Reaction mass of sodium chloride and potassium chloride and trisodium hexafluoroaluminate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Remarks:

An inhalation LC50 of 4470 μg/L (SD 850 μg/L) was obtained for Sprague-Dawley rats after a 4-hour continuous whole-body exposure to synthetic cryolite ( Huntingdon Research Centre Ltd., 1993). This study was conducted in compliance to OECD TG 403.

Adequacy of study:

key study

Study period:

1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other:

Remarks:

GLP compliant, guideline study, unpublished report available, no restrictions, fully adequate for assessment

Justification for type of information:

The read-across can be performed because trisodium hexafluoroaluminate is component parts of ADS 2-5, and is the only component with possible negative effects on human health. In view of this fact, we will detail its effect, based on published studies.

Cross-reference

Reason / purpose for cross-reference:

read-across source

Remarks:

The read-across can be performed because trisodium hexafluoroaluminate is component parts of ADS 2-5, and is the only component with possible negative effects for human health

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Remarks:

An inhalation LC50 of 4470 μg/L (SD 850 μg/L) was obtained for Sprague-Dawley rats after a 4-hour continuous whole-body exposure to synthetic cryolite (Huntingdon Research Centre Ltd., 1993). This study was conducted in compliance to OECD TG 403.

Adequacy of study:

key study

Study period:

1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other:

Remarks:

GLP compliant, guideline study, unpublished report available, no restrictions, fully adequate for assessment

Justification for type of information:

The read-across can be performed because trisodium hexafluoroaluminate is component parts of ADS 2-5, and is the only component with possible negative effects on human health. In view of this fact, we will detail its effect, based on published studies.

Reason / purpose for cross-reference:

read-across source

Remarks:

The read-across can be performed because trisodium hexafluoroaluminate is component parts of ADS 2-5, and is the only component with possible negative effects for human health

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

traditional method

Specific details on test material used for the study:

Name of test material (as cited in study report): cryolite
- Colour: white
- Form: powder

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals used in this study were selected from 3 consignments of rats obatined from Charles River UK Limited, Manston Road, Margate, Kent, UK. The rats were selected in a way that males and females would be of similar bodyweight (ca. 200 g) on the day of exposure.
On arrival the rats were allocated by random design to 1 of 4 groups, each of 5 males and 5 females.
The rats were housed by sex in groups of 5 and acclimatised to laboartory conditions for at least 5 days prior to exposure.
The holding cages (35 cm x 53 cm x 25 cm height) were made of stainless steel sheet and wire mesh and were suspended on a movable rack. All rats had free access to a measured excess amount of food (SDS RM1) and tap water.
Lighting was artificial for 12 h per day, the temperature (°C) in the holding room was 18-24 and the humidity (%) in this room was: 20-65.

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

other:

Remarks:

(no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: a wright dust generator
- Exposure chamber volume: 120 litres, each chamber was divided by wire mesh partitions to provide 10 separate animal compartments
- Method of holding animals in test chamber: whole body chambers
- Source and rate of air: 25 litres per minute
- System of generating particulates/aerosols: a wright dust generator, the test atmosphere contained a particulate aerosol generated from the test substance.
- Method of particle size determination: test atmosphere was passed trough a glass elutriation column
- Temperature, humidity in air chamber: 24 °C, 46,4 % relative humidity in control group, 24 °C and 43.7 % relative humidity in 4.34 mg/l group, 23 °C and 53.0 % relative humidity in 1.33 mg/l group, 24 °C and 49.8 % relative humidity in 2.83 mg/l group.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

ca. 4 h

Concentrations:

4.34 (±0.57), 2.83 (±0.25), 1.33 (±0.10) mg/l (mean ± SD)
33.04, 19.03 and 7.79 mg/l (nominal)

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

The rats were observed continuously for signs of reaction to the test substance during exposure and at least twice daily during the observation period. The observation period was 14 days, but extended for the highest concentration to 21 days. Body weights, food and water consumption were determined daily. At the end of the observation period surviving rats were killed for macroscopic and
microscopic examination.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

4.47 mg/L air

Mortality:

At the dosage of 4.34 mg/l two male rates were found dead on Day 5. One female rat was found on Day 7. Two male rats were found dead on Day 9 and one male was found dead on Day 10 of the observation period.
At the 2.83 mg/l dosage level one male rat was found dead on Day 4 of the observation period.

Clinical signs:

other:

Remarks:

During exposure: partial closing of the eyes and exaggerated respiratory movements; During observation period: exaggerated respiratory movements or noisy respiration, lethargy, hypothermia, pilo-erection and a hunched body posture.

Body weight:

There were moderate reductions in the rate of bodyweight gain for up to 3 days in female rats exposed at 1.33 mg/l or 2.83 mg/l of air. At 4.34 mg/l of air there was a delay in weight reduction until days 4-6. Subsequently weight gain was similar tot that of control rats. In male rats there was a slight reduction in bodyweight gain for up to 2 days following exposure at 1.33 mg/l or 2.83 mg/l of air. Male
rats exposed at 4.34 mg/l continued to lose weight until the time of death.

