Registration Dossier

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:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
The study provides toxicological and hystopatological observations after intratracheal administration of high dose of the substance. No standard guideline was followed; however, the extreme conditions of this study with no associated deaths makes futher tests not necessary.

Data source

Reference
Reference Type:
publication
Title:
Experimental pneumoconiosis due to inspiration of barium ferrite powder
Author:
Kosova LV, Gersovic EM
Year:
1972
Bibliographic source:
Gig Tr Prof Zabol. 16 (5): 41-4

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Substance was administrated by intratracheal route; then treated animals were observed for a period of 9 months.
GLP compliance:
not specified
Test type:
other:
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Description of test material reported by authors is rappresentative of barium hexaferrite.

Test animals

Species:
rat
Strain:
other: albino rats
Sex:
not specified

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
other: intratracheal administration
Vehicle:
not specified
Analytical verification of test atmosphere concentrations:
no
Remarks on duration:
single administration
Concentrations:
50 mg of test substance was given by intratracheal route
No. of animals per sex per dose:
no data
Control animals:
yes

Results and discussion

Effect levels
Sex:
not specified
Dose descriptor:
LC0
Effect level:
> 370 other: mg/kg bw
Based on:
test mat.
Remarks on result:
other: single administration
Mortality:
not observed
Clinical signs:
other: not examined
Other findings:
Pathology exam did not show any pathological alteration in liver, heart, kidney and spleen. On day 10 after administration it was observed a reaction in the lungs: into the lung parenchyma (near bronchioles and small blood vessels) were found some powder conglomerates of different size. In distinct tracts some masses of cells and powder into the alveoli and alveoli walls were observed . Initial phase of pariets thickening were visible close to hotbed.
At the 20th day after the powder administration, hodbeds appeared as more regular masses of cells in which the powder was stacked. After 2 months, some formations of regular shape were included in significant fractions of lung parenchyma and the bounder between alveoles were less visible. The main quantity of powder granules were present in giant cells. Every hotbeds penetrated in argirofile fibers which were present as big "fasciculus".
Hystological examination with Perls coloration (specific for iron), has shown iron compunds into the cytoplasm of cells in particular giant cells. The presence of iron compounds into the cell cytoplasm evidence that it's not a common powder dissolution. In some tracts of the bronchial tube, the border brush were lost and the size of globet cells were increased and enlarged.
Three months later some cross-linked hotbeds were observed in the animal lungs and a fibrotic reaction with presence of an argirofile fiber net and collagen fiber. Further a partial freeing of lungs could be suppose because on the epithelial tissue of bronchial tube single powder granules were evidenced probably due to powder secretions in the bronchial tree.
In the following months were not observed further modifications or fibrotic reactions.

Applicant's summary and conclusion

Interpretation of results:
other: STOT SE Cat 2 - lungs - by inhalation
Remarks:
Criteria used for interpretation of results: expert judgment
Conclusions:
According to Directive 67/548/EEC and to Regulation (EC) n. 1272/2008, study results indicate that the substance should not be classified for acute toxicity by inhalation route in terms of mortality, but requires STOT SE cat 2 H371 for its effects on lungs by inhalation.