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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
repeated dose toxicity: oral, other
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From Jan. 1969 until 1971
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
The substance was administered orally by oral tube to rats of both sexes for 85 weeks (male) or 104 weeks (female). general conditions were checked every day. Food and water consumptions and body weight were measured once a week and recorded. Urinanalysis and hematological and pathological examinations were carried out three times (at 28 weeks, 56 weeks and end of test).
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Specific details on test material used for the study:
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: micronized
- Final preparation of a solid: suspension

Test animals

Species:
rat
Strain:
other: JCL-SD
Sex:
male/female
Details on test animals and environmental conditions:
no data available

Administration / exposure

Route of administration:
other: oral tube
Vehicle:
other: 1 g tragant per 100 ml distilled water
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
85 weeks (male); 104 weeks (female)
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Dose / conc.:
0.05 mg/kg bw/day (actual dose received)
Dose / conc.:
1.25 mg/kg bw/day (actual dose received)
Dose / conc.:
31.25 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
30
Control animals:
yes
Positive control:
no

Examinations

Observations and examinations performed and frequency:
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily

BODY WEIGHT: Yes
- Time schedule for examinations: once a week

FOOD CONSUMPTION: YES
- Time schedule for examinations: once a week
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Not specified
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Not specified

WATER CONSUMPTION: Yes
- Time schedule for examinations: once a wwek

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for examinations: at 28 weeks, 56 weeks and end of test (no further informnation available)

CLINICAL CHEMISTRY: Not specified

URINALYSIS: Yes
- Time schedule for examinations: at 28 weeks, 56 weeks and end of test (no further informnation available)

NEUROBEHAVIOURAL EXAMINATION: Not specified

IMMUNOLOGY: Not specified
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
- Time schedule for examinations: at 28 weeks, 56 weeks and end of test (no further informnation available)
HISTOPATHOLOGY: Yes
- Time schedule for examinations: at 28 weeks, 56 weeks and end of test (no further informnation available)
Statistics:
no data available

Results and discussion

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
ca. 1.25 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
clinical biochemistry
histopathology: non-neoplastic
Dose descriptor:
dose level:
Effect level:
31.25 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: depression of body weight gain, decrease of total cholesterol and atrophy of prostate, seminal vesicle and ovary
Remarks on result:
other: Effects observed after 56 weeks´treatment and end of the test

Target system / organ toxicity

Critical effects observed:
yes
Lowest effective dose / conc.:
31.25 mg/kg bw/day (actual dose received)
System:
other: male/female reproductive system
Organ:
seminal vesicle
ovary
other: prostate
Treatment related:
yes

Applicant's summary and conclusion

Executive summary:

The results show that the maximum non-effective dose of the test item in 85 weeks´(male) or 104 weeks´(female) oral administration was estimated at dose of slightly less than 1.25 mg/kg/day. The toxic effects recognized in rats of the highest dose group (31.25 mg/kg/day) are those generally found after administration of synthetic progestin hormones and not specific to the test item.