Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: 40 CFR798.5395
GLP compliance:
not specified
Type of assay:
mammalian bone marrow chromosome aberration test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8-10 wks old

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
distilled water
Duration of treatment / exposure:
3 consecutive days (62.5-750 mg/kg/dose)
Post exposure period:
24 hrs
Doses / concentrationsopen allclose all
Dose / conc.:
2 000 mg/kg bw (total dose)
Dose / conc.:
1 000 mg/kg bw (total dose)
Dose / conc.:
500 mg/kg bw (total dose)
No. of animals per sex per dose:
3 per group
Control animals:
not specified
Positive control(s):
cyclophosphamide (20 mg/kg/ dose by i.p..injection) was used as the positive control.

Examinations

Evaluation criteria:
The PCEs/ NCEs ratio was determined by counting 1000 erythrocytes, and used as the indicator of toxicity.
Micronuclei are defined as round bodies in cytoplasm with a diameter of 1/20 to 1/5 of an erythrocyte.
They stain intensively, similar to the staining of the main nuclei in the nucleated cells.

Results and discussion

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

Applicant's summary and conclusion

Conclusions:
The above results indicate that under the experimental conditions, ADN significantly increases the micronucleated cell frequency in the Swiss CD-1 mice polychromatic erythrocyte system in a dose -dependent manner, suggesting its cromosome-damage effect in the in vivo assay.