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Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: A non-GLP study performed to sound scientific principles with a sufficient level of detail to assess the quality of the submitted data. Study details poorly reported.

Data source

Reference
Reference Type:
publication
Title:
Inhalation Experiments with Tantalum Oxide Dust
Author:
Nemetschek-Gansler H et al.
Year:
1975
Bibliographic source:
Pneumonologie 152: 299-309

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
10 day repeated exposure inhalation to the test material for 10 hours each day. Inbred male Sprague-Dawley rats were used. Macroscopic and microscopic analysis was performed. The nominal concentration in the inhalation chamber was 150 mg/m³.

Dust application followed the protocol set out by Polley (1963, 1965).
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Reference substance name:
tantalum pentoxide
IUPAC Name:
tantalum pentoxide
Constituent 2
Reference substance name:
1314-61-0
Cas Number:
1314-61-0
IUPAC Name:
1314-61-0
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Tantalum Oxide Dust; Ta2O5
- Physical state: powder
- Particle size: ~ 2 µm

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Housing: In groups in large cages. Individual for exposure.

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
not specified
Remarks on MMAD:
MMAD / GSD: N.A.
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
The dust atmosphere was produced by generators, where tantalum oxide compacts were constantly pushed against a rotating grinding wheel and pulverised. A constant dose and grain spectrum was formed.

EQUIPMENT
- Cleavage-channel dust-measuring instrument
- Recording dust photometer
- Tyndalloscope.

TEST CONDITIONS
- Temperature in dust channel: ~ 22ºC
- Humidity: 80-90%
- Carbon dioxide concentration: < 0.15%.
- Oxygen depletion: constantly < 1%, measured with a Draefer-Bio Marine apparatus.
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
10 hours/day
Frequency of treatment:
10 days
Doses / concentrations
Remarks:
Doses / Concentrations:
Approximately 150 mg/m³
Basis:
analytical conc.
No. of animals per sex per dose:
A total of 18 males were used in test.
Control animals:
yes

Examinations

Observations and examinations performed and frequency:
EXAMINATIONS
- Animals were sacrificed for examination at the following time points after the end of treatment:
> day 1 (3 rats)
> day 12 (3 rats)
> day 25 (3 rats)
> day 46 (2 rats)
> day 67 (2 rats)
> day 77 (2 rats)
> day 112 (3 rats)
- Clinical signs were recorded
Sacrifice and pathology:
Histopathology of lungs, quantitative dust examinations and ray bronchographs. Histology was performed using Light Microscopy Examination and Electron-Microscopic Examination.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
Physical damage caused by the dust particles.
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Physical damage caused by the dust particles.
Histopathological findings: neoplastic:
not examined
Details on results:
GROSS PATHOLOGY
Of the animals killed up to day 46 after termination of inhalation there was one animal in each group with extended hemorrhagic infarcts of both lobes. These infarcts are probably caused by a cytotoxic lesion of the alveolar capillaries caused by the enormously high dust loading.
HISTOPATHOLOGY
Light Microscope:
A dust deposition with a time-dependent tendency to fall off, both with respect to the dust deposits as well as the density of the dust in the cells. In the hemorrhagically infarcted areas, however, there was noticed a clear falling-out of dust elimination. In addition the dust was retained over a longer period than in animals which were only exposed to dust once. In those animals killed 1 day after the termination of the experiment the dust cells were irregularly spread throughout the lung that is they were found in the alveolar as well as in the intrabronchial area. There were no indications of formation of dust granulomas; the collagen content of the tissue appeared normal. The bronchial and bronchiolar ciliated epithelium showed defects of various sizes up to the day 46 after termination of the experiment. However, tissue that was withdrawn later did not show these defects. The impression is merely that of a hyperplastic reaction. In the peribronchial lymph nodes only a few dust cells of little significance were observed.
Electron Microscope:
Showed numerous monocytes in the alveolar capillaries and the alveolar septa.
No symptoms of a significant lesion of the dust cells can be seen.

Effect levels

Dose descriptor:
LOAEC
Effect level:
150 mg/m³ air (analytical)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: Particle effect in rat

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Male Sprague-Dawley rats inhaled Tantalum oxide each day for 10 hours for a period of 10 days. In some animals hemorrhagic lesions in the lung were observed up to day 46 after termination of inhalation. These lesions were reversible, since they could not be observed after day 67 in any animal.
Executive summary:

Inbred male Sprague-Dawley rats (18 males) received a repeated inhalation to Tantalum oxide for 10 hours each day over a period of 10 days. Macroscopic and microscopic analysis was performed. The analytical concentration in the inhalation chamber was 150 mg/m³. Animals were sacrificed after 12 -112 days after the last treatment in groups of 2 or 3.The results obtained, showed that Tantalum oxide does not lead to specific changes of the lung tissues. However, in some animals hemorrhagic infarcts caused by prolonged dust application were observed. These lesions were attributed to particle effects. Since the effects could not be observed after day 67 of the experiment, they are considered reversible. The LOAEC was 150 mg/m³ in rats due to particle effects.

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