Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Type of information:
experimental study
Adequacy of study:
key study
Study period:
27 August 2013 to 16 October 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
yes
Remarks:
On occassions the relative humidity was outside the target range of 30-70%. The animals in the main test, with the exception of the positive control group were housed in groups of seven.
GLP compliance:
yes
Type of assay:
other: Mammalian Erythrocyte Micronucleus Test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: pale yellow solid block
Details on test material:
- Name of test material (as cited in study report): Dantocol DHE
- Physical state: pale yellow solid block
- Lot/batch No.: M5469330
- Storage condition of test material: room temperature in the dark

Test animals

Species:
mouse
Strain:
ICR
Details on species / strain selection:
Sufficient albino Hsd: ICR (CD-1)
Sex:
male/female

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
Phoshate Buffered Saline (PBS)
Duration of treatment / exposure:
Once.
Frequency of treatment:
Once.
Post exposure period:
24 hours (500, 1000 or 2000 mg/kg bw) and 48 hours (2000 mg/kg bw group) post-treatment.
Doses / concentrationsopen allclose all
Dose / conc.:
500 mg/kg bw/day (nominal)
Dose / conc.:
1 000 mg/kg bw/day (nominal)
Dose / conc.:
2 000 mg/kg bw/day (nominal)
No. of animals per sex per dose:
Seven/dose group
Control animals:
yes, concurrent vehicle
Positive control(s):
Cyclophosphamide (50 mg/kg bw)

Examinations

Tissues and cell types examined:
Bone marrow smears prepared and polychromatic erythrocytes per animal was scored. The number of normochromatic erythrocytes were also counted and scored for incidence of micronuclei.
Evaluation criteria:
Micronuclei are cicular, but occassionally may be oval or half-moon shaped and have a sharp contour with even staining.
Statistics:
The ratio of polychromatic to normochromtic erythrocytes was calculated together with appropriate group of mean values and standard deviations.
A positive mutagenic response was demoinstrated when a statistically significant, dose-responsive, toixicologically relevant increase in the number of micronucleated polychromatic erythrocytes was observed for iether the 24 or 48-hour kill times compared to their corresponding control group.

Results and discussion

Test results
Key result
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Remarks:
No premature deaths or clinical signs of toxicity observed in any of the animals dosed.
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
The test item was considered to be non-genotoxic under the conditions of the test.
Executive summary:

An in vivo gentoxicity assay was conducted on the substance according to OECD Guideline 474. The results of the test indicates that the substance is non-genotoxic in vivo under the conditions of the study.