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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
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.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1990

Materials and methods

Objective of study:
excretion
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Main summary under 7.2.2 acute toxicity inhalation Haley et al 1990.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Main summary under 7.2.2 acute toxicity inhalation Haley et al 1990.
Radiolabelling:
no

Test animals

Species:
rat
Sex:
male
Details on test animals and environmental conditions:
Main summary under 7.2.2 acute toxicity inhalation Haley et al 1990.

Administration / exposure

Route of administration:
inhalation: dust
Vehicle:
unchanged (no vehicle)
Details on exposure:
Main summary under 7.2.2 acute toxicity inhalation Haley et al 1990.
Duration and frequency of treatment / exposure:
Main summary under 7.2.2 acute toxicity inhalation Haley et al 1990.
Doses / concentrations
Remarks:
Doses / Concentrations:
Main summary under 7.2.2 acute toxicity inhalation Haley et al 1990.
No. of animals per sex per dose:
Main summary under 7.2.2 acute toxicity inhalation Haley et al 1990.
Control animals:
yes
Positive control:
Main summary under 7.2.2 acute toxicity inhalation Haley et al 1990.
Details on study design:
Main summary under 7.2.2 acute toxicity inhalation Haley et al 1990.
Details on dosing and sampling:
Main summary under 7.2.2 acute toxicity inhalation Haley et al 1990.
Statistics:
Main summary under 7.2.2 acute toxicity inhalation Haley et al 1990.

Results and discussion

Preliminary studies:
Main summary under 7.2.2 acute toxicity inhalation Haley et al 1990.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no data
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.
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.