Solsperse 22000-Wirksubstanz

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

other: Body responsible for the test

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Annex V - method B.12

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Test animals

Species:

other: Mouse (C57BL/6JfBL 10/alpk)

Sex:

male/female

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

Corn oil

No. of animals per sex per dose:

Male: 3200 mg/kg; No. of animals: 5; Sacrifice time: 24 hoursMale: 5000 mg/kg; No. of animals: 5; Sacrifice time: 24 hoursMale: 5000 mg/kg; No. of animals: 5; Sacrifice time: 48 hoursMale: 5000 mg/kg; No. of animals: 5; Sacrifice time: 72 hoursFemale: 3200 mg/kg; No. of animals: 5; Sacrifice times: 24 hoursFemale: 5000 mg/kg; No. of animals: 5; Sacrifice times: 24 hoursFemale: 5000 mg/kg; No. of animals: 5; Sacrifice times: 48 hoursFemale: 5000 mg/kg; No. of animals: 5; Sacrifice times: 72 hours

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

reduced number of polychromatic erythrocytes

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

Observations:There was no observed increase in micronucleus formation

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negativeUnder the conditions of the test, the substance is not clastogenic in the mouse bone marrow micronucleus test

Executive summary:

The substance has been evaluated for its ability to induce micronucleated polychromatic erythrocytes in the bone marrow of C57BL/6JfBL10/Alpk mice. A single oral dose was given to groups of 5 male and 5 female mice at dose levels of 3200 and 5000 mg/kg, the higher dose being the limit dose for this assay. Bone marrow samples were taker 24 hours after dosing at 3200 mg/kg and 24, 48 and 72 hours after dosing at 500 mg/kg.

No statistically or biologically significant increase in the incidence of micronucleated polychromatic erythrocytes, over the vehicle control values, were seen at either dose level in males at any of the sampling times investigated. A small statistically significant increase was observed in females 48 hours after being dosed with the substance at 5000 mg/kg. This value is, however, within the concurrent vehicle control range and the statistical significance is considered to be due to a low female control value at 48 hour time point rather than to any effect of the substance. The increased observed is therefore considered to be of no biological significance. No such increase were observed at any other sampling time or dose level tested in the females.

The test system positive control, cyclophosohamide, induced statistically significant and biologically meaningful increase in mirconucleated polychromatic erythrocytes, compared to the vehicle control, thus demonstrating the sensitivity of the test system to a known clastogen.

Comparison of the percentage of polychromatic erythrocytes showed a statistically significant decrease, compared to the vehicle control value, in males 72 hours after being dosed at 5000 mg/kg. This indicates that the substance or one of its metabolites may have had a cytotoxic effect on the bone marrow resulting in a depression in the bone marrow proliferation.

It is therefore concluded that the substance, under the conditions of the test, is not clastogenic in mouce micronucleus test.