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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2003
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))
Version / remarks:
OECD 424
GLP compliance:
yes (incl. QA statement)
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Age/Weight at start: 6-week old; 202-233g (males) and 159-189g (females)
- Temp.: 22+/-2°C; RH: 30-70%; light/dark cycle: 12h/12h; ventilation: 12 cycles/h
- Housing: 1/cage ; food and water ad libitum except when fasting required

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% MC (methylcellulose) in water
Details on oral exposure:
- gavage using plastic syringe fitted with a metal probe
- dose-volume = 5ml/kg, adjusted to the most recent body weight
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
- Homogeneity and stability: checked at 2 and 200 mg/mL, before the study start
- Control of preparations: all concentrations including controls in weeks 1 and 4

0 (Vehicle control).
Duration of treatment / exposure:
29 days
Frequency of treatment:
once a day
Doses / concentrations
Remarks:
Doses / Concentrations:
0 (vehicle controls) – 150 – 450 - 1000 mg/kg
Basis:
other: 0 (vehicle controls) – 150 – 450 - 1000 mg/kg
No. of animals per sex per dose:
5
Control animals:
yes
Positive control:
None.

Examinations

Observations and examinations performed and frequency:
- Mortality/morbidity, Clinical signs : daily; Detailed clinical observation : weekly
- Functional Observation Battery (FOB): Once (end of dosing period)
- Body weight/Feed Intake: weekly
- Haematology (incl. coagulation) and blood biochemistry: Once (end of dosing period)
Sacrifice and pathology:
- Organ weights and macroscopic examination: all animals
- Microscopic examination: all tssues for control and high dose rats and any gross lesion
Statistics:
Yes (decision tree, according to distribution of data) for: Body weight , food intake, haematology, blood biochemistry and organ weights

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
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed

Effect levels

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (actual dose received)
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Observations

Clinical signs and mortality

No deaths and no clinical signs at any dose. 

Body weight and weight gain

no effects

Food consumption and compound intake (if feeding study)

No effects at any dose

Food efficiency

not applicable

Water consumption and compound intake (if drinking water study)

not applicable 

Ophthalmoscopic examination

Not performed

Haematology

No relevant effects at any dose 

Clinical chemistry

No relevant effects at any dose 

Urinalysis

 Not performed 

Neurobehaviour

No CNS effects according to FOB resultsat any dose 

Organ weights

No relevant effects at any dose 

Gross pathology

No major macroscopic observationsat any dose

Histopathology: non-neoplastic

No toxicologically relevant observations 

Histopathology: neoplastic

 Not applicable 

Applicant's summary and conclusion

Conclusions:
No overt toxicity after 4 week of oral dosing at 1000 mg/kg/day.
NOAEL = 1000 mg/kg/day po