1H-Indole-3-acetic acid, 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-, 2-(1,1-dimethylethoxy)-2-oxoethyl ester

Acute Toxicity: dermal

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

Test material information

Constituent 1

Reference substance name:

2-(tert-butoxy)-2-oxoethyl 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetate

EC Number:

616-210-6

Cas Number:

75302-98-6

Molecular formula:

C25 H26 Cl N O6

IUPAC Name:

2-(tert-butoxy)-2-oxoethyl 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetate

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 levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

1 451 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 100 - < 500 mg/kg bw

Based on:

test mat.

Effect levels 3

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.