Registration Dossier

Toxicological information

Repeated dose toxicity: oral

Currently viewing:

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Deviations:
no
GLP compliance:
yes
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Bor:WISW (SPFCpb)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann Versuchstierzucht GmbH & Co.KG
- Age at study initiation: males 7 weeks; females 8 weeks
- Weight at study initiation: males 145 - 195 g; females 135 - 166 g
- Housing: individually in Macolon cages, type II
- Diet (e.g. ad libitum): standart diet ad libitum
- Water (e.g. ad libitum):drinking water ad libitum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 (for short periods up to 25)
- Humidity (%): 40-70 (for short periods up to 80)
- Photoperiod: 6 a.m. - 6 p.m. CET artificial lighting; 6 p.m. - 6 a.m. CET natural light-dark-rhythm

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS:
daily preparation of the solutions for administration with different substance concentrations according to the intended doses
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
The concentration of the test substance was determined in aqueous samples at the beginning and at the end of the study by HPLC.
Duration of treatment / exposure:
28 days
Frequency of treatment:
once daily
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0 mg/kg bw
Basis:
nominal in water
Remarks:
Doses / Concentrations:
215 mg/kg bw
Basis:
nominal in water
Remarks:
Doses / Concentrations:
1000 mg/kg bw/day
Basis:
nominal in water
No. of animals per sex per dose:
0 mg/kg bw/say: 10 male + 10 female animals; 5 animals of each sex were used as recovery animals
215 mg/kg bw/say: 5 male + 5 female animals
1000 mg/kg bw/say: 10 male + 10 female animals; 5 animals of each sex were used as recovery animals
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: doses were selected on the basis of a previous dose finding study
- Rationale for animal assignment: Rats were used according to international recommendations.
- Post-exposure recovery period in satellite groups: 6 weeks
Positive control:
no

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule:
occurence of toxicity symptoms: daily
mortality: twice daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule:
reflexes: once a week, starting with pretest period
examination of eyes, hearing and teeth: prior to first substance administration and in test week 4

BODY WEIGHT: Yes
- Time schedule for examinations: once a week, starting with pretest period

FOOD CONSUMPTION: Yes

HAEMATOLOGY: Yes
- Time schedule for collection of blood: test week 4
- How many animals: all animals

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: test week 4
- How many animals: all animals

URINALYSIS: Yes
- Time schedule for collection of urine: test week 4
Sacrifice and pathology:
GROSS PATHOLOGY: Yes

HISTOPATHOLOGY: Yes
Statistics:
For food consumption, body weights, and organ weights the DUNNETT-Test was used.
For values of hematological and clinical chemistry examinations the DUNNET-Test was used in case of normal distribution, otherwise the STEEL-Test was employed.

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 specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not specified
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:
not specified
Details on results:
ORGAN WEIGHTS
Absolute organ weights showed no significant differences. In relative organ weights minimal alterations of statistical significance in the weight of kidneys (left, decrease in low dose males week 5, slight increase in high dose females week 5) and testes (left, high dose males week 11) were recorded, but these marginal variations are well within the normal range of the species and they are considered to be incidental findings.

Effect levels

Dose descriptor:
NOEL
Effect level:
> 1 000 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: overall effects

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The administration of 215 and 1000 mg/kg test substance resulted in no observable effects. Therefore the NOEL (no observed effect level) is considered to be >1000 mg/kg bw in the rat.