Ilmenite (FeTiO3), conc.

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well-documented publication, test substance isufficiently described.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Comparison of results from mouse bone marrow chromosome aberration and micronucleus tests

Author:

Shelby, M.D.; Witt, K.L.

Year:

1995

Bibliographic source:

Environ. Mol. Mutagen. 25, 302-313

Reference 2

Reference Type:

publication

Title:

Evaluation of a three-exposure mouse bone marrow micronucleus protocol: results with 49 chemicals

Author:

Shelby, M.D.; et al.

Year:

1993

Bibliographic source:

Environ. Mol. Mutagen. 21, 160-179

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Study only reports on isolated machanistic investigations.
Test for induction of micronuclei in bone marrow cells of mice

GLP compliance:

no

Type of assay:

micronucleus 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): titanium dioxide
No further details are given.

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: National Toxicology Program production facility at Taconic Farms
- Age at study initiation: between 9 and 14 weeks
- Weight at study initiation: between 25 and 33 g
- Assigned to test groups randomly: yes
No further details are given.

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

corn oil

Details on exposure:

A volume of 0.4 ml was injected i.p. per mouse.
Dose determination studies: The selection of the maximum dose to be tested for MN induction was based on either mortality, administration characteristics (ability to be administered as a homogeneous suspension), depression in the percentage of bone marrow PCE (no less than 15% of the erythrocytes), or on the maximum dose of 2000 mg/kg/day.

dose regimen:
first experiment 0, 250, 500, 1000 mg/kg bw
second experiment 0, 500, 1000, 1500 mg/kg bw

Duration of treatment / exposure:

24 hours

Frequency of treatment:

3 times at 24-hour intervals

Post exposure period:

24 hours

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0 mg/kg
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
250 mg/kg
Basis:
nominal conc.

Doses / concentrations 3

Remarks:

Doses / Concentrations:
500 mg/kg
Basis:
nominal conc.

Doses / concentrations 4

Remarks:

Doses / Concentrations:
1000 mg/kg
Basis:
nominal conc.

Doses / concentrations 5

Remarks:

Doses / Concentrations:
1500 mg/kg
Basis:
nominal conc.

No. of animals per sex per dose:

5 or more

Control animals:

yes, concurrent vehicle

Positive control(s):

yes, but not further reported

Examinations

Tissues and cell types examined:

Bone marrow and peripheral blood smears (two slides/tissue/mouse) were prepared

Details of tissue and slide preparation:

24 hours after the final injection, smears of the bone marrow cells from femurs were prepared. Air-dried smears were fixed and staine.
2000 polychromatic erythrocytes (PCE) were scored per animal for frequency of micronucleated cells. In addition, the percentage of PCE among the total erythrocyte population in the bone marrow was scored for each dose group as a measure of toxicity.

Evaluation criteria:

To determine whether a specific treatment resulted in a significant increase in MN-PCE, the number of MN-PCE were pooled within each dose group and analysed by a one-tailed trend test.

Statistics:

Data were analysed using the Micronucleus Assay Data Management and Statistical software package (version 1.4) that employed a one-tailed Cochran-Armitage trend test across exposure groups and pairwise comparison between exposure group and concurrent control. The level of significance was set at an alpha level of 0.05.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

other: not reported

Additional information on results:

The MN data on TiO2 described here were originally published by Shelby et al. (1993).
The initial MN experiment on TiO2 (0, 250, 500, 1000 mg/kg bw) gave a significant trend with the effect at the highest dose (1000 mg/kg bw) significantly elevated; however, the effects observed were small.

In a second trial on TiO2 (0, 500, 1000, 1500 mg/kg bw) , a single dose group (1000 mg/kg bw) was significantly elevated. However this result was only seen in a single dose, was not concentration dependent and only of minor significance. Therefore this effect is judged as irrelevant biological fluctuation.

Furthermore the chromosome aberration test also reported in the same reference, no clastogenic effects could be observed at all doses (0, 625, 1250, 2500 mg/kg bw). Thus it can be concluded that TiO2 has no clastogenic effect in vivo.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Under the reported experimental conditions TiO2 did not induce significant elevated levels of micronuclei in the bone marrow cells of the mouse. Therefore TiO2 is considered to be non-mutagenic in this micronucleus assay.