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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
other: read across from similar substance
Adequacy of study:
key study
Study period:
September 27, 1994 to October 11, 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment. Justification for Read Across will be provided in section 13.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report date:
1994

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Similar substance 1
IUPAC Name:
Similar substance 1
Details on test material:
- Physical state: soft powder blue

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Velaz Prague
- Age at study initiation: 8 weeks
- Supplier certification: declared that animals had not the external and internal parasites, pathogenic microorganisms, viruses and fungi.
- Housing: after transporting the animals were placed in polypropylene plastic nursery containers T4 (550 x 320 x 180 mm Velaz Prague), five animals each sex separately.
- Diet: fed with granulated mixture ALTROMIN 1320 (Velaz Prague) in a dose of 12 g per animals each day
- Water: drinking water without restrictions
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3°C
- Humidity: 40-60 %
- Photoperiod: 12 hours of light and 12 hours of darkness


Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
head only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: samples were dispensing by WDFU (Wright Dust Feed Unit MK2, GA 4170, L. Adams, LTD., London) to an inhalation chamber, where they w ere dispersed through the spray; the atmosphere inside the inhalation chamber was homogeneous.
- Method of holding animals in test chamber: animals were fixed in a glass tube of diameter 60 mm so that the face of the glass cylinder to interfere with the vertical axis - 250 mm in diameter- in which there was a linear dynamic atmosphere exchange at 9 l/min.
- Source and rate of air: compressed air was taken from the central distribution Synthesia. Air flow was measured continuously throughout the exposure.

TEST CONDITIONS
- The average air flow apparatus: 0.540 m3/h
- The temperature inside the apparatus: 24°C
- Relative humidity inside the apparatus: 50%
- Actual concentration: 5.16 mg/L air

TEST SUBSTANCE
- Particle size of the test substance: :
diameter 1-4 um: 78,65%
diameter 4-10 um: 16,00%
diameter 10-20 um: 4,37%
diameter >20 um: 0.98%
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
ca. 4 h
Concentrations:
5.16 mg/l air
No. of animals per sex per dose:
5 males and 5 non-pregnant females.
Control animals:
yes
Details on study design:
- Immediately after application the animals were removed from tube, placed in breeding containers and observed.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: at immediately after exposure, 7 and 14 day
- Other examinations performed: clinical diagnosis was focused on the observation of nutritional status (food intake and water), the appearance of hair and skin, visible mucous membranes, mental activity, somatomotor activity, response to stimuli, focusing on sensitization and reactivity, lacrimation, functional assessment of the respiratory, circulatory, digestive and urogenital apparatus.
- After 14 days the animals were killed and an autopsy was performed. At autopsy were examined macroscopically thoracic and abdominal organs and lungs, trachea, larynx, thymus, liver, spleen and kidneys.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
ca. 5 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: also LC0
Mortality:
During the exposure there was no mortality of animals tested.
Clinical signs:
other: other:
Body weight:
The increase of body weight of animals tested was in according to the trend of increase of control animals.
Gross pathology:
Immediately after the 14-day observation period the animals were killed . After an autopsy was performed, focusing on the overall examination of the body surface and orifices, and macroscopic examination of the thoracic, abdominal and selected organs - trachea, lungs, heart, thymus, liver, spleen and kidneys. In one male and in one female were presents haemorrhages in the lungs. In both cases, these haemorrhages were located under the pulmonary pleura. In one female were found congested kidneys
Other findings:
Potential target organs: Trachea , lungs, heart, thymus, liver , spleen and kidneys.

Any other information on results incl. tables

Observations during the exposure:

Immediately after application the animals were removed from tubes, placed in breeding containers and observed.

Motor disorders on the body,irregular breathing were recorded.

- 60 min after application:

animals presented the same symptoms of intoxication of the first observation

- 120 min after application:

animals presented the same symptoms of previous observations

- 2 days after application:

shaggy skins, different parts of the body covered by residues of the test substance,blue urine and swollen eyelids.

- 3 days after application:

in addition to the blue color of the urine were not check for any effects .

- 4 days: apart from slight blue discoloration of urine were no clinical signs of intoxication.

- From 5 to 14 days after application: during this period there were no clinical signs of intoxication.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: not specified
Conclusions:
The test item was tested for acute inhalation toxicity. During the exposure or during the 14-day observation period there was no death of animals tested.
Executive summary:

The test item was tested for acute inhalation toxicity following OECD 403. The test was performed on 10 rats WISTAR strain, that were exposed to inhalation of dust aerosol test substance for 4 hours in the inhalation chamber. The test chemical concentration was measured gravimetric method. The size of most particles ranged from 2 to 4 µm. Particle size is one of the limiting factors in the deposition of inhaled substances in different areas of the respiratory apparatus.

During the exposure or during the 14-day observation period, there was no mortality of test animals.

Clinical signs of intoxication can be described as the result of mechanically irritating dust aerosol effect on exposed mucous membranes and upper respiratory tract (HCD).

The pathological-anatomical examination showed a infiltration of lung tissue particles of the substance tested.