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Repeated dose toxicity: inhalation

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repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well-documented study with clear scope. Tailor-made for the purpose. Non-GLP, not following guideline.
Reason / purpose for cross-reference:
reference to same study

Data source

Reference Type:

Materials and methods

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:

Results and discussion

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

In rats the lesions induced by beryllium inhalation appear to be due to direct chemical toxicity and foreign-body type reactions. In man, chronic beryllium lung disease is an immunologically mediated granulomatous lung disease.
Executive summary:

Rats were exposed to an aerosol of metallic beryllium once during 50 minutes at a concentration of 800 mg/m3, (= 625 mg/rat) and followed up for 171 days. At the sacrifices after 3, 7, 10, 14, 31, 59, 115 and 171 days the investigated parameters were weight, macro- and micropathology of lungs, bronchoalveolar lavage (BAL) for cytology and enzymes and Be contents and clearance.

The treatment induced an increase in lung weight, acute necrotizing, haemorrhagic, exudative pneuminitis and intraalveolar fibrosis that peaked after 14 days. After 31 days, the inflammatory lesions had regressed to be replaced by minimal interstitial and intraalveolar fibrosis. Necrotizing inflammation reappeared after 59 days and progressed to chronic active inflammation after 115 days and worsened progressively, as did alveolar macrophage and epithelial hyperplasia, being severe after 171 days. Few diffusely distributed lymphocytes were present, but not associated with granulomas. In the BAL cells were elevated, mainly due to neutrophils. Lymphocytes were not increased. LDH, beta-glucuronidase and total protein levels were elevated up to day 14, and normal again at day 31. Only LDH was substantially increased again at day 59 and later. The Be-clearance was estimated to have a half life of about 240 days.

The results indicate that inhalation of beryllium metal by rats result in severe, acute chemical pneumonitis that is followed by a quiescent period of minimal inflammation and mild fibrosis. Progressive, chronic-active, fibrosing pneumonitis is observed later. The lesions appear to be due to direct chemical toxicity and foreign-body type reactions.