Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
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:
1987
Report date:
1987

Materials and methods

Principles of method if other than guideline:
Single administration of four concentrations, occlusively applied to the intact clipped skin for an exposure period of 24 hours and an observation period of 14 days.
GLP compliance:
no
Remarks:
GLP-like, deviations: the experimental procedure was not inspected by QA, stability of the test substance in the application formulation was not analytically examined
Test type:
other: acute dermal toxicity
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Acemetacin-tert.-butylester, solid yellow powder, purity 97%

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: Cremophor EL
Duration of exposure:
24 h
Doses:
100, 500, 1000 and 2000 mg/kg
No. of animals per sex per dose:
5

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
1 451 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 100 - < 500 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
918 mg/kg bw
Based on:
test mat.
95% CL:
462 - 1 829

Any other information on results incl. tables

At 2000 mg/kg local inflammation was seen at the application site.

Clinical signs at 500 mg/kg and/or above included piloerection, palor, sedation, sunken flanks, nasal discharge, bloody muzzle, and increased salivation. Onset of symptoms was 1 h post administration, on day 13 all survivors were free of signs.

Death occurred from day 5 until day 10 after administration. Necropsy of dead animals showed peritonitis with proliferations and fibrinously coated abdominal organs. In some animals the abdominal cavity and the thoracic cavity were filled with serous fluid.

At final necropsy small intestined adhered to the peritoneum in a 2000 mg/kg female, all other survivors showed no pathological changes.

Applicant's summary and conclusion

Executive summary:

The acute dermal toxicity of Acemetacin-tert.-butylester was determined in male and female rats after single administration of four concentrations occlusively to intact clipped skin with an exposure period of 24 h and an observation period of 14 d.

The acute derml LD50for males was 1451 mg/kg and for females > 100 < 500 mg/kg. The LD50for both sexes is 918 mg/kg.