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EC number: 203-313-2
CAS number: 105-60-2
The test substance was rapidly absorbed from the stomach
and was distributed throughout all animals including fetuses. There was
efficient elimination by the kidney and liver, material secreted by the
liver into bile and intestinal contents appeared not to be reabsorbed
via an enterohepatic circulation. The kinetics of distribution and
elimination appeared to be the same in female and pregnant animals. The
only sites of retention of radioactivity after 24 hr (excluding renal
and hepatic) were in umbilical cords, amnion, yolk sac, maternal lens,
maternal Harder's gland, and maternal liver. The distribution into and
removal from the fetuses was typical of molecules that freely diffuse
across the placenta. There was no retention in any fetal tissue. No
localization was seen that would suggest a site of toxic action except
for that possibility in nasal epithelium.
Table 1. Distribution of radioactivity in male
rats at intervals following the oral distribution of 0.18 mg (14C)
test substance /kg bw.
Time after dosing (h)
Values are the means ± SEM of 5 determinations
* including contents
level of radioactivity was too low for accurate measurement
nodes were excised from the serosal surface of the small intestine
was taken from the supratesticular fat pad
Table 2. The test substance and its two
major metabolites in the urine of rats dosed orally with 0.18 mg
[14C]test substance/kg bw*
Percentage of total urinary radioactivity after dosing (h)
Metabolite I (MI)
78.1 ± 3.6
79.3 ± 2.4
Metabolite II (MII)
16.9 ± 3.7
17.7 ± 2.1
3.9 ± 1.2
2.3 ± 0.6
* Values are means ± SD for three determinations.
The publication describing the tissue distribution and
excretion of [14C]test substance in male Fischer 344 rats given a single
oral dose of 0.18 mg/kg bw is well documented and acceptable with
restrictions. After 24 hr, 77.6% of the administered radioactivity was
excreted in the urine, 3.5% in the feces and 1.5% in the expired air of
the animals. Elimination of radioactivity in the urine and expired air
was most rapid during the initial 6 hr following dosing. Analysis of the
urine indicated that after 24 hr, only 2.3% of the excreted
radioactivity was in the form of the parent compound. Two major urinary
metabolites of the test substance (MI and MII) were detected comprising
79.3% and 17.7% of the excreted radioactivity, respectively, in the
The test substance appears to be absorbed rapidly after
single inhalation exposure with blood peak level after approx. 4 h.
Excretion was also rapid with no detectable test substance in urine
after 20 h.
The relation of maximal serum concentration of 21:1 is
reflecting the relation of 26:1 in the inhalation atmosphere.
Table 1. The distribution of radioactivity in the tissues
of non-pretreated (control) and pretreated male rats 6 hr following the
oral administration of 1500 mg/kg bw
Distribution of radioactivity (mg equivalents test substance/g tissue)
Values are the means (±SEM) of five or six determinants.
The percentage increases shown by significantly values were 69%
(kidneys), 57% (aorta) and 75% (fat).
Table 2. The test substance and its two
major metabolites in the urine of rats dosed orally with 1500 mg
[14C]test substance/kg bw*
25.1 ± 2.4
59.5 ± 4.8
14.1 ± 6.4
15.7 ± 5.7
55.2 ± 7.2
14.7 ± 3.5
The publication describing the disposition of [14C]-test
substance given a single dose of 1500 mg/kg bw in rats is well
documented and is acceptable with restrictions. The pattern of tissue
distribution of radioactivity, 6 hr after administration of the high
dose differed little from that observed after the low dose (as
documented in another endpoint study record), except high presence of
the radioactivity in the stomach and low excretion of the radioactivity
in urine. Pretreatment with the test substance for 7 days had little
effect on the tissue distribution, and urinary and faecal excretion.
Based on the studies in rats and mice, the test substance appears to be absorbed rapidly. Excretion is also rapid and predominantly via the urine, mainly in metabolized form with only a small portion of the dose being excreted unchanged.
There are few reliable studies on the tissue distribution and excretion
of radioactive labeled or unlabeled test substance in rat, mice and
24 hr after a single oral dose of 0.18 mg/kg bw [14C] test substance
No indication of an enrichment of radioactivity in a specific tissue was
found throughout the observation period. This is additionally
demonstrated by comparable tissue/blood levels of radioactivity, a
monophasic tissue clearance and a similar tissue distribution/excretion
pattern of radioactivity following pretreatment with unlabeled test
substance for 7 days (1.5g/kg bw [14C] test substance). In
particular low liver tissue levels of radioactivity indicate that the
liver may play a limited role in caprolactam metabolization.
