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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
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:
no data available
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Reasonably well described study. However, due to the missing positive control, the positive findings can not be properly evaluated- historical data are not reported. Furthermore the following experimental deficiencies restrict the use for hazard assessment: exposure towards test substance commenced 24h after mitogenic stimulation (guideline foresees 48h). Cell cycle length not determined. Purity of the test substance not reported.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Genotoxic effects of vanadium(IV) in human peripheral blood cells.
Author:
Rodriguez-Mercado, J.J.; et al.
Year:
2003
Bibliographic source:
Toxicology letters, 144, 359-69.

Materials and methods

Test guideline
Guideline:
other: no information available if test was conducted according to guideline
Principles of method if other than guideline:
In this study, the genotoxicity of vanadium(IV) tetraoxide was evaluated in human cultured lymphocytes and leukocytes using the mitotic index (MI), the replicative index (RI) and chromosome aberration test (CA).
GLP compliance:
no
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Test material form:
other: solid
Details on test material:
- Name of test material (as cited in study report): Vanadium(IV) tetraoxide
- Physical state: solid

Method

Target gene:
not applicable
Species / strain
Species / strain / cell type:
lymphocytes: from human donors
Details on mammalian cell type (if applicable):
The study was conducted with peripheral blood lymphocytes obtained by venipuncture from 3 healthy non-smoking males between 23 and 29 years of age.
- Type and identity of media: Some 0.5 mL of heparinised blood was cultured in 4.5 mL of RPMI-1640 culture medium with 5 µg/mL of phytohaemaglutinin. Cells were cultured for 24 hours.
No further details are reported.
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
without
Test concentrations with justification for top dose:
2, 4, 8 or 16 µg/mL
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: distilled water
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
distilled water
True negative controls:
no
Positive controls:
no
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium

DURATION
- Exposure duration: 48 hours
- Fixation time (start of exposure up to fixation or harvest of cells): After 48 hours the cultures were harvested, fixed and prepared on flame-dried slides.

SPINDLE INHIBITOR (cytogenetic assays): 4 µg/mL of colchicine were added to each culture 2 hours before the harvest.
STAIN (for cytogenetic assays): Slides were stained with Giemsa.

NUMBER OF REPLICATIONS: All cultures were set up in duplicate.

NUMBER OF CELLS EVALUATED: 200 well-spread metaphases for each treatment were analysed.

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index:
8000 cells were counted to estimate the mitotic index (MI).

OTHER EXAMINATIONS:
The type of CA scored included chromatid and chromosome-types as well as gaps.
No further details are given.
Evaluation criteria:
No data given.
Statistics:
The significant statistical differences for the MI were determined by the z-test; the statistical differences for the RI and CA were established by the qui-square test.

Results and discussion

Test results
Species / strain:
lymphocytes: from humans
Metabolic activation:
without
Genotoxicity:
positive
Remarks:
The frequency in all types of aberrations (i.e. acentric fragments and breaks, as well as exchanges) was higher in the treated group than in the controls. The percentage of aberrant cells (without gaps) was significantly different.
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
A significant decrease was noted in the frequency of mitoses detected. Also, a gradual decline appeared in the inhibition of MI percentage.
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
not examined
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
No data are reported.

RANGE-FINDING/SCREENING STUDIES: No details are reported, but concentrations tested were selected on the basis of preliminary experiments.

COMPARISON WITH HISTORICAL CONTROL DATA: no

ADDITIONAL INFORMATION ON CYTOTOXICITY: no further details
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):
positive without metabolic activation

Under the given experimental conditions the test substance vanadium(IV) tetraoxide is capable of inducing chromosomal damage.
Executive summary:

In this study, the genotoxicity of vanadium(IV) tetraoxide was evaluated in human cultured lymphocytes and leukocytes using the mitotic index (MI), the replicative index (RI) and chromosome aberration (CA). This substance induced a clear dose-response in MI inhibitions and modifications in the RI. In the CA, including breaks and exchanges, a significant increase appeared in the treated group compared with the controls.