1H-Pyrazole-5-carboxylic acid, 3-(chloromethyl)-1-(3-chloro-2-pyridinyl)-, methyl ester

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: GLP study according EU/OECD guideline.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

(1997)

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

methyl 3-(chloromethyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylate

EC Number:

936-879-0

Cas Number:

1247712-63-5

Molecular formula:

C11H9Cl2N3O2

IUPAC Name:

methyl 3-(chloromethyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylate

Method

Species / strain

Species / strain 1

Species / strain / cell type:

E. coli WP2 uvr A

Species / strain 2

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

S9-mix

Test concentrations with justification for top dose:

The following doses per plate were evaluated:
test substance 5, 15.81, 50, 158.1, 500, 1581, 5000 μg per plate

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 4-nitro-1,2-phenylenediamine (TA 98), Sodium azide (TA 100, TA 1535), 9-aminoacridine (TA 1537), Methyl-methanesulfonate (E.coli WP2 uvrA), 2-aminoanthracene (TA 98, TA 100, TA 1535, TA 1537, E.coli WP2 uvrA, +S9-mix)

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

positive

Remarks:

with and without S9-mix

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 1581 and 5000 µg/plate (without S9-mix)

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 2

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 5000 µg/plate (without S9-mix)

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium, other: TA 98, TA 1535, TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 1581 and 5000 µg/plate for TA 98 and TA 1537 (without S9-mix) and at 5000 µg/plate for TA 1535 (without S9-mix)

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

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):
positive

The Salmonella/microsome test, employing doses of up to 5000 ug/plate, showed the test substance does produce bacteriotoxic effects at concentrations of 1581 and 5000 µg/plate for TA 98, TA 100 and TA 1537 (without S9-mix) and at 5000 µg/plate for TA 1535 and E.coli uvr A (without S9-mix). In experiment I using the plate incorporation method as well as in experiment II (pre-incubation method), a weak positive effect of the test item was obtained as the observed revertant colony numbers were above the respective biological threshold value in one tested bacterial strain (Salmonella typhimurium TA100 strain with and/or without metabolic activation). The effect was considered to be dose-related, reproducible and biologically relevant. No indications of mutagenic effects of the test substance could be found at assessable doses of up to 5000 ug/plate in any of the other Salmonella typhimurium (TA 98, TA 1535 and TA 1537) and E.coli WP2 uvr A strains used. In conclusion, the test item had weak mutagenic activity in one of the bacterium tester strains (TA 100) under the test conditions used in this study.