Disodium hexatitanate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 September 2011 - 17 October 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

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:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Disodium hexatitanate

EC Number:

815-182-4

Cas Number:

12058-75-2

Molecular formula:

Na2Ti6O13

IUPAC Name:

Disodium hexatitanate

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

- Analytical purity: 100%
- Purity test date: 19 August 2011
- Lot/batch No.: IC96
- Expiration date of the lot/batch: 24 March 2014
- Storage: room temperature

Method

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Remarks:

E. Coli WP2 uvrA (pKM101)

Details on mammalian cell type (if applicable):

Base change mutagens: S. typhimurium TA 1535, TA 100 and E. coli WP2
Frameshift mutagens: S. typhimurium TA 1537, TA 98

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Test concentrations with justification for top dose:

The highest concentration of test substance tested in this study was 50 mg/ml in the chosen vehicle, which provided a final concentration of 5000 µg/plate. This is a standard limit concentration recommended in the regulatory guidelines that this assay follows.
Test 1: 5, 15, 50, 150, 500, 1500, 5000 µg
Test 2: 15, 50, 150, 500, 1500, 5000 µg

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO

Controls

Untreated negative controls:

yes

Remarks:

Historical data

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

9-aminoacridine

2-nitrofluorene

sodium azide

benzo(a)pyrene

other: 2-Aminoanthracene

Details on test system and experimental conditions:

Two independent mutation tests were performed in the presence and absence of liver preparations (S9 mix) from rats treated with phenobarbital and 5,6-benzoflavone. The first test was a standard incorporation assay; thr second included a pre-incubation stage.

Evaluation criteria:

For a test to be considered valid, the mean of the vehicle control colony numbers for each strain should lie within or close to the 99% confidence limits of the current historical control range of the laboratory unless otherwise justified by the study director. The historical range is mainteined as a rolling record over a maximum of five years. Also, a positive control compounds must include an increase in mean revertant colony numbers of at least twice (three times in case of TA 1535 and TA 1537) the concurrent vehicle controls. Mean viable cell counts in the 10-hour bacterial cultures must be at least 10^9/mL.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 5

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

FIrst test:
No evidence of toxicity was obtained following exposure to test substance. A maximum exposure concentration of 5000 µg/plate was, therefore, selected for use in second test.
No substantial increases in revertant colony numbers over the control counts were obtained with any of the tester strains following exposure to test substance at any concentration up to and including 5000 µg/plate in either the presence or absence of S9 mix.
Second test:
No evidence of toxicity was obtained following exposure to test substance.
No substantial increases in revertant colony numbers over the control counts were obtained with any of the tester strains following exposure to test substance at any concentration up to and including 5000 µg/plate in either the presence or absence of S9 mix.

Applicant's summary and conclusion

Conclusions:

It is concluded that test substance showed no evidence of mutagenic activity in this bacterial system under the test conditions employed.