Analysis of the urine indicated that after 24 hr, only 2.3% of the
excreted radioactivity was in the form of the parent compound. Two major
urinary metabolites of the test substance (MI and MII) were detected
comprising 79.3% and 17.7% of the excreted radioactivity, respectively.
With increasing dosage (1500mg/kg bw) the amount of parent compound
recovered in urine increased substantially (14.7.2%) indicating a
saturable metabolism. The identity of both metabolites was not further
These experiments were confirmed by a whole-body autoradiography study
in which tissue distribution of gavaged [14C]-test substance was studied
in female and 14.5-day-pregnant mice (Badische Corp., 1981). [14C]-test
substance was rapidly absorbed from the stomach and was uniformly
distributed throughout the animals including fetuses and brains. A
similar tissue distribution was observed in male mice intravenously
injected with [14C]-test substance (see below).
There was efficient elimination by the kidney and via bilary secretion
as shown by radioactive labeling. The only sites of retention of
radioactivity after 24 hr (excluding renal and hepatic) were in
umbilical cords, amnion, yolk sac, maternal lens, maternal Harder's
gland, and maternal liver. But there was no retention in any fetal
Further confirmation was provided in an oral study in which male rabbits
and rats were singly dosed with 300 mg/kg bw test substance (Bayer,
1977). Absorption and excretion of the test substance was rapid with
blood peak levels after approx. 4 h and excretion predominantly via
urine and to a minor degree in feces.
Four ninhydrin-positive compounds (metabolites A, B, C and D) were
identified in urine of rats exposed to 46 mg/kg bw day over a time
period of 2-3 weeks (Kerschner Kirk et al., 1987). 19% of the consumed
dose was recovered in the urine in the form of these 4 metabolites.
Metabolites A and D, 6-amino-4-hydroxyhexanoic acid and the
corresponding lactone, accounted for 87.5% of the four metabolites. Both
(A and D) were shown to be a free acid and lactone pair in equilibrium
under acidic conditions. Apparently hydroxylation of the lactam in the
γ-position is a major metabolic pathway. 6-Aminohexanoic acid
(metabolite C) represented 8.8% and the unidentified metabolite B 3.7%.
Following a single inhalation exposure of male Wistar rats to aerosols
of 0.531 and 0.02 mg/l for 2-6 h, the test substance was rapidly
absorbed (Bayer, 1977).
With a high exposure concentration of 0.531 mg/l a rapid increase in the
test substance serum-concentration was observed. With an exposure period
of 4h the peak serum-concentration of 37 µg/ml was identified after 4 h.
20 h after onset exposure, no test substance was detectable in the
serum. Similar findings were observed low dose exposure atmosphere of
0.020 mg/l. With both atmospheres the test substance was rapidly
excreted via urine during the first 24 h after exposure.
As with single doses, repeated inhalation exposure with 0.025 mg/l for 5
days (6 h/day) resulted in rapid test substance absorption and
excretion. No test substance was detected in the plasma ahead of each of
the subsequent exposures and therefore no commutation occurred (Bayer,
No information is available.
Other routes of exposure:
Badische Corp. (1981) studied distribution of [14C]-test substance in
male mice by whole-body autoradiography after administrating 6.4-6.9
mg/kg bw (7.1-8.2 µCi/mouse) intravenously. By 20 min, there was uniform
distribution throughout the mouse. Apart from renal and hepatic
elimination, the only sites of residual radioactivity at 9 hr in the
male were nasal epithelium and the olfactory lobe of the brain.
Additionally, there was significant amount of radioactivity in the lens
of the eye and in Harder's gland.
Following a single ip. injection of the test substance (300mg/kg bw) in
rats and rabbits the test substance was rapidly absorbed and excreted
within 20h after application (Bayer, 1977). ε-aminocaproic acid was
identified as a major metabolite in urine. In relation to urinary test
substance the amount excreted in rabbits was higher compared to rats.
For both, the test susbtance and ACA, renal excretion occurred
predominatly during the first 48 h.
Intra-tracheal injection of the test substance (1, 10 mg/kg bw) in rats
resulted in a more rapid increase of the test substancev plasma levels
compared to oral or inhalation exposure.
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