Reaction mass of disodium hexatitanium tridecaoxide and disodium trititanium heptaoxide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Sodium titanates are effectively the sodium salts of the unstable titanic acid (titanium hydroxide). Titanium hydroxide is hard to isolate without rapid hydrolysis to titanium dioxide and sodium chloride. It is therefore proposed to base environmental and health assessment on these two hydrolysis products. There has been extensive research on similar substances in the ‘titanate’ grouping and these all exhibit similar behaviour in that under acid biological conditions (eg if ingested) or if dispersed in water, there is dissociation of the ions and subsequent hydrolysis / oxidation. Read-across justification for the use of TiO2 data is available in section 13.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Fischer 344 male rats were exposed either with whole-body or nose-only inhalation for 6 hrs. Control animals were exposed to fresh air only. After the exposue period of 6 hrs animals were immediately sacrificed by overdose of phenobarbital. The body weights were recorded, the lungs were collected and the wet lung weights measured. The right lung was used for determining the amounts of TiO2, while the left lung was used for histopathological examination

GLP compliance:

not specified

Remarks:

All procedures and animal handling were done according to the guidelines described in the Japanese Guide for the Care and Use of Laboratory Animals as approved by the Animal Care and Use Committee University of Occupational and Environmental Health Japan.

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Titanium dioxide

EC Number:

236-675-5

EC Name:

Titanium dioxide

Cas Number:

51745-87-0

Molecular formula:

O2Ti

IUPAC Name:

Titanium dioxide

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Nano-scale TiO2 (MT-150AW, TAYCA, Japan)

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

Fifteen Fischer 344 male rats (11 weeks old) were purchased from Charles River Laboratories International, Inc. (Japan). The animals were kept in the Laboratory Animal Research Center of the University of Occupational and Environmental Health for 1 week with access to free-feeding of commercial diet and water. All procedures and animal handling were done according to the guidelines described in the Japanese Guide for the Care and Use of Laboratory Animals as approved by the Animal Care and Use Committee, University of Occupational and Environmental Health, Japan.

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

other: whole body and nose only

Vehicle:

air

Details on inhalation exposure:

Rats were divided into three groups of five rats each for whole-body inhalation and for nose-only inhalation of TiO2 for 6 h, and for controls exposed to fresh air only.
Titanium dioxide powder was suspended in ultra-pure water for nanoparticle generation. The TiO2 concentration in the chambers was measured every hour by weighing the filtered particles.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

The TiO2 in each right lung were digested with lung tissues with HNO3 H2SO4, (NH4)2SO4 and H2O2 by microwave digestion under a high-temperature and highpressure condition for 30 min and the amounts of Ti ion in the digested solution were determined by ICP

Duration of exposure:

6 h

Concentrations:

The average mass concentration of the TiO2 aerosol was 4.01 ± 1.11 mg/m3 in the nose-only chamber and 4.10 ± 1.07 mg/m3 in the whole-body chamber, respectively.

No. of animals per sex per dose:

5 animals per group. Only male rats were used

Control animals:

yes

Details on study design:

All the rats were sacrificed by overdose of pentobarbital immediately after 6 h inhalation. The wet lung weights of each rat were measured, and each right lung was used for determining the amounts of TiO2, while each left lung was used for histopathological examination

Statistics:

Analysis of variance (ANOVA) and Dunnett’s test were applied where appropriate to determine individual differences using a computer statistical package (SPSS, SPSS Inc., Chicago, IL, USA).
The amounts of TiO2 in the lungs after the inhalation were 42.6 ± 3.5 μg in the whole-body inhalation group and 46.0 ± 7.7 μg in the nose-only inhalation group. There was no statistical difference between the two groups.

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LC50

Remarks on result:

not measured/tested

Remarks:

No mortality was observed during the exposure time and histopathological examination showed no Infiltrations of inflammatory cells in the alveolar space and interstitium, fibrosis or tumorgenesis in any of the treatment groups or in the control group. Macrophages engulfed pigment-like components in both whole-body and nose-only exposure were the only observation in treatment groups.

Mortality:

None observed

Body weight:

Before the exposure, the body weights were almost the same in the three groups. After the exposure, that in the nose-only inhalation group was less, but the difference was not significant.

Gross pathology:

Infiltrations of inflammatory cells in the alveolar space and interstitium, fibrosis and tumorigenesis were not observed in any of the three groups. Macrophages engulfed pigment-like components in both whole-body and nose-only exposure

Applicant's summary and conclusion

Conclusions:

A whole-body inhalation study and a nose-only inhalation study of the same TiO2 nanoparticles in almost the same experimental conditions was carried out and compared the particle deposition and histopathological changes in the lung. The two inhalation studies yielded almost the same results.
This study exposed rate for 6 hours at concentrations of 4 mg/m³ via whole body and nose only. The aim of this study was to investigate differences for the two exposure conditions. No mortality occurred and histopathological examination showed no Infiltrations of inflammatory cells in the alveolar space and interstitium, fibrosis or tumorgenesis in any of the animals. Macrophages engulfed pigment-like components in both whole-body and nose-only exposure were the only observation in treatment groups.