Ilmenite (FeTiO3), conc.

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:

key study

Study period:

1996-10-14 to 1996-10-25

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well-documented guideline study. However, the kind of the TiO2 treatment is eliminated in the study report. There are a few GLP deviations which are considered not to affect the validity of the conclusions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Titanium dioxide

EC Number:

236-675-5

EC Name:

Titanium dioxide

Cas Number:

13463-67-7

IUPAC Name:

dioxotitanium

Constituent 2

Reference substance name:

Rutile (TiO2)

EC Number:

215-282-2

EC Name:

Rutile (TiO2)

Cas Number:

1317-80-2

IUPAC Name:

dioxotitanium

Details on test material:

- Name of test material (as cited in study report): treated titanium dioxide
- Substance type: white powder (sub micron particle size)
- Analytical purity: 98.5%
- Lot/batch No.: HT5G5 F606 404 30
- Storage condition of test material: ambient temperature in the dark
No further details are given.

Method

Target gene:

Detection of reversion to amino acid independence: his- to his+ for S. typhimurium, trp- to trp+ for E.coli strains

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

Species / strain 3

Species / strain / cell type:

E. coli WP2

Metabolic activation:

with and without

Metabolic activation system:

S9-mix

Test concentrations with justification for top dose:

100, 200, 500, 1000, 2500 and 5000 µg/plate

Vehicle / solvent:

dried ethanol (99.7-100% pure)

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

dried ethanol (99.7-100%)

True negative controls:

no

Positive controls:

yes

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

Remarks:

Migrated to IUCLID6: further control substances see attaced table

Details on test system and experimental conditions:

Treated TiO2 dissolved in dried ethanol was initially assayed using the standard plate incorporation protocol with 6 doses in the range of 100 to 5000 µg per plate, both in the presence and absence of S9 prepared from the livers of phenobarbital/ß-naphthoflavone induced male SD rats. The TiO2 was subsequently re-tested in all six strains over the same dose range; the S9-mix phase of this second assay was conducted using a pre-incubation protocol. The incubation period for each experiment was 3 days at 37˚C.
Solvent control (dried ethanol) and positive control substances were tested to validate the bacterial strains and to confirm the activity of S9-mix.

Evaluation criteria:

Induction of reproducible increases in the numbers of revertants.

Statistics:

one-tailed Student's t-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

Untreated negative controls validity:

not examined

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

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Test results 3

Species / strain:

E. coli WP2

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:

In two separate experiments, treated TiO2 did not induce any significant, reproducible increases in the observed numbers of revertant colonies in any of the tester strains used, either in the presence or absence of 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 metabolic activation
negative without metabolic activation

Under the conditions of this assay, treated TiO2 gave a negative, i.e. non-mutagenic response in S. typhimurium strains TA1535, TA1537, TA98 and TA100 and E. coli strains WP2P and WP2PuvrA in both the presence and absence of S9.