3-methyl-1-p-tolyl-5-pyrazolone

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: well performed GLP compliant study following a company guideline similar to OECD 471, but without confirmation of negative results ba follow up experiments

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: company guideline similar to OECD 471

Deviations:

yes

Principles of method if other than guideline:

as compared to current guideline without confirmation of negative results ba follow up experiments

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

3-methyl-1-p-tolyl-5-pyrazolone

EC Number:

201-708-4

EC Name:

3-methyl-1-p-tolyl-5-pyrazolone

Cas Number:

86-92-0

Molecular formula:

C11H12N2O

IUPAC Name:

3-methyl-1-p-tolyl-5-pyrazolone

Method

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 1538

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 induce rat liver S9-Mix

Test concentrations with justification for top dose:

Toxicity experiment and dose range finding: 0, 4, 20, 100, 500, 2500, 10000 µg/plate
Mutagenicity experiment: 0, 4, 20, 100, 500, 2500, 5000 µg/plate

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

N-ethyl-N-nitro-N-nitrosoguanidine

benzo(a)pyrene

other: 2-Aminoanthracene

Details on test system and experimental conditions:

METHOD OF APPLICATION: plate incorporation

DURATION

- Exposure duration: incubation for 48 to 72 hours at 37°C

NUMBER OF REPLICATIONS: triplicate plates per dose

DETERMINATION OF CYTOTOXICITY
- Method: A reduced rate of spontaneously occuring colonies as well as visible thinning of the bacterial lawn were used as indicator for toxicity.

Evaluation criteria:

criteria for a negative result: absence of a significant increase in the number of revertant colonies and of a dose dependent effect

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: slightly toxic to some of the bacterial strains

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: slightly toxic to some of the bacterial strains

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS

- Precipitation: no

RANGE-FINDING/SCREENING STUDIES:

- Toxicity and dose range finding experiments were performed

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

Summarizing, i t can be stated that the test item is not mutagenic in these bacterial test systems neither with nor without exogenous metabolic
activation at the dose levels investigated.

Findings do not meet criteria for classification according to Regulation (EC) No 1272/2008.

Executive summary:

The test substance was tested for mutagenicity with the strains TA 100, TA 1535, TA 1537, TA 1538, TA 98 of Salmonella typhimurium and Escherichia coli WP2uvrA.

The mutagenicity studies were conducted in the absence and in the presence of a metabolizing system derived from rat liver homogenate. A dose range of 6 different doses from 4 µg/plate to 5 000 µg/plate was used.

Control plates without mutagen showed that the number of spontaneous revertant colonies was similar to that described in the literature. All positive control compounds gave the expected increase in the number of revertant colonies.

Toxicity: The test compound proved to be slightly toxic to some of the bacterial strains, at 500 to 5 000 µg/plate. 5 000 µg/plate was chosen as top dose level for the mutagenicity study.

Mutagenicity: In the absence of the metabolic activation system the test compound did not show a dose dependent increase in the number of revertants in any of the bacterial strains. Also in the presence of a metabolic activation system, treatment of the cells with the test substance did not result in a relevant increases in the number of revertant colonies.