Niobium sulfur tin zinc oxide

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with acceptable restrictions. Lack of data on analytical purity of the test substance.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

Lack of data on analytical purity of the test substance.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)

Deviations:

yes

Remarks:

Lack of data on analytical purity of the test substance.

GLP compliance:

yes (incl. QA statement)

Remarks:

Bayrisches Landesamt für Gesundheit und Lebensmittelsicherheit, Landesinstitut für Arbeitsschutz und Produktsicherheit, München

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

niobium oxygen sulfur zinc λ²-stannane

EC Number:

800-035-9

Cas Number:

1374645-21-2

Molecular formula:

Sn1.8Zn0.2Nb2O6.8S0.2 (Sn(2-x)Zn(x)Nb2O(7-y)S(y) with x/2 ≤ y, 0.02 ≤ x ≤ 0.22, 0.01 ≤ y ≤ 0.22)

IUPAC Name:

niobium oxygen sulfur zinc λ²-stannane

Details on test material:

- Name of test material (as cited in study report): Niobium Sulfur Tin Zinc Oxide Lot No. Ex 1455
- Physical state: solid
- Appearance: yellow powder
- Analytical purity: no data
- Lot No.: L1903
- Storage condition of test material: at room temperature

Method

Target gene:

his operon and trp operon

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of male Wistar and Sprague Dawley rats treated with a mixture of phenobarbital and β-naphthoflavone

Test concentrations with justification for top dose:

First experiment (plate incorporation test): 31.6, 100, 316, 1000, 2500 and 5000 µg/plate
Second experiment (pre-incubation test): 31.6, 100, 316, 1000, 2500 and 5000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: distilled water

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: -S9: sodium azide (TA 100, TA 1535: 10 µg/plate); 4-nitro-o-phenylene-diamine (4-NOPD, TA98: 10 µg/plate, TA 1537: 40 µg/plate); methylmethanesulfonate (MMS, E. coli WP2 uvrA: 1 µL/plate); +S9: 2-aminoanthracene (2-AA, 2.5 or 10 µg/plate for all strains)

Remarks:

The positive control substances were dissolved in distilled water.

Details on test system and experimental conditions:

METHOD OF APPLICATION: experiment 1: in agar (plate incorporation); experiment 2: preincubation

DURATION
- Preincubation period: 1 h
- Exposure duration: 48 h (both experiments)

NUMBER OF REPLICATIONS: triplicates each in two independent experiments

DETERMINATION OF CYTOTOXICITY
- Method: clearing of the bacterial background lawn or reduction in the number of revertants down to a mutation factor of approximately ≤ 0.5 in relation to the solvent control

Evaluation criteria:

The test substance may be considered positive in this test system if the following criteria are met:
For the test substance to be considered mutagenic, the mean revertant number should increase at least two-fold in the tester strains TA 98, TA 100 and E. coli uvrA or at least three-fold in the tester strains TA 1535 and TA 1537 in comparison to the vehicle control. In addition, a clear and dose-related increase in the number of revertants should be observed.

Statistics:

Mean values and standard deviations were calculated.
To calculate the mutation factor, the following formula was used:
Mutation factor = mean revertants (test substance) / mean revertants (vehicle control)

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

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

Test results 2

Species / strain:

E. coli WP2 uvr A

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:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: At a concentration of 2500 µg/plate and above, the test substance precipitated in the cell culture medium.

RANGE-FINDING/SCREENING STUDIES: In a pre-experiment, concentrations of the test substance in the range of 3.16 to 5000 µg/plate were tested on S. typhimurium strains TA 98 and TA 100 with and without metabolic activation. There were no genotoxic or cytotoxic effects observed up to the highest concentration.

