Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Repeated dose toxicity: inhalation

Currently viewing:

Administrative data

short-term repeated dose toxicity: inhalation
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
No information
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Justification for type of information:
see section 13 in IUCLID for read-across justification report
Reason / purpose for cross-reference:
reference to other study

Data source

Reference Type:
Pulmonary Toxicity in Mice by 2- and 13-week Inhalation Exposures to Indium-Tin Oxide and Indium Oxide Aerosols.
Nagano K, Nishizawa T, Eitaki Y, Ohnishi M, Noguchi T, Arito H and Fukushima S.
Bibliographic source:
J Occup Health 53 (3)

Materials and methods

Test guideline
according to guideline
OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
GLP compliance:
not specified
Limit test:

Test material

Constituent 1
Chemical structure
Reference substance name:
Diindium trioxide
EC Number:
EC Name:
Diindium trioxide
Cas Number:
Molecular formula:
diindium trioxide
Details on test material:
- Name of test material (as cited in study report): indium oxide (IO)
- Physical state: powder
- Analytical purity: 99.9%
- Impurities (identity and concentrations): trace amounts of tin, silica and lead

Test animals

Details on test animals or test system and environmental conditions:
- Source: Charles River Japan, Inc (Kanagawa, Japan)
- Age at study initiation: 4 wk old
- Weight at study initiation: M: 101-104 g (mean body weight per group); F: 92-94 g (mean body weight per group)
- Housing: individually in stainless-steel wire hanging cages, which were placed in a stainless steel inhalation exposure chamber
- Diet : sterilized commercial pellet diet (CRF-1, Oriental Yeast Co., Ltd, Tokyo, Japan)
- Water : sterilized water, ad libitum
- Acclimation period: 2 wk

- Temperature (°C): 20-24
- Humidity (%): 30-70
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
other: no data
Mass median aerodynamic diameter (MMAD):
>= 1.9 - <= 2.3 µm
Geometric standard deviation (GSD):
Remarks on MMAD:
MMAD range: 1.9-2.3 µm
GSD: 1.5-2.1 µm
Details on inhalation exposure:
- Exposure apparatus:
for 100mg/m3 a system was used consisting of a dust feeder equiped with an ejector, an exposure chamber and a digital dust indicator (Type AP-632T, Sibata Scientific Technology, Ltd, Tokyo, Japan)
for 10, 1 and 0.1mg/m3 a system was used consisting of the first-stage system for aerosol generation of a high concentration at 100mg/m3 and a further dilution system
- System of generating particulates/aerosols:
for 100mg/m3: drawing the powder with compressed clean air at the first ejector and introduced into the top of the exposure chamber where the filtered air had been kept flowing downward at 12 air changes/h
for 10, 1 and 0.1mg/m3: aerosol generation of the high concentration and its regulation were performed in the same manner as described above, and airflow containing the aerosol was delivered to a reservoir chamber for stabilization of the aerosol concentration. The airflow containing the aerosol was delivered to the second ejector and then introduced into the top of the exposure chambers where the filtered air had been kept flowing downward at 12 air changes/h
- Method of particle size determination: particles were collected on a filter and dissolved in a mixture solution of distilled water, hydrochloric acid and nitric acid (2:2:1 by volume ratio) at 160 °C. The resulting solution was diluted with nitric acid, and then subjected to atomic absorption spectrometry analysis (Polarized Zeeman Atomic Absorption Spectrophotometer, Z-5010)
- Particle size distribution: the material aerosol was collected with an 8-stage Andersen sampler. Using the mass of the particles on the filter collected at each stage of the Andersen sampler, mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) were determined
- Temperature, humidity, pressure in air chamber: negative pressure (-100 Pa)

- Analytical method used: the mass-equivalent concentration of the material aerosol was monitored with the digital dust indicator; aerosol concentration in the exposure chamber was monitored with the second digital dust indicator and regulated at a target concentration of 10, 1 or 0.1 mg/m3

