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EC number: 701-068-0
CAS number: 2156592-58-2
Groups of five male and female SD-rats received octadecenylamine
(Genamin OL 100 D, vehicle sesame oil) by oral gavage at dose levels of
0,3.25,12.5 or 50 mg/kg bw/day for a period of 28 days. On day 29
animals were necropsied. In the control and high dose groups, additional
five male and females were examined and necropsied after a recovery
period of 14 days. The study design and examinations conducted were in
full accordance to the EU method B.7 (OECD 407) for subacute oral
toxicity (including neurobehavioral observation and functional
observation battery testing).
In a preliminary study on dose-range finding three males and
females received the test substance at doses of 25, 100 and 400 mg/kg
bw/d over a period of 14 days and surviving animals were necropsied on
day 15. After administration of 400 mg/kg bw/d one male and one female
died at days 4 and 7, respectively. The other animals of this dose group
were killed for animal welfare reasons. The animals of the 100 mg/kg
bw/d group showed clinical signs of impaired motility and respiration.
The male animals were clearly more sensitive than the female animals.
After administration of 25 mg/kg bw/d no symptoms were observed except
of one female rat, which showed uncoordinated gait at study day 2. The
body weight gains of animals exposed to doses of 25 and 100 mg/kd bw/d
were impaired. Necropsy of the descendent and prior killed animals
showed changes in the stomach and intestinal mucosa. The animals of 100
mg/kg bw/d showed reddening of the stomach mucosa. No macroscopically
visible changes were observed in the 25 mg/kg dose groups.
In the main study, treatment resulted in no unscheduled deaths
throughout the study. Behaviour and state of health remained unaffected
by the administration of the test compound in the low and mid dose
groups. Clinical findings in the high dose group (2 males and 5 females
out of 10) from the 2nd or 3rd week onwards comprised impairments of
motility (stilted and/or uncoordinated gait) and lasted until the end of
treatment, with subsequent recovery. In addition, respiratory sounds
were noted in one high dose female only on study day 13. No opacity of
the refracting media of the eyes, changes of the oral mucosa, or
impairment of dental growth was observed. No abnormal neurobehavior was
observed in any group.
weight was significantly lower for high dose males from study day 11 and
for high dose females from day 22 until the end of treatment, and
remained to be different as compared to the controlat the end of
recovery period. Also mean body weights for mid dose males were
significantly lower from day 22 onwards to the end of treatment.
Compared to control animals, mean body weight gain was
significantly lower at the end of treatment for high dose males (-19%),
high dose females (-20%) and for mid dose males (-15%). A
dose-dependent, small (-9%, statistically non-significant) reduction of
body weight gain was also reported for the low dose males. The weight
gain was normalised at the end of the recovery for high dose males or
even higher in the high dose female group indicating a tendency to
recovery (no recovery conducted for the mid dose group). Food
consumption remained unaffected throughout the study in all dose groups.
Hematology findings in high dose groups included significantly
increased hematocrit and decreased reticulocyte counts (males only) and
slightly increased white blood cell counts with a shift towards
increased neutrophils (both genders), all findings being reversible.
Clinical chemistry changes comprised significantly increased total
bilirubin for the high dose group, slightly increased urea nitrogen for
mid and high dose females and very slightly increased ASAT and ALAT
activity in the liver of high dose males. Urinalysis remained unaffected
in all dose groups. Likewise the urine sediment was unobtrusive for
control and high dose group animals.
No anatomic pathology correlates (organ weights, macroscopy,
microscopy) of toxicological significance were detected.
In conclusion, repeated administration of Genamin OL 100 D
(octadecenylamine) at a dose of 50 mg/kg bw/day induced clinical signs
as gait abnormalities, reduction in body weight gain and clinical
pathology findings indicating mild toxic effects on the liver and
kidneys. The only treatment-related effects observed at the mid-dose
level were reduction in growth and increased urinary concentration of
urea nitrogen. By standard requirements on screening for neurotoxicology
given for this type of study, stilted gait or uncoordinated gait was not
associated with any other symptom of altered neurobehavior or
neurotoxicity and may be discussed as being of unspecific nature. In the
preliminary study, macroscopic findings in the gastrointestinal mucosa
were observed in early deaths and in animals receiving 100 mg/kg bw/d,
but were absent in animals at a dosage of 25 mg/kg bw/d from the 14-day
study and in dose groups receiving 50 mg/kg bw/d.
Except for growth reduction, full recovery of findings was seen at
the end of recovery period.
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