COMPARISON WITH HISTORICAL CONTROL DATA: The vehicle and positive control data with and without metabolic activation are within the ranges of the historical control data estimated between 2008 and 2010.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1: Test results of the pre-experiment

Bacterial Reverse Mutation Assay mutation factor
PRE-EXPERIMENT
S9-Mix	Without
Test item (µg/plate)	TA 98	TA100
Distilled water	1.0	1.0
3.16	1.3	1.1
10.0	0.9	1.1
31.6	1.1	1.1
100	0.9	1.1
316	1.1	1.2
1000	1.2	1.1
2500	0.9	1.0
5000	0.9	1.1
Sodium azide	---	8.1
4-NOPD	20.6	---
S9-Mix	With
Test item (µg/plate)	TA98	TA 100
Distilled water	1.0	1.0
3.16	1.3	1.0
10.0	1.1	0.9
31.6	1.0	1.0
100	0.9	0.9
316	1.2	0.9
1000	1.1	1.1
2500	1.2	1.0
5000	1.1	1.1
2-AA	77.6	16.4
4-NOPD: 4-nitro-o-phenylene-diamine 2-AA: 2-aminoanthracene

Table 2: Test results of experiment 1 - plate incorporation method

Bacterial Reverse Mutation Assay, mean revertant colonies/plate ± SD (mutation factor)
EXPERIMENT 1 (plate incorporation method)
S9-Mix	Without
Test item (µg/plate)	TA 98	TA100	TA 1535	TA1537	E. coli uvrA
Distilled water	19 ± 2.5 (1.0)	105 ± 11.5 (1.0)	8 ± 0.6 (1.0)	9 ± 1.2 (1.0)	59 ± 6.1 (1.0)
31.6	20 ± 5.5 (1.1)	115 ± 2.0 (1.1)	11 ± 0.6 (1.4)	7 ± 1.5 (0.8)	48 ± 4.7 (0.8)
100	17 ± 1.7 (0.9)	113 ± 2.5 (1.1)	8 ± 2.9 (1.0)	9 ± 2.5 (0.9)	53 ± 1.5 (0.9)
316	20 ± 6.0 (1.1)	124 ± 3.5 (1.2)	10 ± 3.1 (1.2)	8 ± 1.2 (0.9)	52 ± 5.3 (0.9)
1000	22 ± 4.7 (1.2)	112 ± 11.6 (1.1)	14 ± 1.2 (1.6)	8 ± 3.8 (0.8)	58 ± 7.6 (1.0)
2500	17 ± 4.0 P (0.9)	108 ± 4.7 P (1.0)	13 ± 2.1 P (1.5)	11 ± 4.6 P (1.2)	48 ± 4.4 P (0.8)
5000	17 P ± 6.0 (0.9)	118 ± 6.1 P (1.1)	11 ± 2.1 P (1.3)	6 ± 1.2 P (0.6)	61 ± 9.2 P (1.0)
Sodium azide	---	851 ± 34.4 (8.1)	950 ± 90.7 (114.0)	---	---
4-NOPD	385 ± 50.6 (20.6)	---	---	99 ± 22.2 (10.6)	---
MMS	---	---	---	---	673 ± 57.7 (11.4)
S9-Mix	With
Test item (µg/plate)	TA98	TA 100	TA 1535	TA 1537	E. coli uvrA
Distilled water	24 ± 4.0 (1.0)	124 ± 12.0 (1.0)	10 ± 3.2 (1.0)	7 ± 2.6 (1.0)	58 ± 5.0 (1.0)
31.6	24 ± 7.5 (1.0)	120 ± 3.8 (1.0)	12 ± 2.3 (1.3)	11 ± 2.1 (1.6)	49 ± 6.2 (0.8)
100	21 ± 5.1 (0.9)	109 ± 6.4 (0.9)	8 ± 2.0 (0.8)	9 ± 3.2 (1.2)	62 ± 13.3 (1.1)
316	28 ± 6.7 (1.2)	117 ± 10.7 (0.9)	10 ± 1.5 (1.0)	11 ± 2.9 (1.6)	57 ± 1.7 (1.0)
1000	27 ± 2.0 (1.1)	131 ± 2.5 (1.1)	9 ± 3.2 (1.0)	10 ± 2.5 (1.4)	57 ± 8.5 (1.0)
2500	28 ± 13.1 P (1.2)	123 ± 11.0 P (1.0)	11 ± 5.1 P (1.2)	10 ± 4.2 P (1.4)	62 ± 6.4 P (1.1)
5000	27 P ± 0.9 (1.1)	130 ± 7.2 P (1.1)	10 ± 2.1 P (1.1)	9 ± 3.1 P (1.2)	61 ± 4.0 P (1.0)
2-AA	1888 ± 152.8 (77.6)	2030 ± 208.6 (16.4)	124 ± 22.6 (12.8)	242 ± 65.1 (34.6)	290 ± 5.5 (5.0)
SD: Standard deviation P: Precipitation 4-NOPD: 4-nitro-o-phenylene-diamine MMS: Methylmethanesulfonate 2-AA: 2-aminoanthracene