Analytical verification of doses or concentrations:
Details on analytical verification of doses or concentrations:
Duration of treatment / exposure:
2 wk
Frequency of treatment:
6h/day, 5day/wk for 2 wk
Doses / concentrationsopen allclose all
Dose / conc.:
0.1 mg/m³ air
Dose / conc.:
1 mg/m³ air
Dose / conc.:
10 mg/m³ air
Dose / conc.:
100 mg/m³ air
No. of animals per sex per dose:
5 mice of each sex per dose
Control animals:
yes, concurrent no treatment
Details on study design:
Positive control:


Observations and examinations performed and frequency:
- Time schedule: animals were observed daily for their clinical signs and mortality

- Time schedule for examinations: weekly throughout the study periods

- Food consumption for each animal determined : weekly throughout the study periods


OTHER: sections of lung tissue were examined.
Sacrifice and pathology:
animals surviving to the end of the 2wk received complete necropsy
Other examinations:
Determination of indium concentrations in the lung and blood
Body weight, organ weight, and hematological and blood biochemical parameters were analyzed by Dunnett's test. A two tailed test was used for all statistics. a p value of 0.05 was used as the level of significance.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
no mortality observed
Body weight and weight changes:
not examined
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
effects observed, treatment-related
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
not examined
Details on results:
CLINICAL SIGNS AND MORTALITY: neither death, abnormal clinical sign, nor growth retardation occured in any group exposed to indium oxide for 2 weeks

HAEMATOLOGY: no induction of any hematological changes

ORGAN WEIGHTS: significantly increased relative lung weights in the mice of both sexes exposed to indium oxide at 10 and 100mg/m3

-test material particles were deposited separately as single particles in the lung of almost all 1, 10 and 100mg/m3 exposed mice, primarly within the alveolar macrophages. The test material particles were also deposited in the mediastinal lymph nodes (MLN) of the 10 and 100 mg/m3 Indium oxide exposed mice, and in the nasal-associated lymphoid tissue (NALT) of the nasopharyngeal duct of a few 10 and 100mg/m3 indium oxide exposed male mice
- alveolar proteinosis in the 10 and 100 mg/m3 indium oxide exposed mice
- incidences of alveolar macrophage infiltration was found in one 100mg/m3 indium oxide exposed male mouse
- infiltration of inflammatory cells was observed primarily in the 100 mg/m3 indium oxide exposed mice
- hyperplasia of alveolar epithelium was observed primarily in the 100 mg/m3 indium oxide exposed mice

Effect levels

open allclose all
Dose descriptor:
Effect level:
1 mg/m³ air
Based on:
test mat.
Basis for effect level:
other: lung effects
Dose descriptor:
Effect level:
10 mg/m³ air
Based on:
test mat.
Basis for effect level:
organ weights and organ / body weight ratios
other: lung effects

Target system / organ toxicity

Critical effects observed:
Lowest effective dose / conc.:
10 mg/m³ air
respiratory system: lower respiratory tract
Treatment related:
Dose response relationship:
Relevant for humans:

Any other information on results incl. tables


Applicant's summary and conclusion

Persistent pulmonary lesions including alveolar proteinosis and macrophage infiltration occured after 2 wk inhalation exposure of B6CRF1 mice to indium oxide.
Executive summary:

A study was conducted to determine the effects of sub-acute exposure of the test material on the respiratory system in B6CRF1 mice and to compare with previously reported in rats (Nagano et al 2011).

The test material was administered by inhalation 6 h /d and 5 d/wk for 2 wk at 0, 0.1, 1, 10 or 100 mg/m3 to groups of 5 mice/sex/dose. Blood and lung contents of indium were elevated in a dose-related manner in the indium oxide exposed mice. The indium oxide particles were deposited in the lung, mediastinal lymph node and nasal-associated lymphoid tissue. Exposures to the test material induced alveolar proteinosis, infiltrations of alveolar macrophages and inflammatory cells and alveolar epithelial hyperplasia in addition to increased lung weight. The indium oxide induced pulmonary lesions were milder in mice than those previously reported in rats.

In conclusion, persistent pulmonary lesions including alveolar proteinosis and macrophage infiltration occured after 2 wk inhalation exposure of mice to indium oxide.