Pyrazole

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Pyrazole

EC Number:

206-017-1

EC Name:

Pyrazole

Cas Number:

288-13-1

Molecular formula:

C3H4N2

IUPAC Name:

1H-pyrazole

Details on test material:

Purity 99.8%

Method

Target gene:

S. typhimurium: his-
E. coli: trp-

Species / strain

Species / strain / cell type:

bacteria, other: TA 1535, TA 100, TA 1537, TA 98 and E. coli WP2 uvrA

Metabolic activation:

with and without

Metabolic activation system:

S-9 mix from Aroclor 1254 induced rat liver homogenate

Test concentrations with justification for top dose:

20 ug - 5000 ug/plate (SPT and PIT; all strains)
20 ug - 8000 μg/plate (PIT; TA 1535)

Vehicle / solvent:

water

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

water

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene, N-methyl-N'-nitro-N-nitrosoguanidine, 4-nitro-o-phenylendiamine, 9-aminoacridine, N-ethyl-N'-nitro-N-nitrosoguanidine

Details on test system and experimental conditions:

METHOD OF APPLICATION: 1st experiment: standard plate test (SPT); 2nd experiment: preincubation test (PIT); 3rd experiment: high dose preincubation test (PIT) only with TA 1535

Evaluation criteria:

In general, a substance to be characterized as positive in the bacterial tests has to fulfill the following requirements :
- doubling of the spontaneous mutation rate (control)
- dose-response relationship
- reproducibility of the results

Results and discussion

Test results

Species / strain:

bacteria, other: TA 1535, TA 100, TA 1537, TA 98 and E. coli WP2 uvrA

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

No precipitation was found.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Standard plate test (20 - 5000 µg/plate)
Strain	Metabolic activation system	mean revertants in Controls	maximum revertant factor	dose dependency	Assessment
TA 98	no	27	1.0	no	negative
	yes	41	1.0	no	negative
TA 100	no	129	1.1	no	negative
	yes	142	1.1	no	negative
TA 1535	no	23	0.9	no	negative
	yes	23	1.0	no	negative
TA 1537	no	10	1.0	no	negative
	yes	10	1.1	no	negative
WP2 uvr A	no	33	1.0	no	negative
	yes	41	1.0	no	negative
Preincubation test (20 - 5000 µg/plate)
Strain	Metabolic activation system	mean revertants in Controls	maximum revertant factor	dose dependency	Assessment
TA 98	no	27	1.1	no	negative
	yes	47	1.0	no	negative
TA 100	no	122	1.2	no	negative
	yes	112	1.2	no	negative
TA 1535	no	18	2.0	yes	weakly positive
	yes	19	1.2	no	negative
TA 1537	no	12	1.0	no	negative
	yes	12	1.4	no	negative
WP2 uvr A	no	32	1.0	no	negative
	yes	39	1.2	no	negative
Preincubation test (2000 - 8000 µg/plate)
Strain	Metabolic activation system	mean revertants in Controls	maximum revertant factor	dose dependency	Assessment
TA 1535	no	19	2.6	no	weakly positive
	yes	21	1.6	no	negative

In the high dose PIT, the mean revertant factor in the 2000, 4000, 6000 and 8000 µg/plate treatments were 1.8, 2.6, 2.5 and 2.1, respectively. Therefore, no dose dependency was seen in this trial.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Regarding the results of the study, the test substance Pyrazole ist finally considered not to be mutagenic in bacteria. The weakly positive results in high doses were considered as caused by impurities.