Cerium vanadium tetraoxide

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro DNA damage and/or repair study

Remarks:

Type of genotoxicity: DNA damage and/or repair

Type of information:

experimental study

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. Purity of the test substance not reported. Furthermore, the significant inter-indivuidual variations hamper a clear assessment.

Cross-reference

Reason / purpose for cross-reference:

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 sister chromatid exchanges (SCE).

GLP compliance:

no

Type of assay:

sister chromatid exchange assay in mammalian cells

Test material

Test material information

Constituent 1

Reference substance name:

Vanadium(IV) tetraoxide

IUPAC Name:

Vanadium(IV) tetraoxide

Constituent 2

Reference substance name:

12036-73-6

Cas Number:

12036-73-6

IUPAC Name:

12036-73-6

Constituent 3

Reference substance name:

V2O4

IUPAC Name:

V2O4

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): 72 hours after beginning 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): Differential staining of sister chromatids was then carried out exactly as described by Roldán and Altamirano, 1990.

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

NUMBER OF CELLS EVALUATED: Sister chromatid exchanges (SCE) were scored in 60 second mitotic division cells per treatment.

DETERMINATION OF CYTOTOXICITY
- Method: replicative and mitotic index:
400 metaphases were classified as either first, second or third division cycles, according to the differential stain in order to calculate the replicative index (RI) and 8000 cells were counted to estimate the MI. All the slides were coded for analysis.

OTHER EXAMINATIONS:
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 were established by the qui-square test and for the SCE by the ANOVA-Turkey test.

Results and discussion

Test results

Species / strain:

lymphocytes: from humans

Metabolic activation:

without

Genotoxicity:

ambiguous

Remarks:

Only slight increases in SCE were observed at 4µg/mL with interindividual variations in response to vanadium.

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):
ambiguous without metabolic activation

Under the given experimental conditions the test substance vanadium(IV) tetraoxide is capable of inducing cytotoxicity and cytostatic effects.

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 sister chromatid exchanges (SCE). This substance induced a clear dose-response in MI inhibitions and modifications in the RI. In the SCE, a significant increase appeared in the treated group compared with the controls.