Registration Dossier

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
Study period:
2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline conform, GLP study
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
no
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals and environmental conditions:
according guideline

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
30% DMSO/70% PEG 400
Details on exposure:
substance formulated in vehicle
Duration of treatment / exposure:
animals received the test item once
Frequency of treatment:
once
Post exposure period:
24 h, 48 h
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
2000 mg/kg body weight
Basis:
actual ingested
Remarks:
Doses / Concentrations:
1000 mg /Kg body weight
Basis:
actual ingested
Remarks:
Doses / Concentrations:
500 mg/kg body weight
Basis:
actual ingested
No. of animals per sex per dose:
low dose: 6 females, 6 males
medium dose: 6 females, 6 males
main experiment: 12 females, 12 males
Control animals:
yes, concurrent vehicle
Positive control(s):
Cyclophosphamide, 40 mg/kg b.w; 24 h;

Examinations

Tissues and cell types examined:
bone marrow cells; polychromatic erythrocytes; normochromatic erythrocytes
Details of tissue and slide preparation:
according guideline
Evaluation criteria:
standard
Statistics:
nonparametric Mann-Whitney test

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Remarks:
ruffeled fur within 4 h after treatment with 2000 mg/kg b.w.
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
pre-expirement:
4 animals (2 males, 2 females) treated with 100 mg/kg b.w. did not express any toxic reactions;
4 animals (2 males, 2 females) treated with 1000 mg/kg b.w: : 1 male and 1 female had ruffeled fur within 2 and 6 h;
4 animals (2 males, 2 females) treated with 2000 mg/kg b.w: :2 males, 1 female had ruffeled fur 1 h post-treatment and 2 males and 2 females within 2 and 24 h post-treatment;

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
The oral application of the substance to mice did not induce increased micronucleated polychromatic erythrocytes in bone marrow.
Executive summary:

The test substance was investigated for its micronuclei formation potential in bone marrow in mice. Each 12 males and 12 females received by gavage single applications at dose levels up to 20000 mg/kg bw. After 1 h 5 males and 7 females expressed toxic reactions by ruffeled fur; after 2 -4 h 3 males and 4 females had ruffeled fur. The ratios of polychromatic erythrocytes to normochromatic erythrocyte were not affected by the treatment. No increase of micronuclei formation was observed for treated animals.