Beryllium oxide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study is part of a greater project and the methods used are well established. The study addresses the endpoints properly.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1989

Materials and methods

Principles of method if other than guideline:

Exposure of Beagle dogs to BeO by inhalation with sacrifice of dogs after 8, 32, 64, 180 or 365 days for evaluation of beryllium tissue burden and histopathological analysis.

GLP compliance:

no

Test type:

other: No specific test type: Inhalation of BeO

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Automatically generated during migration to IUCLID 6, no data available

IUPAC Name:

Automatically generated during migration to IUCLID 6, no data available

Details on test material:

Radiolabeled BeO was used in the experiments (7BeO). Aqueous 7Be(OH2) was nebulized to generate 7BeO. The corresponding BeO particles were calcined at 500 or 1000 °C. The particles were resuspended in water to 10 mg/ml, nebulized, and passed through a tube furnace (150 °C) and diluted with air.

BeO calcined at either 500 or 1000C

Test animals

Species:

dog

Strain:

other: Beagle

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals ranged in age from 20-61 months and weighed from 6.2 to 12.2 kg. Animals were housed in indoor-outdoor kennel runs and observed daily. Water was available ad libitum, food available 350 gr/day.

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

The dogs were exposed to aerosolized BeO for 5-40 minutes until they achieved a lung burden of either 17 or 50 μg/kg bodyweight. The mean aerosol concentration was 28+/-9 μg BeO/ L.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

BeO aerosols sampled by cascade impactors, filters, real-time aerosol monitor. Particle size, mass concentration, and morphology was assessed using an electrostatic precipitator

Duration of exposure:

> 5 - < 40 min

Concentrations:

Aerosol concentration of 28+/-9 μg BeO/ L.

No. of animals per sex per dose:

Four animals in each group.

Control animals:

yes

Details on study design:

Beagle dogs were exposed to BeO calcined at either 500 or 1000 °C to achieve a final lung burden of either 17 or 50 ug/kg bodyweight. Animals (2) were sacrificed at the following timepoints: 8, 32, 64, 180, 365 days. Lung lavage was performed after 3, 6, 7, 11, 15, 18, and 22 months to determine lung immune response.

Statistics:

Data were analyzed descriptively rather than statistically.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

other: Concentration where an effect was seen in animals

Effect level:

ca. 28 other: μg BeO/l

Remarks on result:

other: No mortality was observed

Mortality:

None reported

Clinical signs:

other: None reported

Body weight:

No changes reported

Gross pathology:

No gross changes reported

Other findings:

-Lung lesions: perivascular and peribronchiolar infiltrates of lymphocytes and macrophages that progressed to microgranulomas accompanied by patchy granulomatous pneumonia.
-Lymphocyte numbers increased in exposed animals for 3 months following exposure
-BeO calcined at 500 °C was cleared more rapidly from the lung than BeO calcined at 1000 °C
-The effects were also more severe with BeO calcined at 500 °C

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information

Conclusions:

Dogs exposed to BeO by inhalation develop granulomatous lung lesions and increased number of lung lymphocytes. BeO calcined at 1000 °C is retained in the lung longer than BeO calcined at 500 °C.

Executive summary:

Beagle dogs were exposed to BeO calcinated at either 500 or 1000 °C by inhalation. The exposure period was between 5 and 40 minutes to achieve lung burdens of either 17 or 50 μg/kg bodyweight. Animals were sacrificed at 8, 32, 64, 180, or 365 days to determine BeO tissue burdens and histopathological examination. Animals were also subject to bronchoalveolar lavage after 3, 6, 7, 11, 15, 18, and 22 months to determine lung immune response.

In exposed animals there was an increase of granulomatous lung lesions and increase in lung lymphocytes. There was an effect of calcination temperature with BeO calcined at 500 °C producing more severe lung lesions. BeO calcined at 500 °C was also more rapidly cleared from the lung than BeO calcined at 1000 °C.