Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08.2007 to 01.2008
Reliability:
1 (reliable without restriction)
Cross-reference
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
according to guidelines

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
according to guideline
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
HPLC
Duration of treatment / exposure:
28 days
Frequency of treatment:
daily; 7 days/week for 4 weeks;
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
50 mg/kg body weight/day
Basis:
actual ingested
Remarks:
Doses / Concentrations:
200 mg/kg body weight/day
Basis:
actual ingested
Remarks:
Doses / Concentrations:
1000 mg/kg body weight/day
Basis:
actual ingested
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Details on study design:
Doses are based on dose-range-finding

Examinations

Observations and examinations performed and frequency:
Viability/Mortality, General Cageside Observations/ Detailed Clinical Observations (weekly), Grip strenght, Locomotor activity, food consumption, body weight, hematology, clinical biochemistry, urinalysis, organ weight, macroscopic findings, microscopic findings.

Sacrifice and pathology:
HISTOPATHOLOGY: Yes
Gross Pathology: yes
Statistics:
Dunnett-test
Steel-test
Fisher`s exact-test
Armitage/Cochran Trend Test

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:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
effects observed, treatment-related
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
One animal (male, 50 mg/kg(day) died spontaneously on treatment day 5. This spontaneously death was not considered to be test-related.

No test item-related clinical signs were observed.

Inreased locomotor activity in both sexes at 1000 mg/kg/day.

Absolute and relative food consumption and body weight was not influenced by the treatment during the treatment and recovery period.

No test item-related alterations in the mean fore- and handlimb grip strenght were recorded in rats at any dose levels.
No test item-related findings in hematology were recorded.

No test item-related changes in clinical biochemistry and urinalysis.

Increased mean thymus/body weight ratio and mean thymus/brain weight ratio was recorded in males at 1000 mg/kg/day at the end of the recovery period. As there were no histopathological correlates this finding was considered to be incidental. No further findings were recorded.

No test item-related macroscopic lesions were observed.

Minimal hypertrophy of the zona fasciculata was recorded in male animals and slight hypertrophy of the zona fasciculata in one female. Minimal hypertrophy of the zona glomerulosa in one male animal.
Minimal increased erythropoiesis was recorded in female animals; after a 14-day-treatment-free recovery period none of these changes were present

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
> 200 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
other: Increased locomotor activity in both sexes at 1000 mg/kg/day
Remarks on result:
not measured/tested
Remarks:
Effect level not specified (migrated information)

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
not subject of classification and labeling