Gross pathology:

A high lung weight to bodyweight ratio was found for all rats surviving exposure. The lung to bodyweight ratio for the majority of rats surviving exposure at 1.33, 2.83 or 4.34 mg/l was higher than the control values.
The findings for rats that died as a result of exposure to cryolite were typified by swollen and severe congestion of the lungs.

Other findings:

Food consumption
Reductions in food consumption were observed for up to 10 days in male rats exposed at 2.82 mg/l of air. Male and female rats exposed at 1.33 mg/l and 2.82 mg/l had a reduced consumption for one day following exposure. Male rats exposed at 4.34 mg/l had a reduced food consumption until time of death. Consumption was slightly reduced for 6 days in female rats at 4.34 mg/l and for 3 days in female rats exposed at 1.33 mg/l. Water consumption was variable for most test groups with no markedly reduced level of consumption except for male rats exposed at 4.34 mg/l of air.
Microscopic pathology:
- Lungs; increased alveolar macrophages, with/without alveolar septal fibrosis adjacent to alveolar ducts, sometimes with focal alveolar epithelialisation; alveolar congestion/haemorrhage; and al veolitis.
Prominent goblet cells in the bronchiolar epithelium were recorded in some rats.
Changes seen only in decedent rats included hyaline membranes with/without alveolar oedema, bronchiolar epithelial basophilia and hyperplasia and early thrombus in pulmonary artery. Pleural inflammation was seen in a single decedent rat.
Alveolar macrophages containing brown pigment were seen in a single terminal rat.
- Liver: centrilobular hepatocyte necrosis/degeneration with sinusoidal congestion was seen in ail decedent rats in at the high dose.
Prominent.mitotic frgures were seen in a single rat at the high dose killed at termination.

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

Although ADS 2-5 is harmful by inhalation, under normal conditions of production, storage, transport and use, does not constitute a danger to human health.

Conclusions:

No adverse health effects have been reported in ADS 2-5 product preparation workers or in those using this product.

Executive summary:

In a guideline-compliant rat inhalation study, a LC50 of 4470 mg/m3 was derived. No mortality and no clinical sings were observed at 1330 mg/m3.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

not specified

GLP compliance:

yes

Test type:

other: standard acute method

Limit test:

no

Test material

Test material information

impurity 1

Reference substance name:

Trisodium hexafluoroaluminate

EC Number:

237-410-6

EC Name:

Trisodium hexafluoroaluminate

Cas Number:

13775-53-6

Molecular formula:

AlF6Na3

IUPAC Name:

trisodium hexafluoroalumanetriuide

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report): Cryolite
- Substance type: slighty coloured powder
- Analytical purity: 96.9%
- Composition of test material, percentage of components: Na 31%, Al 12.6%, F 53.3%
- Storage condition of test material: room temperature

Specific details on test material used for the study:

Name of test material (as cited in study report): cryolite
- Colour: white
- Form: powder
- Partie-Nr: 2

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals used in this study were selected from 3 consignments of rats obatined from Charles River UK Limited, Manston Road, Margate, Kent, UK. The rats were selected in a way that males and females would be of similar bodyweight (ca. 200 g) on the day of exposure.
On arrival the rats were allocated by random design to 1 of 4 groups, each of 5 males and 5 females.
The rats were housed by sex in groups of 5 and acclimatised to laboartory conditions for at least 5 days prior to exposure.
The holding cages (35 cm x 53 cm x 25 cm height) were made of stainless steel sheet and wire mesh and were suspended on a movable rack. All rats had free access to a measured excess amount of food (SDS RM1) and tap water.
Lighting was artificial for 12 h per day, the temperature (°C) in the holding room was 18-24 and the humidity (%) in this room was: 20-65.

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

other:

Remarks:

