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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: Annex V, Method B7, Commission Directive 84/449/EECa
GLP compliance:
yes
Limit test:
no

Test animals

Species:
other: Sprague-Dawley Rats

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
other: 1% w/v aqueous Methylcellulose
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 15 mg/kg bw/day
Male: 5 animals at 150 mg/kg bw/day
Male: 5 animals at 1000 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 15 mg/kg bw/day
Female: 5 animals at 150 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:
Clinical observations:
No deaths occurred.

No signs of ill health or behavioural changes were noted.


There were no notable differences in actual bodyweights and
no significant difference in overall body weight gains
between control and treated rats of both sexes.


Food consumption for all treated rats was comparable to that
of control animals.

Laboratory findings:
A statistically significant decrease in haemoglobin values
for males at the 150 and 1000mg/kg/day dose levels (i.e.
P<0.05) was noted. Also the thrombotest values for males at
all 3 dose levels were reduced significantly (i.e. P<0.05 to
P<0.01) compared to the controls.


Analysis of blood smears revealed the occurence of slight
polychromasia and/or slight anisocytosis. However this
finding is not uncommon among young laboratory rats and at
the incidence seen in this study was not considered to be
toxicologically important.


There were no notable differences in haematology for females
treated compared to controls.


Elevated Alkaline phosphatase values occurred at all dose
levels for both sexes achieving significance (P<0.05) for
high dose females.


Individual male animals exhibited raised Aspartate
aminotransferase at all dose levels, achieving statistical
significance for those at the 1000mg/kg/day, while one
female animal at 150mg/kg/day also achieved an elevated AST
level.


A slight reduction in the glucose values for females at 15
and 150mg/kg/day was noted compared to controls.

Effects in organs:
Decreased adjusted kidney weights were recorded for males at
15,150 and 1000mg/kg/day achieving statistical significance
compared to controls (P<0.05)


Elevated weights for ovaries were noted and achieved
statistical significance (P<0.05) at the 1000mg/kg/day dose
level.


One male rat at 1000mg/kg/day exhibited a slightly reduced
liver weight (not statistically significant).

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
150 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day.
Dose descriptor:
NOEL
Effect level:
15 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