Beryllium oxide

Respiratory sensitisation

Administrative data

Endpoint:

respiratory sensitisation: in vivo

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study is part of a larger program on BeO toxicity. The methods seem well established and solid. The number of animals in the study is a good base for statistical analysis.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1992

Materials and methods

Principles of method if other than guideline:

Inhalation study of dogs to BeO 2 years after first exposure to BeO followed by analysis of immune response of peripheral blood and lung lymphocytes.

GLP compliance:

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:

No data included in this study. It is referred to a previous study by the same group.

Test animals

Species:

dog

Strain:

Beagle

Sex:

male/female

Details on test animals or test system and environmental conditions:

The dogs used in the study had previously been exposed to BeO by inhalation. Dogs weighed 6.2-12.2 kg and were 44-85 months old before the initial exposure.
The animals were maintaned in indoor-outdoor kennel runs and observed twice daily. They were given 350 g of food daily and water ad libitum.

Test system

Route of induction exposure:

inhalation

Remarks:

nasal

Route of challenge exposure:

inhalation

Remarks:

nasal

Vehicle:

unchanged (no vehicle)

Concentration:

Animals were exposed pernasally to BeO (aerosol) to give a final lung burden of 50 μg/kg bw

No. of animals per dose:

16 dogs

Details on study design:

Animals were exposed to BeO by inhalation 2.5 years after a similar exposure. Clearance of BeO from lung, immunological assays, and histopathology/cytology were assessed.

The immune response was assessed at 0, 14, 30, 60, 90, 120, 150, 165, 180 and 210 days after exposure.

Results and discussion

Results:

Clearance of BeO:
BeO not found in lung or excreted was generally found in the skeleton. Clearance was similar to what was previously observed

Cytologic response:
The total number of cells in lavage fluid was increased in dogs receiving the second inhalation of BeO. This response was highest 60 days after exposure and then declined. The increase was primarily due to increase in lymphocytes. Neutrophil number was also significantly increased.

Immunological response:
Proliferation of blood lymphocytes and cells isolated from lavage fluid was increased in BeO exposed animals.


Pathology:
Microgranulomas and patchy granulomatous pneumonia accompanied by focal septal fibrosis around terminal bronchioles were observed. Fibrosis into the parencyma was also observed. Macrophages with BeO was often observed in the fibrotic areas. This effect was not dependent on prior exposure to BeO.

Applicant's summary and conclusion

Interpretation of results:

no data

Conclusions:

Effects on lung do not seem to be cumulative if enough time has been between exposures.

Executive summary:

Beagle dogs were subject to a repeat exposure of BeO 2.5 years after the first exposure. The dogs were exposed to BeO by inhalation to give a final lung burden of 50 μg/kg bodyweight. The immune response of peripheral blood and lymphocytes harvested by lung lavage was measured. Histologic examination of lung tissue, clearance of BeO from lung, and cytological response was assessed in exposed animals.

The effects on lung tissue was as previously observed with formation of infiltrates of lymphocytes and macrophages that progressed to formation of granulomas. Clearance of BeO was not significantly affected by prior exposure and similar to the results from the first exposure. Finally, there was a relatively weak effect on proliferation of lymphocytes from blood and lavage fluid.