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EC number: 254-052-6
CAS number: 38640-62-9
DIPN is absorbed and metabolized quite fast after administration and
might accumulate in fat tissue during repeated exposure. In fat,
elevated levels are attained. But the concentration reached is dependent
on dose and not on duration of exposure. Thus extended exposure will
presumably not result in continuing accumulation of DIPN. Based on
dosage a maximal level (steady state) will be reached without further
accumulation. After cessation of exposure, elimination of DIPN from fat
will occur with a half-life of approx. 50 to 300 h (biphasic elimination
Information on DIPN
DIPN is absorbed from the
gastrointestinal tract quite rapidly (Kawai/Iwahara 1974). It is
distributed in the body and peak levels in blood and organs are reached
within about 2 h (single dose administration). In adipose tissue, peak
levels are attained considerably later (24 h p.a.). Tissue concentration
in fat (ca. 90 µg/g) is higher than in other tissues (≤ ca. 30 µg/g).
DIPN is cleared from organs quite rapidly and elimination is complete
after 48 h. In fat, ca. 70% of the peak level is still found after 48 h
(Hazegawa 1982_in vivo).
After repeated dose oral
administration, final tissue levels are dependent on dose but not on
exposure period (Anbe 1980). Organ concentrations of DIPN are in the
same order as for single administration. But fat levels are doubled.
Clearance of DIPN from organs is quite rapid and complete within 1 to 3
d thus comparable with single dose administration. In fat, elimination
is much slower with still 4% DIPN present after 30 days (Hazegewa
Elimination from organs indicates
metabolic transformations. Metabolism was demonstrated by reaction of
DIPN with liver homogenates showing decomposition rates of 40 to 50%
within 2 h depending on the initial concentration (Hazegawa 1982_in
vitro). Metabolites of DIPN (labeled substrate) in urine have been
separated by TLC (Kawai/Iwahara 1974). But discrete metabolites of DIPN
have not yet been isolated and characterized.
After single oral administration of 3H
labeled DIPN, radioactivity is completely excreted within 96 h (30% in
urine, 70% in feces). Native DIPN was not detected (Kawai/Iwahara 1974).
Information on supporting substance
Comparable studies have been performed
with 2,6-DIPN. This compound will be used as supporting substance.
For 2,6-DIPN similar results on
absorption and distribution have been observed supporting the findings
for DIPN (Kojima 1978, Kojima 1979). In addition, five metabolites were
identified. In urine and bile, 40% of the total dose was excreted in
form of these metabolites within 24 h after single oral administration
of unlabeled native 2,6-DIPN. Two further metabolites were separated in
TLC without elucidation of their structure. The metabolites identified
are all transformed in the isopropyl side chain. The unidentified
metabolites are considered to be phenolic compounds due to reaction with
diazotized sulfanilic acid (Kojima 1982/1985).
DIPN is absorbed and metabolized quite fast after administration and is
not accumulated in organs during
repeated exposure. However,
levels are attained. But the concentration reached is dependent on dose
and not on duration of exposure. Thus extended exposure will
presumably not result
in continuing accumulation of DIPN. Based on dosage a maximal level
(steady state) will be reached without further accumulation. After
cessation of exposure, elimination of DIPN from fat will occur with a
half-life of approx. 50 to 300 h (biphasic elimination characteristics).
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