Bismuth bromide iodide oxide

Genetic toxicity: in vitro

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

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

Test material information

Constituent 1

Reference substance name:

Bismuth vanadium tetraoxide

EC Number:

237-898-0

EC Name:

Bismuth vanadium tetraoxide

Cas Number:

14059-33-7

Molecular formula:

BiO4V

IUPAC Name:

bismuth; oxygen(2-); vanadium

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.