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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP conform study not following any official guideline. The principles and methodology used for testing are comparable to modern OECD 42 guideline besides a lower frequency of observation of body weights which is not considered critical regarding reliability of the study. As no relevant deficiencies have been detected, the study is considered to be reliable.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report date:
1991

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
lower number of observations during observation period
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
boranylidyneamine
EC Number:
701-292-9
Cas Number:
10043-11-5
Molecular formula:
BN
IUPAC Name:
boranylidyneamine
Details on test material:
- Name of test material (as cited in study report): CPS & T 89-600 (Boron nitride UHP 2020 Powder)
- Producer: The Carborundum Company, Amherst, NY 14150, USA
- Substance type: inorganic
- Physical state: solid
- Analytical purity: < 98.5 %
- Impurities (identity and concentrations): B2O3 0.1 %, carbon 0.4 %, ammonia 90 ppm, lead 20 ppm
- Stability under test conditions: stable
- Storage condition of test material: room temperature in plastic bag
- Particle size: D50 4.3 µm

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Portage, Michigan, USA
- Age at study initiation: 47-54 days
- Weight at study initiation: male 206-223 g, female 160.-174 g
- Housing: individually in temperature and humidity-controlled rooms
- Diet (e.g. ad libitum): purina certified pelleted rodent chow #5002
- Water (e.g. ad libitum): tap water ad libitum
- Acclimatisation: 12 days

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: aerosol generation system (Test material was dispensed by a known and constant rate by an auger dust feed to an air-micrronizer (Fluid Energy, Model 0101). Dust was drawn into the micronizer by an aspirator, recirculated in the grinding chamberwhere particle-to-partivle impact reduced the size of the dust until the size was small enough to follow the air flow out of the micronizer. The resulting aerosole was piped to the exposure chamber.
- Exposure chamber volume: 54 L all glass exposure chamber
- Source and rate of air: in-house compressed-air system, flow rate 67 L/min
- Method of particle size determination: Andersen 8-stage cascade impactor. Mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) were calculated similar to Raabe (Environ. Sci. Technol., 2:1162-1167, 1978)
- Temperature, humidity, pressure in air chamber: Temp.: 75-81°F, Rel. hum.: 49-60 %, Airflow: 67 L/min, Oxygen level: 19.9-20.1 %.

TEST ATMOSPHERE
- Brief description of analytical method used: Nominal exposure concentration calculated by dividing the amount of test material used by the total volume of air passed through the chamber. Actual exposure concentration was determined using a gravimetric method. Samples of aerosol atmosphere were collected on 25 mm glass-fiber filters, held in open face filter holders, positioned in the exposure chamber. Samples were drawn through the filters at 3 L/min for 2 minutes. Each filter was weighed prior to and again after sample collection. The concentration was calculated as the difference in filter weight, divided by the total sample volume. Four samples were collected during each exposure.

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: (Filter size and weight percent)
9 µm: 13.1 % (by weight)
5.8 µm: 27.8 % (by weight)
4.7 µm: 19.3 % (by weight)
3.3 µm: 24.5 % (by weight)
2.1 µm: 13.1 % (by weight)
1.05 µm: 1.9 % (by weight)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): Equivalent aerodynamic diameter: 5.3-8.4 µm GSD: 1.86-1.98

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration:
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric
Duration of exposure:
4 h
Concentrations:
1.1 mg/L, 5.3 mg/L and 6.3 mg/L
No. of animals per sex per dose:
5 male and 5 female per dose
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animal were observed immediately after exposure and twice daily after exposure. Body weights were recorded before exposure on day 7 and day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
LD50 values were calculated similar to Bliss (C. I. Bliss, The Determination of the Dosage-Mortality Curve from Small Numbers, Quart. J. Pharm. Pharmacol. Vol. 11, 1938).

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.3 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
< 6.2 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
Five males and 2 females exposed to 6.2 mg/L and 1 male exposed to 5.3 mg/L died during the exposure due to suffocation from accumulated test material occulding the trachea.
Clinical signs:
other: Labored breathing was the most significant pharmacotoxic sign observed and was noted in most surviving animals.
Body weight:
Body weights were depressed in animals exposed to 5.3 mg/L but were normal in animals exposed to 1.1 mg/L.
Gross pathology:
The only exposure-related abnormality noted at necropsy were test material in the trachea and pulmonary congestion. These abnormalities were only observed in animal which died.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In summary, based on the data available from this study the 4 h LD50 value for hexagonal boron nitride was between 5.3 and 6.2 mg/L. It should be noted however, that the mechanism of death was due to a mechanical occulsion of the trachea from accumulated test material which resulted in suffocation. Performance of the study was comparable to modern OECD protocols and deficiencies relevant for reliability of the study have not been detected. Therefore, it is concluded that hexagonal boron nitride does not have to be classified as acute toxic by inhalation (LD50 > 5 mg/L).