Registration Dossier

Administrative data

Endpoint:
in vivo mammalian germ cell study: cytogenicity / chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for data waiving:
other:
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1978
Report Date:
1977

Materials and methods

Principles of method if other than guideline:
Animals were exposed to test material by inhalation and sacrificed after treatment. Chromosome preparations were made from the bone marrow cells and stained. Cells were analysed for chromosome aberrations.
GLP compliance:
not specified
Type of assay:
chromosome aberration assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Zinc oxide

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Not reported

Administration / exposure

Route of administration:
inhalation
Vehicle:
Not applicable
Details on exposure:
The exposure chambers were equipped with dosing devices, to ensure a constant concentration throughout the exposure period, with a fluctuation not exceeding +/- 10% of the set values of 0.1 and 0.5 mg/m3.
Duration of treatment / exposure:
5 months
Frequency of treatment:
Animals were exposed to the test material aerosol continuously
Post exposure period:
Not reported
Doses / concentrations
Remarks:
Doses / Concentrations:
0.5 and 0.1 mg/m3
Basis:
nominal conc.
No. of animals per sex per dose:
Not reported
Control animals:
yes
Positive control(s):
Not reported

Examinations

Tissues and cell types examined:
Bone marrow cells examined for all types of chromosome and chromatid-type aberrations and hyperdiploid cells.
Details of tissue and slide preparation:
Specimens were prepared according to Tjio and Whang (1962) method.
Evaluation criteria:
Not reported
Statistics:
Frequencies of chromosome damages, the Student criterion and the confidence intervals were calculated using the Fisher transformation. The level of significance was 0.05.

Results and discussion

Test results
Sex:
female
Genotoxicity:
positive
Toxicity:
not specified
Vehicle controls validity:
not specified
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Additional information on results:
RESULTS OF DEFINITIVE STUDY

- Statistical evaluation: Both the total number of cells with chromosomal damage and frequency of hyperdiploid cells were increased significantly (p<0.05) at 0.1 and 0.5 mg/m3.

Any other information on results incl. tables

Frequency of cells with chromosome damages (%) in the bone marrow:

 Type of chromosome damages 

 Control   

    ZnO (mg/m3)

 0.1

 0.5

Structural aberrations  0  1.0  0.5
Hyperdiploid cells  1.0  3.5*  6.0*
Total cells damaged  1.0  4.5*  6.5*
Metaphases studied  200  200  200

*significant at p<0.05

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: weakly positive
The test material caused a statistically significant increase in the frequency of damaged cells, primarily hyperdiploid under the conditions of this test.
Executive summary:

A study was conducted to determine the potential genotoxicity of the test material using chromosomal aberration assay. 

Non-inbred female white rats were exposed to the test material aerosols at a concentration of 0.5 and 0.1 mg/m3 continuously for 5 months. The samples for chromosomal analysis were prepared according to Tjio and Whang (1962) method.

Statistically significant increase in the frequency of damaged cells, primarily hyperdiploid cells were observed at both tested concentration.

The test material caused a statistically significant increase in the frequency damaged cells, primarily hyperdiploid under the conditions of this test.