Table 3: Test results of experiment 2 - pre-incubation method

Bacterial Reverse Mutation Assay, mean revertant colonies/plate ± SD (mutation factor)
EXPERIMENT 2 (pre-incubation method)
S9-Mix	Without
Test item (µg/plate)	TA 98	TA100	TA 1535	TA1537	E. coli uvrA
Distilled water	22 ± 5.7 (1.0)	113 ± 17.4 (1.0)	10 ± 1.5 (1.0)	5 ± 1.2 (1.0)	62 ± 13.7 (1.0)
31.6	25 ± 2.5 (1.1)	129 ± 16.8 (1.1)	8 ± 3.0 (0.8)	8 ± 2.9 (1.6)	41 ± 3.5 (0.7)
100	20 ± 6.2 (0.9)	133 ± 5.8 (1.2)	10 ± 3.6 (1.0)	5 ± 2.0 (0.9)	50 ± 3.6 (0.8)
316	23 ± 4.9 (1.0)	128 ± 13.0 (1.1)	6 ± 0.6 (0.7)	9 ± 3.6 (1.7)	55 ± 6.9 (0.9)
1000	24 ± 1.7 (1.1)	111 ± 14.4 (1.0)	10 ± 5.5 (1.0)	7 ± 4.9 (1.4)	48 ± 8.5 (0.8)
2500	23 ± 4.0 P (1.0)	118 ± 4.4 P (1.0)	8 ± 0.0 P (0.8)	7 ± 3.8 P (1.4)	58 ± 9.5 P (0.9)
5000	17 ± 2.5 P (0.7)	129 ± 11.6 P (1.1)	10 ± 5.5 P (1.0)	5 ± 0.0 P (0.9)	53 ± 15.2 P (0.8)
Sodium azide	---	839 ± 118.9 (7.4)	823 ± 76.8 (85.2)	---	---
4-NOPD	710 ± 154.7 (31.8)	---	---	100 ± 15.3 (18.8)	---
MMS	---	---	---	---	679 ± 24.5 (10.9)
S9-Mix	With
Test item (µg/plate)	TA98	TA 100	TA 1535	TA 1537	E. coli uvrA
Distilled water	26 ± 2.3 (1.0)	140 ± 23.2 (1.0)	7 ± 2.0 (1.0)	5 ± 1.2 (1.0)	47 ± 4.5 (1.0)
31.6	29 ± 7.9 (1.1)	130 ± 8.4 (0.9)	6 ± 1.5 (0.9)	5 ± 0.6 (0.9)	57 ± 5.5 (1.2)
100	28 ± 4.0 (1.1)	131 ± 7.8 (0.9)	9 ± 4.6 (1.3)	7 ± 4.0 (1.3)	48 ± 7.4 (1.0)
316	29 ± 6.1 (1.1)	141 ± 0.6 (1.0)	8 ± 6.4 (1.2)	4 ± 1.2 (0.8)	66 ± 8.5 (1.4)
1000	34 ± 7.1 (1.3)	135 ± 14.0 (1.0)	6 ± 4.0 (0.9)	5 ± 0.0 (0.9)	61 ± 9.5 (1.3)
2500	34 ± 9.0 P (1.3)	142 ± 18.6 P (1.0)	7 ± 1.5 P (1.0)	6 ± 1.5 P (1.2)	54 ± 9.7 P (1.1)
5000	35 ± 7.1 P (1.4)	150 ± 6.7 P (1.1)	7 ± 2.1 P (1.0)	6 ± 1.0 P (1.1)	50 ± 8.5 P (1.1)
2-AA	1060 ± 171.8 (41.3)	731 ± 18.6 (5.2)	27 ± 2.5 (3.8)	100 ± 7.6 (18.7)	154 ± 25.4 (3.2)
SD: Standard deviation P: Precipitation 4-NOPD: 4-nitro-o-phenylene-diamine MMS: Methylmethanesulfonate 2-AA: 2-aminoanthracene

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative