Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Body responsible for the test

Data source

Reference
Reference Type:
other: Body responsible for the test
Title:
Unnamed

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Deviations:
not specified
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Wistar (Han: WIST)
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Duration of treatment / exposure:
28 days
Frequency of treatment:
Dosing regime: 7 days/week
No. of animals per sex per dose:
Male: 10 animals at 0 mg/kg bw/day
Male: 5 animals at 40 mg/kg bw/day
Male: 5 animals at 200 mg/kg bw/day
Male: 10 animals at 1000 mg/kg bw/day
Female: 10 animals at 0 mg/kg bw/day
Female: 5 animals at 40 mg/kg bw/day
Female: 5 animals at 200 mg/kg bw/day
Female: 10 animals at 1000 mg/kg bw/day

Results and discussion

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
40 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day
Dose descriptor:
NOEL
Effect level:
40 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

Any other information on results incl. tables

Clinical observations:

In the intermediate and high dose group dose dependend an increased salivation was observed.

The animals of the high dose group showed bright feces from the second week and at the end of the treatment reduced activity, skin turgor and righting reflex. Two females of the high dose group did not show the ear reflex.

The discolouration of the feces was seen in the discovery group till the end of the first week of the recovery period. One male of the low dose group showed a reduced righting reflex at day 15. At the examination on day 26 a reduced righting reflex was observed at one male of the intermediate dose and at two male of the low dose group.

In the males of the high dose group a reduced body weight development was measured at the end of the study. The food consumption of these animals was reduced during the whole application period, in the females of the high dose group a reduced food consumption was observed during the first two weeks of the treatment.

Laboratory findings:

Haematology: In the females of the intermediate and high dose group an increase of the number of thrombocytes and an

enlargement of the prothrombin time in the males in all dose groups (without relation to the doses) and in females of high and low dose group was observed.

Clinical chemistry: In females of the high dose group the values for giucose and triglycerides were increased and in both sexes the protein values were reduced. In the males of the high dose group increased activities for ALAT was determined.

Effects in organs:

On the animal body white areas and redness of the mucosa of the stomach and a swelling of the duodenum septum in all animals of the high dose groups were seen. One animal of the intermedium dose group showed a swollen duodenum too.

Microscopically in the animals of the intermedium and high dose group a hyperplasy of the mucousa in the duodenum was

detected. In the recovery groups no treatment related changes were observed.

Applicant's summary and conclusion

Conclusions:
not classified