N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-3-oxobutyramide

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:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Important aspects (4 plates per dose, exposure concentrations, tester strains) in line with current OECD guidelines, but study design is restricted, because no confirmation of negative results by follow up experiments was provided. Study was performed prior to implementation of GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: company guideline similar to OECD 471

Deviations:

not applicable

Principles of method if other than guideline:

1) Ames, B.N. et al. (1973) "Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection." Proceedings of the National Academy of Sciences 70, 2281-2285
2) Green, M.H.L. and Muriel, W.J. (1976) "Mutagen testing using TRP+ reversion of Eschirichia coli." Mutation Research 38, 2-32

GLP compliance:

no

Remarks:

- performed prior to GLP implementation

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-3-oxobutyramide

EC Number:

247-820-7

EC Name:

N-(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)-3-oxobutyramide

Cas Number:

26576-46-5

Molecular formula:

C11H11N3O3

IUPAC Name:

3-oxo-N-(2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)butanamide

Details on test material:

- Name of test material (as cited in study report): Acetolon (Code: 336 / 80)

Method

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 1538

Species / strain 3

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

S9 liver homogenate

Test concentrations with justification for top dose:

4, 20, 100, 500, 2500, 10000 µg/plate

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 9-Aminoacridine, 2-Aminoanthracene, Methylhydrazone Derivative, Streptocotocin, ENNG

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

INCUBATION: Plates were incubated upside down at 37°C for two days, after which the number of revertant colonies was counted.

NUMBER OF REPLICATIONS: quadruplicate plating

Evaluation criteria:

A chemical is considered to have a positive response if the number of induced revertantes is more than double the spontaneous mutations.

Results and discussion

Test results

Species / strain:

other: S. typhymurium TA 98, TA 100, TA 1535, TA1537, TA 1538, E. coli WP2 uvrA

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, the test item did not induce gene mutations in any tester strain with and without metabolic activation.

Executive summary:

The test substance was examined in the mutagenicity test in bacteria first described by Ames and co-workers and acording to a company guideline. Under the conditions employed the test substance showed no mutagenic activity at dose ranges from 4µg to 10000µg per plate.