boron nitride (hexagonal)

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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 following US regulation for the enforcement of the "Federal Hazardous Substances Act 16 CFR 1500". Reports are not as detailed as modern protocols but include all required information. The principles and methodology used for testing are comparable to modern OECD 423 guideline. As no relevant deficiencies have been detected, the study is considered to be reliable.

Qualifier:

according to guideline

Guideline:

other: US Regulation of the Federal Hazardous Substances Act (16 CFR 1500)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Sprague-Dawley Inc.
- Age at study initiation: young
- Weight at study initiation: 211-258 g
- Fasting period before study: yes
- Housing: wire mesh suspension cages, 5 per cage
- Diet (e.g. ad libitum): purina laboratory chow
- Water (e.g. ad libitum): water ad libitum
- Acclimation period: min. 2 days

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

Route of administration:

other: esophagel intubation

Vehicle:

corn oil

Remarks:

25% (v/v)

Doses:

5 g/kg body weight, calculated by using post-fasted body weights

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observation 2,5, 4,5 and 5 hours after dosing and once each day until end of the 14 day observation period. Body weights measured on the day of dosing and at the end of 14 day period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occured

Clinical signs:

other: other: No clinical signs observed

Gross pathology:

No observations in all rats

Other findings:

None

Interpretation of results:

GHS criteria not met

Conclusions:

The results of the performed test on acute oral toxicity of hexagonal boron nitride to rats demonstrated that the LD50 is > 5000 mg/kg body weight. Hexagonal boron nitride is therefore not classified as hazardous.

Executive summary:

Two groups, each of five male/female Sprague dawly rats, were treated with the test item by oral gavage administration at a dosage of 5000 mg/kg body weight. The test item was suspended in a vehicle (corn oil) at a concentration of 25% (v/v). All animals were allowed to acclimatise to the laboratory conditions for at least 2 days. The animals were observed for mortality/morbidity, clinical signs, body weights and examined macroscopically. All animals survived until the end of the 14-day observation period and no clinical signs were observed. At necropsy, no macroscopical findings were observed. Therefore, for hexagonal boron nitride the LD50 > 5000 mg/kg body weight and the substance should be not classified according to Annex I of Regulation (EC) 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

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.

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

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

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:

LC50 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).

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.

Interpretation of results:

GHS criteria not met

Conclusions:

In summary, based on the data available from this study the 4 h LC50 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 (LC50 > 5 mg/L).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

> 5.3 - < 6.2 mg/L air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation)

Endpoint conclusion

Endpoint conclusion:

no study available