Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1998
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
See attachment
Limit test:
no

Test material

Test animals

Species:
rat
Strain:
CD-1
Sex:
male/female
Details on test animals or test system and environmental conditions:
Age : 26 - 30 days
Male weight: 72 - 78 g
Female weight: 70 - 83 g
Acclimatisation period: 8 days
Room temperature: 19 - 23°C
Relative humidity: 40 - 70 %

Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
other: 1% w/v methylcellulose in purified water
Duration of treatment / exposure:
Test duration: 28 days
Frequency of treatment:
Dosing regime: once a day
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

Examinations

Observations and examinations performed and frequency:
Clinical signs once a day
Neurobehavioural screening once a day
Body weight twice a week
Food consumption weekly
Water consumption daily
Sacrifice and pathology:
Clinical pathology: removal of blood samples, haematology, biochemistry
Terminal studies: organ weight, macroscopic pathology, microscopic pathology
Statistics:
Food consumption
body weight gain
organ weight
clinical pathology

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Details on results:
Clinical observations:
There were no deaths. Salivation, occurring immediately after dosing, was observed in the majority of male and female rats receiving 1000 mg/kg/day during the 4 week period. On isolated occasions among a few high dose level animals, salivation persisted for up to 30 minutes after dosing. Salivation was occasionally present in some animals receiving 150 mg/kg/day.

Brown perioral staining and wet coat, both associated with post dosing salivation, occurred infrequently among some high dose level animals during the 4 week treatment period.

Other findings consisted of paddling motions of the forepaws, which occurred frequently among both sexes treated with 1000 mg/kg/day. Walking on toes also occurred on occasions during the treatment period in females and, to a lesser extent among some males receiving 1000 mg/kg/day.
This finding persisted for up to 30 minutes after treatment.

Treatment with the test substance was not associated with any behavioural changes which were considered indicative of neurotoxicity.

Bodyweight gain, food and water consumption were all considered to have been unaffected by treatment with the test substance.

Laboratory findings:
Several biochemical and haematological parameters were slightly altered but values generally fell within historical control ranges. No findings of toxicological significance occured.

Effects in organs:
No treatment-related findings occured.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
> 1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Dose descriptor:
NOEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Classified as: Not classified under EU regulation