1H-Pyrazole, 1,4-dimethyl-

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

OECD 471, negative (Nissan Chemical Industries, LTD, 1994)

Link to relevant study records

Reference

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other: GLP compliant, similar to guideline study, available as unpublished report, adequate for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Target gene:

- S. typhimurium: His-locus
- E.coli: Trp-locus

Species / strain / cell type:

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

Additional strain / cell type characteristics:

not applicable

Species / strain / cell type:

E. coli WP2 uvr A

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Liver S9 fraction of phenobarbitone and ß-naphthoflavone induced rats

Test concentrations with justification for top dose:

Pre-test: 100, 500, 1000, 2000, 5000 µg/plate
Main test: 313, 625, 1250, 2500, 5000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: distilled water

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

other: 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide; 2-Methoxy-6-chloro-9-(3-(2-chloroethyl)-amionpropylamino)acridine 2HCl; 2-aminoanthracene

Remarks:

With metabolic activation: 2-AA (all strains); Without metabolic activation: 2-(2-Furyl)3-(5-nitro-2-furyl)acrylamide (TA 98, TA 100, WPr2 uvrA), sodium azide (TA 1535), 2-Methoxy-6-chloro-9-(3-(2-chloroethyl)-amionpropylamino)acridine 2HCl (TA 1537)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION : Exposure duration: 48 hours

NUMBER OF REPLICATIONS: 2 test plates per dose or control

DETERMINATION OF CYTOTOXICITY: growth inhibition

Evaluation criteria:

The main test was valid when the sterility test confirmed the absence of bacterial contamination and when the number of revertant colonies both for the solvent and positive controls was within the range of the background data. Then, the test substance was judged positive when the number of revertant colonies (mean value of two plates) was more than twice that of the solvent control and dose-related. When judgement the reproducibility for the test result was confirmed between a range-finding test and a main test.

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results (migrated information):
negative

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

in vitro

A bacterial reverse mutation assay was conducted in accordance with OECD 471 and in compliance with GLP. Salmonella typhimurium strains TA 1535, 1537, 98, 100, and E. coli WP2 uvrA were exposed 0, 313, 625, 1250, 2500, and 5000 µg/plate in a Standard Plate Test. Solvent and positive controls were also tested. The tests were conducted with and without metabolic activation (S9 fraction of phenobarbitone and ß-naphthoflavone induced rats). No bacteriotoxic effects were observed. An increase in the number of his+ or trp+ revertants was not observed in the standard plate test without S9 mix or after the addition of a metabolizing system. Therefore, under the condition of this study the test substance is considered not to be mutagenic.

Justification for selection of genetic toxicity endpoint
only study available

Justification for classification or non-classification

Based on the available information the substance is not classified for genetic toxicity in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.