Reaction mass of Benzenamine, N,N-dimethyl- , molybdate, tungstate & phosphates

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

25 March 1987 to 11 April 1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

Data is from study report

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

no strain to detect cross linking included

Principles of method if other than guideline:

Ames assay was performed to determine the mutagenic nature of test chemical.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

4-methyl-1-phenyl-3-pyrazolidone

EC Number:

220-180-6

EC Name:

4-methyl-1-phenyl-3-pyrazolidone

Cas Number:

2654-57-1

Molecular formula:

C10H12N2O

IUPAC Name:

4-methyl-1-phenylpyrazolidin-3-one

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (IUPAC name): 4-Methyl-1-phenyl-3-pyrazolidone- Common name: 4-Methyl-1-phenylpyrazolidin-3-one- Molecular formula: C10H12N2O- Molecular weight: 176.218 g/mol- Smiles notation: N1(NC(=O)[C@@H](C1)C)c1ccccc1 - InChl: 1S/C10H12N2O/c1-8-7-12(11-10(8)13)9-5-3-2-4-6-9/h2-6,8H,7H2,1H3,(H,11,13)- Substance type: Organic- Physical state: white powder

Method

Target gene:

histidine

Species / strain

Species / strain 1

Species / strain / cell type:

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

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 1538

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:

S-9 from aroclor 1254 induced rat livers

Test concentrations with justification for top dose:

dose range finding: 5, 50, 500 and 5000 ug/platemain assay (with independent repeat): 15, 50, 150, 500 and 1500 ug/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO - Justification for choice of solvent/vehicle: no data

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: aminoanthrocene

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium; in agar (plate incorporation)- Cell density at seeding (if applicable):ca 1E07/mLDURATION- Preincubation period: NA- Exposure duration: 72 hours at 37 °CNUMBER OF REPLICATIONS: 3/concentration (2 independent assays)DETERMINATION OF CYTOTOXICITY- Method:reduced bacterial back ground lawn and precipitate.

Rationale for test conditions:

No data

Evaluation criteria:

A test item is considered as mutagenic if:- a significant and dose-related increase in the number of revertants occurs with sufficient reproducibility- the number of revertant colonies is at least twice as high

Statistics:

NA

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at and above 5000 ug/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at and above 5000 ug/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Test results 3

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at and above 5000 ug/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Test results 4

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at and above 5000 ug/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Test results 5

Key result

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at and above 5000 ug/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS- Effects of pH: No data- Effects of osmolality: No data- Evaporation from medium: No data- Water solubility: No data- Precipitation: No data- Definition of acceptable cells for analysis: No data- Other confounding effects: No dataRANGE-FINDING/SCREENING STUDIES: dose range finding study was performed at dose levels of 5, 50, 500 and 5000 ug/plateCYTOKINESIS BLOCK (if used)- Distribution of mono-, bi- and multi-nucleated cells: No dataNUMBER OF CELLS WITH MICRONUCLEI- Number of cells for each treated and control culture: No data- Indication whether binucleate or mononucleate where appropriate: No dataHISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)- Positive historical control data: No data- Negative (solvent/vehicle) historical control data: No dataADDITIONAL INFORMATION ON CYTOTOXICITY:- Measurement of cytotoxicity used: No data- Other observations when applicable: No data

Remarks on result:

other: No mutagenic potential

Applicant's summary and conclusion

Conclusions:

Test chemical did not induce gene mutation in Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and TA1538 in the presence and absence of S9 metabolic activation system and hence it is not likely to be mutagenic in vitro.

Executive summary:

Ames assay was performed to determine the mutagenic nature of test chemical . The study was performed using Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and TA1538 in the presence and absence of aroclor 1254 induced S9 metabolic activation system in the standard plate incorporation assay. A dose range finding study was performed at dose levels of 5, 50, 500 and 5000 ug/plate. On the basis of the results obtained from the preliminary study, the test chemical was dissolved in DMSO and used at dose level of 15, 50, 150, 500 and 1500 ug/plate for the main study. In two independent assays with and without metabolic activation no increase of the number of revertants was observed. Based on the observations made, test chemical did not induce gene mutation in Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and TA1538 in the presence and absence of S9 metabolic activation system and hence it is not likely to be mutagenic in vitro.