Indium trichloride

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

not applicable

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Pulmonary response of Fischer 344 rats to acute nose-only inhalation of indium trichloride

Author:

Blazka ME, Tepper JS, Dixon D, Winsett DW, O'Connor RW and Luster MI.

Year:

1994

Bibliographic source:

Environ Res. 67(1):68-83

Materials and methods

Principles of method if other than guideline:

The changes in lung volume and diffusion capacity and lung inflammatory changes in Fisher 344 Rats were evaluated after 7 and 42 days post-exposure (1h exposure) of the test material

GLP compliance:

no

Test type:

other: pulmonary study

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Indium trichloride

EC Number:

233-043-0

EC Name:

Indium trichloride

Cas Number:

10025-82-8

Molecular formula:

Cl3In

IUPAC Name:

indium trichloride

Details on test material:

Name of test substance: InCl3

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Raleigh, NC
- Age at study initiation: approximately 70-80 days old
- Weight at study initiation (g): 160-200
- Housing: NI
- Diet: rat chow ad libitum
- Water: tap water ad libitum.
- Acclimation period: NI


ENVIRONMENTAL CONDITIONS
- Temperature (°C): room temperature (not specified)
- Humidity (%): NI
- Air changes (per hr): NI
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- System of generating particulates/aerosols: using a constant output atomizer by atomising solutions of 0.04, 0.22 and 2% InCl3 (w/v) in deionized water and then dehydrating the aerosol forming dry submicron particles
TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: the geometric means of the particle size distribution of the 0.2, 2.0 and 20 mg InCl3/m3 exosure concentrations were 0.075, 0.133 and 0.750 µm respectively

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

1 h

Concentrations:

0.2, 2.0 or 20 mg InCl3/m3

No. of animals per sex per dose:

8

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 7 and 42 days
- Frequency of observations and weighing:
lungs were weighed and lung volume was measured after 7 and 42 days
- Necropsy of survivors performed: no
- Other examinations performed: other: total cell number, cell differential, and protein content in the BAL fluid

Statistics:

-two-way ANOVA: cytology and metal analysis comparisons involving multiple dose groups at more than one time point. When significant f value then the means were compared by Newman-Keuls post hoc analysis
-multivariate analysis: to evaluate overall main and interactive effects from the pulmonary function and airway challenge tests
-two-way ANOVA: performed on individual variables if significant multivariate exposure-only effects or significant exposure by time interactions were found

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

other: Decrease in lung volume and diffusion capacity. Lung inflammation as evidenced by an increase in PMN number and elevated levels of biochemical markers of lung damage (reversible effects)

Effect level:

ca. 20 mg/m³ air

Based on:

test mat.

Exp. duration:

1 h

Mortality:

no data

Clinical signs:

other: pulmonary changes

Body weight:

the body weights were not significantly different from those of control rats at either time point

Gross pathology:

no data

Other findings:

none

Any other information on results incl. tables

none

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

Under the test conditions, the data indicate that inhalation of InCl3/m3 causes acute inflammatory changes in the lung. These effects were reversible and a restrictive lung lesion or persistent inflammation did not develop.

Executive summary:

A study was performed to assess the effect of indium chloride on pulmonary changes in Fisher 344 rats.

Female Fisher 344 rats were exposed for 1 h to 0.2, 2 or 20 mg/m3 InCl3 aerosols and observed for body weights, lung weights, lung volumes, diffusing capacity for carbon monoxide (DLco), cellularity and differential of bronchoalveolar lavage (BAL) fluid and biochemical markers as fibronectin and tumor necrosis factor alfa.

Under the test conditions, exposure to 0.2 mg InCl3 was capable of initiating an inflammatory response. Seven days following inhalation of 20 mg InCl3/m3 the total cell number, fibronectin, and TNF alfa levels in the bronchial alveolar lavage fluid were 8, 40 and 5 times higher than the control, respectively. Commensurate with the level of lung injury 7 days after exposure, an acute restrictive lung lesion and increased airway responsiveness to acetylchloline were obsered. 42 days after exposure a compensatory increase in lung volume and carbon monoxide diffusing capacity in the 20mg InCl3/m3 group sugggested recovery from the lung injury. Lung collagen levels were increased in a concentration dependent manner 42 days postexposure.

The data indicate that inhalation of InCl3/m3 causes acute inflammatory changes in the lung.