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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
Guideline:
other: 96/54/EG, B.7
GLP compliance:
yes
Limit test:
no

Test animals

Species:
other: rat, Wistar HsdCpb:WU

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
other: 2 % Cremophor EL (v/v)
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 50 mg/kg bw/day
Male: 5 animals at 175 mg/kg bw/day
Male: 5 animals at 612 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 50 mg/kg bw/day
Female: 5 animals at 175 mg/kg bw/day
Female: 5 animals at 612 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:
Clinical observations:
Survival was not affected by the treatment. No animals died
during the study.

Clinical observations revealed no treatment-related clinical
findings at 612 mg/kg bw/d and below. There were no
toxicologically significant differences between treated and
control groups in both sexes for food consumption and body
weight. The water intake was statistical significantly
increased for males at >= 175 mg/kg bw/d.

There were no toxicologically significant differences
between treated and control groups in the functional
observational battery, motor and locomotor activity.

Laboratory findings:
Hematology and clinical biochemistry showed no
toxicologically significant differences between treated and
control groups in both sexes up to and including 612 mg/kg
bw/d.

Urinalysis revealed a decrease of pH values in males and an
increased incidence of epithelial cells in both sexes at 612
mg/kg bw/d.

Effects in organs:
There were no changes in organ weights and necropsy that
were considered to be an effect of treatment.

At microscopy diffuse hyperplasia of the urinary bladder
transitional epithelium was observed in animals of both
sexes at 612 mg/kg bw/d. The hyperplasia affected the whole
bladder circumference and was graded most frequently as
slight. Minimal or slight diffuse hyperplasia was also
observed in the transitional epithelium of the urethra in
several animals given the same dose level. Hypertrophy and
vacuolation of the adrenal cortex was detected in one female
at 612 mg/kg bw/d. Because a finding of that type is usually
not known from controls for this single case a treatment
relation could not be excluded.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
175 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day.
Dose descriptor:
NOEL
Effect level:
50 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: Not classified

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