Trialuminium bismuth hexaoxide

Endpoint summary

Description of key information

Two acute toxicity studies are available conducted by the oral and inhalation routes of administration and in accordance with appropriate OECD guidelines.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Species:

rat

Strain:

Wistar

Remarks:

RccHan: WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Oxon, UK.
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 160 to 186 g
- Fasting period before study: Yes (overnight before dosing)
- Housing: Housed in groups of up to 4 in suspended solid-floor polypropylene cages furnished with wood flakes.
- Diet (e.g. ad libitum): Teklad Global Rodent Diet
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): At least 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle.

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 mg/mL or 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: Standard vehicle

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: In the absence of data regarding the toxicity of the test item, 300 mg/kg was chosen as the starting dose.

Doses:

300 and 2000 mg/kg

No. of animals per sex per dose:

1 female at 300 mg/kg and 5 at 2000 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made 30 minutes, 1, 2 and 4 hours after dosing and then daily for up to 14 days. Individual bodyweights were recorded on Day 0 (the day of dosing), and on Days 7 and 14.
- Necropsy of survivors performed: yes

Statistics:

Not performed

Preliminary study:

One animal dosed at 300 mg/kg and another dosed at 2000 mg/kg showed no clinical signs of mortality.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed

Clinical signs:

other: No signs of systemic toxicity were noted during the observation period

Gross pathology:

No abnormalities were noted at necropsy

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test substance in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight (not classified in accordance with UN GHS and EU CLP).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

GLP compliant study and conducted in accordance with OECD guidelines.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed concentration procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

RccHan: WIST

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS (UK) Limited
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks old
- Weight at study initiation: 200 to 350 g
- Fasting period before study: No
- Housing: Housed in groups of up to 5 by sex in solid-floor polypropylene cages with stainless steel lids
- Diet (e.g. ad libitum): Free access to Teklad Global Rodent Diet (except during exposure)
- Water (e.g. ad libitum): Ad libitum except during exposure
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70% (although slightly lower that this range was determined during exposure). This was considered unavoidable and did not affect the outcome of the study.
- Air changes (per hr): At least 15
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

1.83 µm

Geometric standard deviation (GSD):

2.6

Remark on MMAD/GSD:

The resulting values (determined using a cascade impactor) were converted to probits and plotted against Log10 cut-point size. From this plot, the Mass Median Aerodynamic Diameter (MMAD) was determined (as the 50% point) and the Geometric Standard Deviation was calculated. In addition the proportion (percentage) of aerosol less than 4 μm (considered to be the inhalable fraction) was determined.

Details on inhalation exposure:

Atmosphere generation:
A dust atmosphere was produced from the test item using a SAG 410 Solid Aerosol Generator located adjacent to the exposure chamber. The SAG 410 was connected to a metered compressed air supply. Compressed air was supplied by means of an oil free compressor and passed through a water trap and respiratory quality filters before it was introduced to the SAG 410. The cylindrical exposure chamber had a volume of approximately 30 liters. The concentration within the chamber was controlled by adjusting the test item feed rate from the SAG 410. The extract from the exposure chamber passed through a ‘scrubber’ trap and was connected with a high efficiency filter to a metered exhaust system. The chamber was maintained under negative pressure. Homogeneity of the test atmosphere within the chamber was not specifically determined during this study. Chambers of the same design have been fully validated and shown to produce evenly distributed atmospheres in the animals’ breathing zone with a wide variety of test items. Prior to the start of the study, test item atmospheres were generated within the exposure chamber. During this characterization period test item input rates were varied in an attempt to achieve the required atmospheric conditions.

Exposure period:
During the exposure period, each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber ‘O’ ring. Only the nose of each animal was exposed to the test atmosphere. Following an appropriate equilibration period a single group of ten rats (five males and five females) was exposed to an atmosphere of the test item for a period of 4 hours. A target concentration of 5.0 mg/L was used for the exposure. As the mean achieved concentration was 101% of target and no deaths occurred, no further levels were required.

Exposure chamber temperature , relative humidity and oxygen concentration:
The temperature and relative humidity inside the exposure chamber were measured by an electronic thermometer/humidity meter located in a vacant port in the animals’ breathing zone of the chamber and recorded every 30 minutes throughout the 4-Hour exposure period. Oxygen levels within the exposure chamber were measured by an electronic oxygen analyzer located in a port in the animals breathing zone during the 4 Hour exposure period. The test atmosphere was generated to contain at least 19% oxygen.

