Registration Dossier

Toxicological information

Genetic toxicity: in vivo

Currently viewing:

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:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Similar to the guideline but the toxicity is not evaluated. The objective was to define the best sampling time for the guideline.

Data source

Reference
Reference Type:
publication
Title:
An optimal, generalized sampling time of 30 ± 6 h after double dosing in the mouse peripheral blood micronucleus test
Author:
Higashikuni N, Sutou S
Year:
1995
Bibliographic source:
Mutagenesis 10(4): 313-319

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Deviations:
yes
Remarks:
toxicity is not assessed
Guideline:
EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
Principles of method if other than guideline:
Additional sampling time were included in the study
GLP compliance:
no
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
supplier: Nacalai Tesque Inc (Japan)

Test animals

Species:
mouse
Strain:
other: MS/Ae
Sex:
male/female

Administration / exposure

Route of administration:
intraperitoneal
Duration of treatment / exposure:
Injected twice, at 24 h interval.
Frequency of treatment:
see above
Post exposure period:
24 to 60 h after the 2nd treatment
Doses / concentrations
Remarks:
Doses / Concentrations:
80 and 160 mg/kg
Basis:
nominal conc.
No. of animals per sex per dose:
5
Control animals:
other: Same animals, sampling time before treatment

Examinations

Tissues and cell types examined:
reticulocytes

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
positive
Toxicity:
not examined
Vehicle controls validity:
not specified
Negative controls validity:
valid
Positive controls validity:
not examined

Any other information on results incl. tables

Dose
(mg/kg)

Sampling time (h)

Number of animals

Mean MN/1000 RET

SD

80

0

5

3.20

1.64

24

8.60

1.67

30

9.00

5.10

36

7.40

2.07

42

5.60

2.07

48

2.80

1.92

54

2.20

2.49

60

2.20

1.92

160

0

5

3.00

1.00

24

4

8.75

2.87

30

15.50

3.32

36

13.25

2.50

42

9.75

2.06

48

8.75

2.36

54

6.75

1.26

60

2.75

1.50

MN = micronucleated cell

RET = reticulocytes

SD = standard deviation

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): positive
DES induced micronucleus in the reticulocytes of mouse. Peak responses are observed around 30 h after the second treatment.
Executive summary:

A micronucleus test was performed in mice treated by ip with 80 or 160 mg/kg (2 injections). Sampling time was between 24 and 60 h after the second injection.

In the conditions of this test, DES induced micronucleus, the peak response was between 34 and 36 h.