Registration Dossier

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

Administrative data

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1995

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 473 (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
Details on test material:
- Name of test material (as cited in study report): Bismuth Vanadate
- Molecular formula (if other than submission substance): BiVO4
- Molecular weight (if other than submission substance): 323.92
- Physical state: yellow powder
- Analytical purity: >99.5% w/w
- Impurities (identity and concentrations): water and others, <0.5% w/w
- Lot/batch No.: BVB-1018
- Stability under test conditions: stable
- Other: melting point>800°C

Method

Target gene:
not applicable
Species / strain
Species / strain / cell type:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Metabolic activation system:
S9-mix from treated SD rats
Test concentrations with justification for top dose:
0, 313, 625, and 1250 µg/ml without S9-mix and 0, 1250, 2500 and 5000 µg/ml with S9-mix
Vehicle / solvent:
- Solvent used: CMC (carboxymethyl cellulose), 0.5%
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: MMC without S9-mix, MMC and CPA with S9-mix
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium

DURATION
- Exposure duration: 24 or 48 hours without metabolic activation, 6 hours with metabolic activation

SPINDLE INHIBITOR (cytogenetic assays): colcemide

NUMBER OF CELLS EVALUATED: 100-200

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; relative total growth
Evaluation criteria:
not tranlated from japanese
Statistics:
not reported

Results and discussion

Test results
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
In every test under all concentration range, the test substance did not induce any chromosome aberration, i.e. polyploidy and structural (see Table2)
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
see Table 1
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid

Any other information on results incl. tables

Table 1: Cell growth index

 

Without metabolic activation

With metabolic activation

 

Concen-tration (µg/ml)

Cell growth index (%)

Frequency of mitotic cells

Frequency of aberration cells (50 cells)

 

Concentra-tion (µg/ml)

Cell growth index (%)

Frequency of mitotic cells

Frequency of aberration cells (50 cells)

Polyploid

Structural

Polyploid

Structural

 

 

 

24 hours treatment

0

100

++

0

0

 

 

 

+ S9 mix

0

100

++

0

0

39.1*

92.1

++

2

0

625*

91.9

++

2

0

78.1*

90.5

++

0

0

1250*

93.8

++

4

0

156*

75.5

++

0

0

2500*

97.5

++

2

2

313*

67.6

++

0

0

5000*

92.5

++

4

0

625*

51.9

++

0

0

X

X

X

X

X

1250*

41.5

+

2

0

X

X

X

X

X

2500*

39.8

±

X

X

X

X

X

X

X

5000*

46.9

-

X

X

X

X

X

X

X

48 hours treatment

0

100

++

0

0

 

 

-S9 mix

0

100

++

0

0

156*

93.3

++

0

0

625*

85.4

++

0

0

313*

84.2

++

0

0

1250*

81.7

++

0

0

625*

62.3

++

0

0

2500*

82.3

++

4

0

1250*

34.4

+

4

0

5000*

36.6

++

0

2

2500*

23.2

-

X

X

X

X

X

X

X

5000*

25.2

-

X

X

X

X

X

X

X

*Average of 2 plates; ++Many mitotic cells; +Small amount of mitotic cells; ±Very small amount of mitotic cells; -No mitotic cells

Table 2: Results of chromosomal aberration test (without metabolic activation)

 

Treatment

Treatment time (h)

Concentration (µl/ml)

Total observe (100+100)

Total number of polyploids

Judg-ment

Number and percentage (%) of cells showing chromosomal aberrarions

Gap

Chromatid-type

Chromodome-type

Others

Total

Judg-ment

g

ctb

cte

csb

cse

-g

+g

Solvent (0.5% CMC)

24

0

200

1 (0.5)

 

0 (0.0)

0 (0.0)

1 (0.5)

0 (0.0)

0 (0.0)

0 (0.0)

1 (0.5)

1 (0.5)

 

48

0

200

0 (0.0)

 

0 (0.0)

0 (0.0)

1 (0.5)

0 (0.0)

1 (0.5)

0 (0.0)

2 (1.0)

2 (1.0)

 

 

 

Test substance

 

24

313*

200

1 (0.5)

-

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

-

625*

200

2 (1.0)

-

0 (0.0)

0 (0.0)

1 (0.5)

0 (0.0)

0 (0.0)

0 (0.0)

1 (0.5)

1 (0.5)

-

1250*

200

5 (2.5)

-

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

1 (0.5)

0 (0.0)

1 (0.5)

1 (0.5)

-

 

48

313*

200

2 (1.0)

-

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

1 (0.5)

0 (0.0)

1 (0.5)

1 (0.5)

-

625*

200

4 (2.0)

-

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

-

1250*

200

5 (2.5)

-

0 (0.0)

0 (0.0)

0 (0.0)

0 (0.0)

1 (0.5)

0 (0.0)

1 (0.5)

1 (0.5)

-

Positive control (MMC)

24

0.05

200

1 (0.5)

-

2 (1.0)

17 (8.5)

54 (27.0)

0 (0.0)

1 (0.5)

0 (0.0)

69(34.5)

71(35.5)

++

48

0.05

200

3 (1.5)

-

7 (3.5)

16 (8.0)

98 (49.0)

2 (1.0)

7 (3.5)

0 (0.0)

114(57.0)

119(59.5)

+++

Fill in the number of cells observed, polyploids and cells showing total structural chromosomal aberrations in 2 plates, and the percentage (%) of cells showing aberrations in parenthesis with every concentration of treatment. Gap (g) – Fill in the total value of chromatd-type and chromosome-type. Sum total (-g) – Fill in the total number and percentage of cells except those which has only gaps. If there are many aberrations in one cell, calculate that cell as one cell showing aberrations. For example, if there are 2 exchanges in one cell, calculate that cell as one showing aberrations. One cell showing break and one cell showing exchange. ctb: chomatid break; cte: chromatid exchange; cse: chromosome exchange; others: fragmentation etc. (except pulverization)

Applicant's summary and conclusion

Conclusions:
The test substance bismuth vanadate was not cytogenic in the in vitro chromosome aberration test with Chinese hamster lung fibroblasts, both with and without metabolic activation, when tested up to cytotoxic concentrations.