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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
other: Body responsible for the test
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Annex VI
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
other: Rat (Sprague-Dawley)

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
other: Distilled water
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 150 mg/kg bw/day
Male: 5 animals at 500 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 150 mg/kg bw/day
Female: 5 animals at 500 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:
Clinical observations:
Mortality data:

There were no deaths during the study.


Clinical observations:

No clinically observable signs of toxicity were detected in
test or control aniamls throughout the study period.

Increased salivation was detected prior to and/or
approximately two minutes after dosing in 1000 or 500
mg/kg/day animals from Days 4 or 5 respectively together
with incidents of fur wetting. This was considered to be a
consequence of an unpalatable or slightly irritant test
material formulation and was considered not to be indicative
of toxicity.


Functional observations:

There were no adverse treatment-related behavioural,
functional performance or sensory reactivity effects
observed.


Bodyweight:

No adverse effect on bodyweight development was detected.


Food consumption:

No adverse effect on dietry intake was detected.


Water consumption:

No intergroup differences were detected.

Laboratory findings:
Haematology:

No treatment-related effects were detected.


Blood chemistry:

In females, small but dose-related decreases in urea, total
protein and albumin were observed all of which were
statistically significant at 500 mg/kg/day and above.


No such changes were detected at the other dose levels.

Effects in organs:
Necroscopy:

No macroscopic abnormalities were detected at terminal kill.


Organ weights:

Animals of either sex treated with 1000 mg/kg/day showed an
increased liver weight, relative to bodyweight (18% in
males, 12% in females) and also absolute weight (24% in
males, 14% in females) when compared with controls. There
were no other changes considered toxicologically
significant.


Histopathology:

Microscopic examination of liver secretions revealed changes
identified as centrilobar hepatocyte enlargement for animals

of either sex treated with 1000 mg/kg/day and for one male
treated with 500 mg/kg/day.

Effect levels

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