Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

Principles of method if other than guideline:
Single administration of six concentrations with an application volume of 10 ml/kg to fasted rats (5 males and 5 females) via stomach tube with an observation period of 14 days.
GLP compliance:
yes
Remarks:
the study was not planned as GLP-study but was conducted according to the GLP-principles; deviation: the experimental procedure was not inspected by QA
Test type:
other: acute oral toxicity, rat
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Acemetacin-tert.-butylester, solid yellow powder

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
peanut oil
Doses:
25, 50, 100, 160, 180 and 200 mg/kg
No. of animals per sex per dose:
5
Control animals:
no

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
67 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 25 - < 50 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
36 mg/kg bw
Based on:
test mat.

Any other information on results incl. tables

Clinical signs at 50 mg/kg and above included piloerection, nasal discharge, bloody muzzle, increased salivation, paleness, sunken flanks, sedation, laboured breathing and emaciation. Onset of symptoms was 1 h after administration, on day 13 signs had disappeared.

No symptoms occurred in males after dosage with 25 mg/kg. One female showed slight to moderate salivation lasting about 1 day after administration and ruffled fur.

The surviving animals of the 50 mg/kg dose group showed a significant reduction of body weight during the first week.

Death occurred from day 2 until day 9. Necropsy of dead animals showed findings including abdominal cavity filled with serous liquid, abdominal organs with multiple adhesions and fibrinoid coatings. No findings were observed at final necropsy.

Applicant's summary and conclusion

Executive summary:

The acute oral toxicity of Acemetacin-tert.-butylester was determined in male and female rats after single administration of six concentrations with an application volume of 10 ml/kg via stomach tube with an observation period of 14 d.

The acute oral LD50 for males was 67 mg/kg and for females > 25 < 50 mg/kg. The LD50 for both sexes is approximately 36 mg/kg.