Reaction mass of 3-(difluoromethyl)-1-methyl-N-[(1RS,4SR,9RS)-1,2,3,4-tetrahydro-9-isopropyl-1,4-methanonaphthalen-5-yl]pyrazole-4-carboxamide and of 3-(difluoromethyl)-1-methyl-N-[(1RS,4SR,9SR)-1,2,3,4-tetrahydro-9-isopropyl-1,4-methanonaphthalen-5-yl]pyrazole-4-carboxamide; isopyrazam

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

15 May 2006 to 20 Jun 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Version / remarks:

1997

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)

Version / remarks:

2000

GLP compliance:

yes (incl. QA statement)

Type of assay:

mammalian erythrocyte micronucleus test

Test material

Test material information

Constituent 1

Reference substance name:

632-619-2

EC Number:

632-619-2

Cas Number:

881685-58-1

Molecular formula:

C20 H23 F2 N3 O

IUPAC Name:

632-619-2

Test animals

Species:

rat

Strain:

Wistar

Remarks:

HsdRCCHan

Sex:

male

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

0.5 % w/v aqueous carboxymethylcellulose (CMC)

Doses / concentrations

Dose / conc.:

2 000 mg/kg bw/day

Control animals:

yes, concurrent vehicle

Positive control(s):

Cyclophosphamide

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

not examined

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

Micronucleus Test

The test material was tested at the limit dose of 2000mg/kg. No significant increases in the incidence of micronucleated immature erythrocytes, compared to the vehicle control values, were seen in any treated rats at either of the sampling times investigated. The sensitivity of the test system was clearly demonstrated by the marked increases in the frequencies of micronucleated immature erythrocytes induced by the positive control substance, cyclophosphamide. The data from the study do not indicate any clastogenic activity of the test material in the rat bone marrow when tested up to 2000 mg/kg, the limit dose.

Applicant's summary and conclusion

Conclusions:

Under the conditions of test, the test material is not clastogenic in the rat bone marrow micronucleus test.

Executive summary:

The test material has been evaluated for its ability to induce micronucleated immature erythrocytes in the bone marrow of HsdRCCHan: WIST rats in a study according to OECD TG 474 following GLP principles. A single oral dose was given to groups of male rats at a dose level of 2000 mg/kg. This dose level is the limit dose level of the assay. Bone marrow samples were taken 24 and 48 hours after dosing.

No significant increases in the incidence of micronucleated immature erythrocytes, over the vehicle control values, were seen at either of the sampling times investigated. Comparison of the percentage of immature erythrocytes showed no significant differences at either of the sampling times between the vehicle control animals and those treated with the test material. The test system positive control, cyclophosphamide, induced biologically meaningful increases in

micronucleated immature erythrocytes, compared to the vehicle control values, thus demonstrating the sensitivity of the test system to a known clastogen.

Under the conditions of test, the test material is not clastogenic in the rat bone marrow micronucleus test.