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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
chronic 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 did not follow any guidelines, but it provides precious infornmation on the substance toxicity profile.

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:
Powder of test substance was administrated to male rats by inhalation route for a period of 9 months.
GLP compliance:
not specified
Limit test:
no

Test material

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

Test animals

Species:
rat
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
Initial body weight of animals were about 130 g.

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
air
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
9 months.
Frequency of treatment:
4 h/day every day
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
10 mg/m3
Basis:
no data
Remarks:
Doses / Concentrations:
30 mg/m3
Basis:
no data
Remarks:
Doses / Concentrations:
200 mg/m3
Basis:
no data
Remarks:
Doses / Concentrations:
400 mg/m3
Basis:
no data
No. of animals per sex per dose:
24 rats/males/10 mg/m3
24 rats/males/30 mg/m3
24 rats/males/200 mg/m3
24 rats/males/400 mg/m3
Control animals:
no

Examinations

Observations and examinations performed and frequency:
hematic parameters was monitored one time a month.
Sacrifice and pathology:
The parameters evalutaed for establishing of potential toxicity of barium hexaferrite powder were body weight, hemoglobin values in the blood, hematocrite, glucose concentration, chloride, hydrogen sulfide groups, hypoxia, alkali reserve, peroxydase activity, catalase activity, cholinesterase activity and transaminase activity. Every organ was examinated for ascorbic acid content, further in lung collagen content was determined. After sacrifice all tissues were collected and subjected to hystological examination.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No differences were observed
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
Significant variations of hematologic values were not registered, however an increase of enzimatic activity was observed.
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
Ascorbic acid and collagen in lungs were increased in animals exposed to higher concentrations while no differences were observed for other animals.
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Heart, liver, spleen and kidneys did not present any significant alteration. Into the lung tissue hotbeds of cells and powder were evidenced in small conglomerates or isolated.
Details on results:
Based on provision and distribution of hotbeds of cells and powder could be established that repeated exposure to high concentration (200-400 mg/m3 for 9 months) of barium hexaferrite caused pneumoconiosis by inhalation route. After exposure to 10-30 mg/m3 of barium hexaferrite an accumulation of powder and cells containing powder were observed in alveolus and on alveolar pariets. For smaller concentrations of barium hexaferrite hotbeds to the initial state were shown. By means of coloration with silver nitrated a small net of argyrophil fibers was observed, it suggest a minor cellular reaction.

Effect levels

open allclose all
Dose descriptor:
NOEC
Effect level:
< 10 mg/m³ air
Based on:
test mat.
Sex:
male
Basis for effect level:
other: The critical effect is considered the pneumoconiosis.
Dose descriptor:
NOAEC
Effect level:
30 mg/m³ air
Based on:
test mat.
Sex:
male
Basis for effect level:
other: The critical effect is considered the pneumoconiosis.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
In conclusion the inhalation of barium hexaferrite powder may cause fibrogenic activity in the lungs inducing pneumoconiosis. The rate of fibrogenic process is related to the powder concentration; a NOAEC of 30 mg/m3 is identified.