potassium titanium oxide (K2Ti6O13)

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

Study period:

07 January 1999 to 01 February 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Annex V (Ames test).

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

(Date of inspection: 23 March 1998 Date of Signature: 21 July 1998)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

432-240-0

EC Name:

-

Cas Number:

12056-51-8

Molecular formula:

K2Ti6O13

IUPAC Name:

Potassium hexatitanate

Details on test material:

- Substance type: Pale yellow solid, inorganic.
- Physical state: Solid (powder).
- Lot/batch No.: A-8838.
- Storage condition of test material: Room temperature in the dark.

Method

Target gene:

Histidine operon (his) for Salmonella.
Tryptophan operon (trp) for E.Coli.

Species / strain

Species / strain 1

Species / strain / cell type:

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

Details on mammalian cell type (if applicable):

Not applicable.

Additional strain / cell type characteristics:

other: Including a deletion through the excision repair gene (uvrB-) which renders the capability of DNA exision repair and deep rough mutation (rfa)

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Details on mammalian cell type (if applicable):

Not applicable.

Additional strain / cell type characteristics:

other: Including a deletion through the excision repair gene (uvrA-)

Metabolic activation:

with and without

Metabolic activation system:

Aroclor induced, rat-liver S9.

Test concentrations with justification for top dose:

Preliminary Toxicity Test: 0, 0.15, 0.5, 1.5, 5, 15, 50, 150, 500, 1500 and 5000 µg/plate
Main test, experiments 1&2: 50, 150, 500, 1500 and 5000 µg/plate (with and without metabolic activation)

Vehicle / solvent:

Sterile distilled water

Controls

Controls 1

Untreated negative controls:

other: (concurrent untreated control)

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

Remarks:

Without S9 mix

Controls 2

Untreated negative controls:

other: (concurrent untreated control)

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

Remarks:

Without S9 mix

Controls 3

Untreated negative controls:

other: (concurrent untreated control)

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

Without S9 mix

Controls 4

Untreated negative controls:

other: (concurrent untreated control)

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene

Remarks:

With S9 mix

Controls 5

Untreated negative controls:

other: (concurrent untreated control)

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

Remarks:

With S9 mix

Details on test system and experimental conditions:

Concentration of the test substance resulting in precipitation: 5000 µg/plate

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48 h.

NUMBER OF REPLICATIONS: Triplicate.

DETERMINATION OF CYTOTOXICITY: Plates were assessed for effects on the growth of the bacterial background lawn.

OTHER EXAMINATIONS
- Other:
Solubility: Test material precipitation was examined on the plates.
Sterlility: (Preliminary study only) The aliquot of 0.1 ml of the maximum concentration of the test material (5000 µg/plate) and 2 ml of molten, trace histidine or tryptophan supplemented, top agar was overlaid onto a sterile Vogel-Bonner Minimal agar plates in order to assess the sterility of the test material.

Evaluation criteria:

A test material may be considered positive in the test system if the following criteria are met: the test material should have induced a reproducible, dose-related and statistically significant increase in the relevant count in at least one strain of bacteria.

Statistics:

Dunnett’s method of linear regression.

Results and discussion

Test results

Test results 1

Species / strain:

other: S. typhimurium TA 100, E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

not determined

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

(> 5000 µg/plate)

Vehicle controls validity:

not examined

Untreated negative controls validity:

not applicable

Positive controls validity:

not applicable

Test results 2

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:

cytotoxicity

Remarks:

(> 5000 µg/plate)

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

No significant increases in the frequency of revertant colonies were recorded for any of the strains of bacteria, at any dose level either with or without
metabolic activation.

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: A black particulate precipitate was observed at 5000 pg/plate, this did not prevent the scoring of revertant colonies.

RANGE-FINDING/SCREENING STUDIES: The test material was non-toxic to the strains of bacteria used

COMPARISON WITH HISTORICAL CONTROL DATA: All positive control chemicals gave increases in revertants, either with or without the metabolising system as appropriate, within expected ranges. No statistically significant increase in the numbers of revertant colonies was recorded for any of the bacterial strains with any dose of the substance, either with or without metabolic activation.
Solvent control plates gave counts of revertant colonies within the normal range.

INFORMATION ON CYTOTOXICITY: No toxicity was exhibited to any of the strains of bacteria used.

Remarks on result:

other: other: preliminary test

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Negative with and without metabolic activation.
The test material was considered to be non-mutagenic under the conditions of this test.

Executive summary:

The test was conducted at a GLP facility in accordance with adopted test guidelines. The study outcomes were presented in well-documented report format. Therefore a reliability of 1 is assigned.

No significant increases in the frequency of revertant colonies were recorded for any of the bacterial strains, with any dose of the test material, either with or without metabolic activation. The test material was considered to be non-mutagenic under the conditions of this test.