[No public or meaningful name is available]

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:

January 2022

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2022

Report date:

2022

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:

Anatase, rutile, disodium hexatitanate and sodium tetratitanate

IUPAC Name:

Anatase, rutile, disodium hexatitanate and sodium tetratitanate

Specific details on test material used for the study:

Batch No.: OP.1501019

Method

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Additional strain / cell type characteristics:

other: five histidine defiient mutant strains

Metabolic activation:

with and without

Metabolic activation system:

The S9 fraction was used as a metabolic activation system together with the essential co-factors β-NADP and glucose-6-phosphate to form the “S9 mix”.

Test concentrations with justification for top dose:

The concentrations 156.25 - 312.5 - 625 - 1250 - 2500 - and 5000 µg/plate were selected based on the results obtained during the initial toxicity mutation test.

Vehicle / solvent:

dimethyl sulfoxide

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

dimethyl sulfoxide

True negative controls:

no

Controls 2

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

These substances were used as positive control in the presence of metabolic activation

Controls 3

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

mitomycin C

Remarks:

These substances were used as positive control in the absence of metabolic activation

Rationale for test conditions:

An initial toxicity-mutation test was performed for the selection of test concentrations for the mutation assay. All strains were tested at eight concentrations (1.5 - 5 - 15 - 50 - 150 - 500 - 1500 - 5000 ug/plate) of the test item, in the presence and absence of metabolic activation along with negative control (DMSO).

Evaluation criteria:

A result was considered positive as concentration-related increase over the range tested and/or a reproducible increase at one or more concentrations in the number of revertant colonies per plate in at least one strain with or without any metabolic activation system.

Statistics:

Simple linear regression analysis was performed for tester strains TA1537, TA1535, TA98, TA100, and TA102, separately, to assess the dose-dependent nature of any increase in revertant colonies.

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

True negative controls validity:

not examined

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium 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

True negative controls validity:

not examined

Positive controls validity:

valid

Test results 3

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

True negative controls validity:

not examined

Positive controls validity:

valid

Test results 4

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

True negative controls validity:

not examined

Positive controls validity:

valid

Test results 5

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

True negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

Based on the study results, it is concluded that the test item is "non-mutagenic" to any strain of Salmonella typhimurium TA1537, TA1535, TA98, TA100, and TA102, when tested under the specified conditions.

Applicant's summary and conclusion

Conclusions:

Under test conditions, the test item was not mutagenic nor cytotoxic.