3'-nitroacetophenone

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:

data from handbook or collection of data

Justification for type of information:

Data is from peer reviewed publication

Data source

Reference

Reference Type:

publication

Title:

Mutagenicity of mono-nitrobenzene derivatives in the Ames test and rec assay

Author:

Makoto Shimizu and Eiji Yano

Year:

1986

Bibliographic source:

Mutation Research, 170 (1986) 11-22

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

AMES Assay was performed to determine the mutagenic nature of m-Nitroacetophenone

GLP compliance:

no

Type of assay:

bacterial gene mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

3'-nitroacetophenone

EC Number:

204-504-3

EC Name:

3'-nitroacetophenone

Cas Number:

121-89-1

Molecular formula:

C8H7NO3

IUPAC Name:

3'-nitroacetophenone

Details on test material:

Name of test material (as cited in study report): 3 nitroacetophenone
Substance type: Organic
Physical state: Liquid
Purchased from : Kanto Chemicals, Co., Japan
Purity: 99%

Specific details on test material used for the study:

- Name of the test material: m-Nitroacetophenone
- EC name: 3'-nitroacetophenone
- Molecular formula: C8H7NO3
- Molecular Weight: 165.147 g/mol
- Substance type: Organic
- Purity: 99%
-Impurity: 1%

Method

Target gene:

Histidine

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA98, TA1538, TA1537, TA100, TA1535

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

No data

Metabolic activation:

with and without

Metabolic activation system:

S9 fraction was obtained from liver homogenate of male Sprague Dawley rats

Test concentrations with justification for top dose:

0, 0.1, 0.5, 1, 5 or 10 mg/plate

Vehicle / solvent:

- Solvent used: Sterilized DMSO
- Justification for choice of solvent/vehicle: The chemical was soluble in DMSO

Controls

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

N-ethyl-N-nitro-N-nitrosoguanidine

other: 2-aminoanthracene

Details on test system and experimental conditions:

METHOD OF APPLICATION: preincubation
- Cell density at seeding (if applicable): No data

DURATION
- Preincubation period: 15 mins
- Exposure duration: 70 hrs
- Expression time (cells in growth medium): 70 hrs
- Selection time (if incubation with a selection agent): No data
- Fixation time (start of exposure up to fixation or harvest of cells): No data

SELECTION AGENT (mutation assays): No data

SPINDLE INHIBITOR (cytogenetic assays): No data

STAIN (for cytogenetic assays): No data

NUMBER OF REPLICATIONS: All tests were performed in duplicate and repeated at least 3 times separately

METHODS OF SLIDE PREPARATION AND STAINING TECHNIQUE USED: No data

NUMBER OF CELLS EVALUATED: No data

NUMBER OF METAPHASE SPREADS ANALYSED PER DOSE (if in vitro cytogenicity study in mammalian cells): No data

CRITERIA FOR MICRONUCLEUS IDENTIFICATION: No data

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other: No data
- Any supplementary information relevant to cytotoxicity: The strains were observed for toxicity upon chemical treatment

OTHER EXAMINATIONS:
- Determination of polyploidy: No data
- Determination of endoreplication: No data
- Methods, such as kinetochore antibody binding, to characterize whether micronuclei contain whole or fragmented chromosomes (if applicable): No data

- OTHER: No data

Rationale for test conditions:

No data

Evaluation criteria:

Colonies of his+ revertants were counted after incubation, and chemicals inducing more than twice the number of revertant colonies on the control plate were considered as mutagenic.

Statistics:

The numbers of revertant colonies indicate mean ± S.D., all these numbers revertant colonies were counted after 68-72 h incubation

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA98, TA1538 and TA1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 10mg/plate

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

First the test were carried out without metabolic activation and was terminated if the mutagenicity was positive. In case of negative results, test with metabolic activation was carried out in addition.

Applicant's summary and conclusion

Conclusions:

m- nitroacetophenone failed to induce mutation in Salmonella typhimurium strain TA98, TA1538, TA1537, TA100, TA1535 in the presence and absence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.

Executive summary:

Gene mutation toxicity study was performed to determine the mutagenic nature of m- nitroacetophenone (EC name: 3'-nitroacetophenone). The study was performed using Salmonella typhimurium strain TA98, TA1538, TA1537, TA100, TA1535 in the presence and absence of S9 metabolic activation system at dose levels of 0, 0.1, 0.5, 1, 5 or 10 mg/plate by the preincubation assay. All tests were performed in duplicate and repeated at least 3 times separately. Concurrent solvent and postitive controls were included in the study. The plates were inverted and incubated at 37°C in dark for 70 h. First the tests were carried out without metabolic activation and were terminated if the mutagenicity was positive. In case of negative results, tests with metabolic activation were carried out in addition. Colonies of his+ revertants were counted after incubation, and chemicals inducing more than twice the number of revertant colonies on the control plate were considered as mutagenic. m- nitroacetophenone failed to induce doubling of mutation in Salmonella typhimurium strain TA98, TA1538, TA1537, TA100, TA1535 in the presence and absence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.