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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
GLP compliance:
yes
Limit test:
no

Test animals

Species:
other: rat, Sprague-Dawley

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
other: Arachis oil BP
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:
Mortality Data:


One male treated with 1000mg/kg/day was found dead at the
start of Day 5 as a result of a mal-dose.


There were no other unscheduled deaths.


Clinical Observations:


One male treated with 1000mg/kg/day developed clinical signs
prior to dosing from Day 2 including hunched posture,
pilo-erection, dehydration, wet fur and red/brown staining
around the eyes, probably resulting from a mal-dose on the
previous day. This animal was subsequently found dead at the
start of Day 5.


Increased salivation was detected immediately after dosing
in the remaining 1000mg/kg/day animals from day 3 onwards
but such observations are often reported when a test
material formulation has an unpleasant taste or is slightly
irritant and, in isolation, are considered not to be
indicative of toxicity.


No such clinical signs were detected in animals treated with
150 or 15mg/kg/day throughout the study period.


Bodyweight:


Females treated with 1000mg/kg/day showed a slight reduction
in bodyweight gain during Week 2 of the study.


Bodyweight development for 1000mg/kg/day males and for
animals of either sex treated with 150 or 15mg/kg/day was
similar to that of controls throughout the study.



Food Consumption:


A slight reduction in dietry intake was detected for
1000mg/kg/day females during Week 2.


No adverse effect on dietry intake was detected for
1000mg/kg/day males or for animals of either sex from the
remaining dose groups.


Water Consumption:


No intergroup differences were detected.

Laboratory findings:
Haematology:


No treatment-related effects were detected.


Blood Chemistry:


No treatment-related effects were detected.

Effects in organs:
Necropsy:


The decedent from the 1000mg/kg/day showed normal post
mortem changes together with changes consistent with a
mal-dose.


No treatment-related macroscopic abnormalities were detected
in 150 or 15mg/kg/day animals at terminal kill.


Organ Weights:


Dose-related increase in absolute weight for heart and
kidney were observed which reached 40 and 21% respectively
above controls.


For relatative heart and kidney weight the dose-response
relationship was less strong, but high dose animals showed
an increase of 34 and 13% respectively compared to controls.

The increase in absolute heart and kidney weight observed at
15 and 150 mg/kg/day althought dose-related were small and
not considered toxicologcally significant.


No such increases were detected for females.

Histopathology:


No treatment-related microscopic abnormalities were
detected.

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

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