Niobium carbide

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

2000-10-11 to 2001-02-27

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study. Niobium pentoxide is used as read across partner.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

niobium pentoxide

IUPAC Name:

niobium pentoxide

Constituent 2

Reference substance name:

Diniobium pentaoxide

EC Number:

215-213-6

EC Name:

Diniobium pentaoxide

Cas Number:

1313-96-8

Molecular formula:

Nb2O5

IUPAC Name:

diniobium pentaoxide

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Nb2O5 Niobium Pentoxide Grade LN
- Physical state: solid
- Analytical purity: 99.99%
- Lot/batch No.: 20000103
- Storage condition of test material: Room temperature, in the dark under dry conditions

Method

Target gene:

S. typhimurium: histidine
E. coli: tryptophan

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 pKM 101

Metabolic activation:

with and without

Metabolic activation system:

microsomal liver enzymes (S9)

Test concentrations with justification for top dose:

Test 1 (dose range finding) 5, 15, 50, 150, 500, 1500 and 5000 µg/plate
Test 2: 50, 150, 500, 1500 and 5000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: water containing 0.15% agar
- Justification for choice of solvent/vehicle: the test substance was found to be insufficiently soluble in all compatible solvents.

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

Purified water + 0.15% agar

True negative controls:

no

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

Remarks:

5 μg/plate

Migrated to IUCLID6: strains TA98, TA1537 and TA100 with S9

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

Purified water + 0.15% agar

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

1 μg/plate

Migrated to IUCLID6: strain TA98 without S9

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

Purified water + 0.15% agar

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

0.5 μg/plate

Migrated to IUCLID6: strain TA100 and TA1535 without S9

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

Purified water + 0.15% agar

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene strains TA1535 and E.coli with S9

Remarks:

10 μg/plate

Controls 5

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

Purified water + 0.15% agar

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

30 μg/plate

Migrated to IUCLID6: strain TA1537 without S9

Controls 6

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

Purified water + 0.15% agar

Positive controls:

yes

Positive control substance:

other: AF-2 for E.coli without S9

Remarks:

0.05 μg/plate

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation); preincubation;
DURATION
- Preincubation period: 30 minutes (only for 2nd test, 1st test without preincubation)
- Exposure duration: 72 hours
- Fixation time (start of exposure up to fixation or harvest of cells): 72 hours

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth

Evaluation criteria:

VALIDITY CRITERIA
For a test to be considered valid the mean of the solvent/vehicle control revertant colony numbers for each strain should lie within the 99% confidence limits of the current historical control range of the laboratory. Also, the positive control compunds must cause at least a doubling of mean revertantcolony numbers over the negative control

EVALUATION CRITERIA
The mean number of revertant colonies for each treatment group was compared with those obtained for the solvent/vehicle control groups. The mutagenic activity of a test substance was assessed by applying the following criteria:
a) If treatment with a test substance produces an increase in revertant colony numbers of at leasttwice the concurrent solvent/vehicle controls, with some evidence of a positive dose relationship, in two separate experiments, with any bacterial strain either in the presence or absence of S9 mix, the test substance will be considered to show evidence of mutagenic activity in this test system. No statistical analysis will be performed.
b) If treatment with a test substance does not produce reproducible increases of at least 1.5 times the concurrent solvent/vehicle controls in either mutation test, the test substance will be considered to show no evidence of mutagenic activity in this test system. No statistical analysis will be performed.
c) If the results obtained fail to satisfy the criteria for a clear "positive" or "negative" response given in paragraphs a) and b ), even after the additional testing outlined in the mutation test procedure, the test data may be subjected to analysis to determine the statistical significance of any increases in revertant colony numbers. Biological significance should always be considered along with statistical significance. It should be noted that it is acceptable to conclude an equivocal response if no clear results can be obtained.

Statistics:

The statistical procedures will usually be analysis of variance followed by Dunnett's test

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

Positive controls validity:

valid

Test results 2

Species / strain:

E. coli WP2 uvr A pKM 101

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

RANGE-FINDING/SCREENING STUDIES:
1st Test:
The test substance was added to cultures of the five tester strains at seven concentrations separated by ca half-log10 intervals. The highest concentration of Nb20 5 Niobium Pentoxide Grade LN tested was 50 mg/ml in the chosen solvent, which provided a final concentration of 5000 μg/plate.
COMPARISON WITH HISTORICAL CONTROL DATA:
The mean revertant colony counts for the solvent controls were within the 99% confidence limits of the current historical control range of the laboratory (except strain TA98, test 1, where counts were slightly higher; this was not considered to affect the integrity of the study). Appropriate positive
control chemicals (with S9 mix where required) induced substantial increases in revertant colony numbers with all strains, confirming sensitivity of the cultures and activity of the S9 mix.

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):
negative (with and without metabolic activation)

It is concluded that under the test conditions employed, Nb2O5 Niobium Pentoxide Grade LN showed no evidence of mutagenic activity in this bacterial system.

Executive summary:

In a reverse gene mutation assay in bacteria (OECD 471), S. typhimurium strains TA1535, TA1537, TA98, TA100 and E. coli strain WP2uvrA were exposed to Niobium Pentoxide Grade LN (99.99 purity) at concentrations of 5, 15, 50, 150, 500, 1500 and 5000 µg/plate in the presence and absence of mammalian metabolic activation.

Niobium Pentoxide Grade LN was tested up to the limit concentration of 5000 µg/plate. The positive controls induced the appropriate responses in the corresponding strains. The vehicle control data was within the 99% confidence limits of the current historical negative control range, except strain TA98, test 1, where counts were slightly higher, but this was not considered to affect the integrity of the study. There was no evidence of induced mutant colonies over background.

This study is classified as acceptable and satisfies the requirement for Test Guideline OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation assay). Niobium pentoxide is used as read across partner to niobium carbide.