Exposure chamber atmosphere generation:
The actual chamber concentration was measured at regular intervals during each exposure period. The gravimetric method used glass fiber filters placed in a filter holder. The holder was temporarily sealed in a vacant port in the exposure chamber in the animals’ breathing zone and a suitable, known volume of exposure chamber air was drawn through the filter using a vacuum pump. Each filter was weighed before and after sampling in order to calculate the weight of collected test item. The difference in the two weights, divided by the volume of atmosphere sampled, gave the actual chamber concentration. The nominal chamber concentration was calculated by dividing the mass of test item disseminated into the chamber by the total volume of air that flowed through the chamber during the exposure. The nominal concentration was 204% of the actual mean achieved atmosphere concentration and shows that keeping the aerosol airborne was straightforward.

Particle size distribution:
The particle size of the generated atmosphere inside the exposure chamber was determined three times during the exposure period using a Marple Personal Cascade Impactor. This device consisted of six impactor stages (10.4, 7.7, 4.1, 1.3, 0.9 and 0.56 μm cut points) with stainless steel collection substrates and a backup glass fiber filter, housed in an aluminum sampler. The sampler was temporarily sealed in a sampling port in the animals’ breathing zone and a suitable, known volume of exposure chamber air was drawn through it using a vacuum pump. The collection substrates and backup filter were weighed before and after sampling and the weight of test item, collected at each stage, calculated by difference. The mean amount for each stage was used to determine the cumulative amount below each cut-off point size. In this way, the proportion (%) of aerosol less than 10.4, 7.7, 4.1, 1.3, 0.9 and 0.56 μm was calculated.

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

4 h

Remarks on duration:

Standard as per OECD guideline

Concentrations:

A mean achieved atmosphere concentration of 5.07 mg/L was obtained with a standard deviation of 0.26. The nominal value was 10.34 mg/L.

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: All animals were observed for clinical signs at hourly intervals during exposure, immediately on removal from the restraining tubes at the end of exposure, 1 hour after termination of exposure and subsequently once daily for 14 days. Any evidence of overt toxicity was recorded at each observation. Individual body weights were recorded on arrival, prior to treatment on the day of exposure (Day 0) and on Days 1, 3, 7 and 14.

- Necropsy of survivors performed: At the end of the 14 day observation period the animals were killed by intravenous overdose of sodium pentobarbitone. All animals were subjected to a full external and internal examination and any macroscopic abnormalities were recorded. The respiratory tract was subjected to a detailed macroscopic examination for signs of irritancy or local toxicity.

Statistics:

None performed

Preliminary study:

Not required based on available information

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.07 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality occured in the 10 animals exposed.

Clinical signs:

other: Signs of hunched posture and pilo-erection are commonly seen in animals for short periods on removal from the chamber following 4-Hour inhalation studies. Staining of the fur by test item and wet fur are commonly recorded both during and for a short perio

Body weight:

All animals exhibited body weight losses on the first day post-exposure. Body weight gains were noted for all male animals during the remainder of the recovery period. With the exception of one female that showed no body weight gain from Days 1 to 3 post-exposure and a second female that showed no body weight gain from Days 7 to 14, body weight gains were noted for all female animals during the remainder of the recovery period.

Gross pathology:

With the exception of dark patches on the lungs noted in two males and one female no macroscopic abnormalities were detected amongst animals at necropsy.

Other findings:

None noted

Interpretation of results:

GHS criteria not met

Conclusions:

No deaths occurred in a group of ten rats exposed to a mean achieved atmosphere concentration of 5.07 mg/L for 4 hours. It was therefore considered that the acute inhalation median lethal concentration (4 hour LC50) of the test item in the Wistar strain rat was greater than 5.07 mg/L.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 070 mg/m³ air

Quality of whole database:

GLP compliant study and conducted in accordance with OECD guidelines.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

In an acute oral toxicity study, no mortality or clinical signs were noted at doses of up to 2000 mg/kg. As such the LD50 value was determined to be greater than 2000 mg/kg. In an acute inhalation toxicity study, no mortality or severe clinical signs were noted at an achieved dose of 5.07 mg/L. As such the LC50 value was determined to be greater than 5.07 mg/L. Based on these results the substance does not need to be classified in accordance with UN GHS and the CLP regulation (EC No. 1272/2008, as amended).

The applicability of STOT SE has also been considered for this substance. The substance is not classified for STOT SE Categories 1 or 2 as no relevant effects after a single exposure were noted in the available acute toxicity studies (e.g. morbidity, evidence of organ dysfunction etc.). There was also no evidence of effects linking to STOT RE 3 (respiratory tract irritation or narcotic effects). Based on the available data the substance is not classified for STOT SE in any category.