Registration Dossier

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

Reference
Name:
Unnamed
Type:
Constituent
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.