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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
repeated dose toxicity: oral
Adequacy of study:
other information

Data source

Reference
Reference Type:
other: Body responsible for the test
Title:
Unnamed

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: EEC Directive 92/69, B.7
GLP compliance:
yes
Limit test:
no

Test animals

Species:
other: rat, Wistar Crl:(WI) BR

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
other: Dry propylene glycol (<0.2%)
Details on oral exposure:
Method of administration:
gavage
Duration of treatment / exposure:
Test duration: 28 days
Frequency of treatment:
Dosing regime: 7 days/week
No. of animals per sex per dose:
Male: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 5 mg/kg bw/day
Male: 5 animals at 25 mg/kg bw/day
Male: 5 animals at 125 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 5 mg/kg bw/day
Female: 5 animals at 25 mg/kg bw/day
Female: 5 animals at 125 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:
Clinical observations:
At 125 mg/kg/day:

All animals died or were killed in extremis between day 9
and 10 of treatment.

Prior to death of or sacrifice, hunched posture or pale skin
was observed among males and lethargy, ventro-lateral
recumbency, hunched posture, uncoordinated movements, pale
skin, quick breathing, ptosis and/or piloerection were
observed in all females.

Body weights and food consumption reduced in week 1.

At 25 mg/kg/day only slightly low body weights were found in
females in week 4.

At 5 mg/kg/day no treatment-related findings noted.

Laboratory findings:
No clinical laboratory investigations were performed on the
animals receiving 125 mg/kg/day, due to mortality or interim
sacrifice of the animals of this dose group during the
study.

At 25 mg/kg/day a decrease in erythrocyte cell count,
haemoglobin and hematocrit in females only.

At 5 mg/kg/day no treatment-related findings noted.

Effects in organs:
At 125 mg/kg/day:

Macroscopic post mortem examination of the animals revealed
changes in the stomach, liver, kidneys, adrenal glands,
spleen, mesenteric lymp node and lungs.

Microscopic correlations to the findings noted at
macroscopic examination were found in the stomach
(hyperplasia with hyperkeratosis, inflammation), liver
(vacuolation, hypertrophy, pigment deposits (bile ducts),
coagulative kidneys (tubular degeneration, females only),
spleen (haemopoiesis), mesentric lymph nodes
(hyperplasia)and adrenal glands vacuolation of cortex.

No treatment-related effects were found at animals of the 5
and 25 mg/kg/day dose groups.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
25 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day.
Dose descriptor:
NOEL
Effect level:
5 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Classified as: Xn - harmful