Registration Dossier

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

Administrative data

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2006-05-02 - 2006-06-16
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well-documented guideline study. No data on particle size distribution are given.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EPA OPPTS 870.5375 - In vitro Mammalian Chromosome Aberration Test
Qualifier:
according to
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Qualifier:
according to
Guideline:
EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
GLP compliance:
not specified
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Target gene:
no data
Species / strain
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Details on mammalian cell type (if applicable):
The CHO-K1 cell line was originally derived as a subclone from a parental CHO cell line. The cells require proline in the medium for growth, and have a modal chromosome number of 20. The population doubling time is 10-14 hours. The cell line was obtained from the American Type Culture Collection (ATCC number CCL 61), Manassas, Virginia. The karyotype and the absence of mycoplasm infection are routinely checked by Haskell Laboratory.
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9 activation system
Test concentrations with justification for top dose:
125, 250, 750, 1250, and 2500 μg/ml
Vehicle / solvent:
The test substance was prepared in sterile water as this vehicle was determined to be the solvent of choice based on the solubility of the test substance and compatibility with the target cells.
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
mitomycin C
Remarks:
The positive controls were dissolved in sterile water.

Migrated to IUCLID6: and cyclophosphamide
Details on test system and experimental conditions:
The test substance, as well as positive and negative (vehicle) controls, was administered in the presence and absence of an exogenous S9 metabolic activation system to cell cultures by addition to the culture medium. In the non-activated test system, the treatment times were approximately 4 and 20 hours, and in the S9-activated test system, approximately 4 hours. The dividing cells were arrested in metaphase approximately 18 hours after initiation of the treatment and harvested at approximately 20 hours.
To prepare slides, the cells were collected by centrifugation and
resuspended in fresh fixative. At least two slides per culture were prepared by applying an aliquot of the fixed cells onto clean microscope slides and air-drying them. The slides were stained by Giemsa and permanently mounted.
Evaluation criteria:
The clastogenic potential of the test substance was assessed based on its ability to induce structural chromosome aberrations. The experimental unit is the cell; therefore the percentage of cells with structural aberrations was used for the assessment.
Statistics:
Statistical analysis was used as a guide to determine whether or not the test substance induced a positive response.

Results and discussion

Test results
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
Under the conditions of this study, titanium dioxide (sample: H-27416) was not found to induce structural or numerical chromosome aberrations in the in vitro mammalian chromosome aberration test in Chinese hamster ovary cells in either the non-activated or S9-activated test conditions.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

The test substance was concluded as negative in this in vitro test.