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

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline GLP 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:

The point-mutagenic effects were investigated in doses up to 12500 µg/plate on four histidine-auxotropic Salmonella typhimurium LT2 strains, for each substance, dose level and strain 4 plates were used. After an incubation period of 48 h the number of revertant colonies per plate were counted.

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

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, white powder, content 99.3%

Method

Target gene:

histidin gene locus

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA 1535, TA 100, TA 1537, TA 98

Metabolic activation:

with and without

Metabolic activation system:

rat liver homogenate (S-9 mix)

Test concentrations with justification for top dose:

Acemetacin-tert.-butylester: 20-12500 µg/plate in the first trial and 375-12000 µg/plate in the second trial
Sodium azide: 10 µg/plate (TA 1535)
Nitrofurantoin: 0.2 µg/plate (TA 100)
4-Nitro-o-phenylendiamin: 10 µg/plate (TA 1537) and 0.5 µg/plate (TA 98)
2-Aminoanthracene: 3 µg/plate

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

no

Remarks:

No solvent control was used since sufficient evidence was available in the literature and from testing laboratory experience, indicating that the solvents used had no influence on the spontaneous mutant counts of the used strains.

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: Sodium azide (TA 1535, without S9-mix), Nitrofurantoin (TA 100, without S9-mix), 4-Nitro-o-phenylendiamin (TA 1537 and 98, without S9-mix), 2-Aminoanthracene (with S9-mix)

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA 1535, TA 100, TA 1537, TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Remarks:

at 2500 µg/plate and above substance precipitation could be observed; therefore, evaluation of 12500 µg/plate was only possible to a limit extent

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Executive summary:

Acemetacin-tert.-butylester was tested in the Salmonella/microsome test for point-mutagenic effects in doses up to 12500 µg/plate on the four histidine-auxotrophic Salmonella typhimurium LT2 strains TA 1535, TA 100, TA 1537 and TA 98.

No bacteriotoxic effects was seen, but at 2500 µg/plate and above substance precipitation could be observed. Therefore, the evaluation of 12500 µg/plate was only possible to a limit extent.

No evidence for a mutagenic activity of Acemetacin-tert.-butylester was found.