Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Butindiol
- Analytical purity: 99.5 %

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRK,CH-4414 Füllinsdorf
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: males: 38.8 g/ females: 30.7 g
- Housing: single; Cage type Markolon Type I.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 3°C
- Humidity (%): 22 - 70 %
- Photoperiod (hrs dark / hrs light): 12 hours

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
- Vehicle: deionised water
Duration of treatment / exposure:
24/48 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
17.5; 35; 70 mg/kg
Basis:

No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Positive control(s):
30 mg/kg b.w. cyclophosphamide

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

Ten animals (5 males, 5 females) per test group were evaluated for the occurrence of micronuclei .

2000 polychromatic erythrocytes (PCE) per animal were scored for micronuclei.

To describe a cytotoxic effect due to the treatment with the test article the ratio between polychromatic and normochromatic erythrocytes (NCE) was determined in the same sample and reported as the number of NCEs per 2000 PCEs.

The following dose levels of the test article were investigated:

24 h preparation interval: 17.5, 35 and 70 mg/kg b.w.

48 h preparation interval: 70 mg/kg b.w.

The highest dose applied (70 mg/kg b.w.) was estimated by pre-experiments to be close to the maximum tolerated dose. The animals expressed toxic reactions.

After treatment with the test article the number of NCEs was not increased as compared to the corresponding vehicle controls thus indicating that BUTINDIOL had no cytotoxic effectiveness in the bone marrow.

In comparison to the corresponding vehicle controls there was no significant or biologically relevant enhancement in the frequency of the detected micronuclei at any preparation interval after administration of the test article and with any dose level used.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
In conclusion, it can be stated that during the study described and under the experimental conditions reported, the test article did not induce micronuclei as determined by the micronucleus test with bone marrow cells of the mouse. Therefore, BUTINDIOL is considered to be non-mutagenic in this micronucleus assay.