administration at the low dose level.
For the corresponding
high dose level groups at
Cmax and ½ Cmax, the values in plasma, liver and kidney were
approximately 50 % less in the group receiving the repeated (13x) food
supply than in the single dose group. At ¼ and 1/8 Cmax, the values in
plasma (1.6 times) and in liver as well as kidney (1.1 -1.2 times) were
less pronouncely reduced. The results suggest partial saturation in
absorption after repeated administration at the high dose level.
As compared to plasma,
kidney concentrations from Cmax to 1/8 Cmax were about 2 times lower
throughout all groups. These results indicate efficient elimination of
triclosan and/or metabolites
from the kidney at both dose levels (single and repeated). As compared
to plasma, liver concentrations from Cmax to1/8 Cmax were similar or
lower after single oral administration at both dose levels. In contrast,
after repeated administration at both dose levels, values from Cmax to 1/8
Cmax in liver were always higher than in the plasma (about
1.1 - 1.5 times) indicating that the liver in the mouse is a specific
target organ after
repeated administration of triclosan.
PLASMA TOXICOKINETICS OF14C-TRICLOSAN AFTER
SINGLE ORAL ADMINISTRATION AT TWO DOSE LEVELS TO MALE AND FEMALE MICE
Actual Dose Level [mg/kg bw]
AUChigh dose/ AUClow dose
Time interval after regression [h]
Regression coefficient R
* Based on lnCt=lnC0- k1× t (first order elimination kinetics)** Sacrifice time
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