(no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: a wright dust generator
- Exposure chamber volume: 120 litres, each chamber was divided by wire mesh partitions to provide 10 separate animal compartments
- Method of holding animals in test chamber: whole body chambers
- Source and rate of air: 25 litres per minute
- System of generating particulates/aerosols: a wright dust generator, the test atmosphere contained a particulate aerosol generated from the test substance.
- Method of particle size determination: test atmosphere was passed trough a glass elutriation column
- Temperature, humidity in air chamber: 24 °C, 46,4 % relative humidity in control group, 24 °C and 43.7 % relative humidity in 4.34 mg/l group, 23 °C and 53.0 % relative humidity in 1.33 mg/l group, 24 °C and 49.8 % relative humidity in 2.83 mg/l group.
TEST ATMOSPHERE
- Brief description of analytical method used: an air sample was withdrawn trough a weighed glass fibre filter mounted in an open face filter holder. The filters were removed and re-weighed. Five air samples were taken from the chamber during each exposure.
- Samples taken from breathing zone: yes
TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
Two air samples were taken during each exposure using a Marple cascade impactor. The material collected on the stages of the sampler was weighed to determine the particle size distribution of cryolite in the test atmospheres.
Particle sizes were as follows: %<1 μm --> 4.34 mg/l group: 2.2, group 3: 1.4, group 4: 8.2.
Size for 25% (μm) --> 4.34 mg/l group: 2.6, 1.33 mg/l group: 2.5, 2.83 mg/l group: 1.8.% respirable (6 μm) --> 4.34 mg/l group: 67.9, 1.33 mg/l group: 77.8, 2.83 mg/l group: 78.0.
- MMAD (Mass median aerodynamic diameter) / GSD (geometric st. dev.): 4.34 mg/l group: 4.3, 1.33 mg/l group: 3.8 and 2.83 mg/l group: 3.2 μm.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

4.34 (±0.57), 2.83 (±0.25), 1.33 (±0.10) mg/l (mean ± SD)
33.04, 19.03 and 7.79 mg/l (nominal)
MMAD and respirable fraction:
4.34 mg/l: MMAD of 4.3 μm and 67.9 % of respirable particles;
2.83 mg/l: MMAD of 3.2 μm and 78.0 % of respirable particles;
1.33 mg/l: MMAD 3.8 μm and 77.8 % of respirable particles

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

The rats were observed continuously for signs of reaction to the test substance during exposure and at least twice daily during the observation period. The observation period was 14 days, but extended for the highest concentration to 21 days. Body weights, food and water consumption were determined daily. At the end of the observation period surviving rats were killed for macroscopic and
microscopic examination.

Statistics:

The concentration of the test substance likely to cause death in 50% of exposed rats following a single 4-hour exposure was calculated by the probit method of Miller and Tainter (Miller, LC and Tainter ML. Proc. Soc. Exp. Bio. Med., 57, 261-264, 1944).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

4.47 mg/L air

Exp. duration:

4 h

Remarks on result:

other:

Remarks:

SE is 0.85 mg/L

Mortality:

At the dosage of 4.34 mg/l two male rates were found dead on Day 5. One female rat was found on Day 7. Two male rats were found dead on Day 9 and one male was found dead on Day 10 of the observation period.
At the 2.83 mg/l dosage level one male rat was found dead on Day 4 of the observation period.

Clinical signs:

other:

Remarks:

During exposure: partial closing of the eyes and exaggerated respiratory movements; During observation period: exaggerated respiratory movements or noisy respiration, lethargy, hypothermia, pilo-erection and a hunched body posture

Body weight:

There were moderate reductions in the rate of bodyweight gain for up to 3 days in female rats exposed at 1.33 mg/l or 2.83 mg/l of air. At 4.34 mg/l of air there was a delay in weight reduction until days 4-6. Subsequently weight gain was similar tot that of control rats. In male rats there was a slight reduction in bodyweight gain for up to 2 days following exposure at 1.33 mg/l or 2.83 mg/l of air. Male
rats exposed at 4.34 mg/l continued to lose weight until the time of death.

Gross pathology:

A high lung weight to bodyweight ratio was found for all rats surviving exposure. The lung to bodyweight ratio for the majority of rats surviving exposure at 1.33, 2.83 or 4.34 mg/l was higher than the control values.
The findings for rats that died as a result of exposure to cryolite were typified by swollen and severe congestion of the lungs.

Other findings:

Food consumption
Reductions in food consumption were observed for up to 10 days in male rats exposed at 2.82 m g/l of air. Male and female rats exposed at 1.33 mg/l and 2.82 mg/l had a reduced consumption for one day following exposure. Male rats exposed at 4.34 mg/l had a reduced food consumption until time of death. Consumption was slightly reduced for 6 days in female rats at 4.34 mg/l and for 3 days in female rats exposed at 1.33 mg/l. Water consumption was variable for most test groups with no markedly reduced level of consumption except for male rats exposed at 4.34 mg/l of air.
Microscopic pathology:
- Lungs; increased alveolar macrophages, with/without alveolar septal fibrosis adjacent to alveolar ducts, sometimes with focal alveolar epithelialisation; alveolar congestion/haemorrhage; and alveolitis.
Prominent goblet cells in the bronchiolar epithelium were recorded in some rats.
Changes seen only in decedent rats included hyaline membranes with/without alveolar oedema, bronchiolar epithelial basophilia and hyperplasia and early thrombus in pulmonary artery. Pleural inflammation was seen in a single decedent rat.
Alveolar macrophages containing brown pigment were seen in a single terminal rat.
- Liver: centrilobular hepatocyte necrosis/degeneration with sinusoidal congestion was seen in ail decedent rats in at the high dose.
Prominent.mitotic frgures were seen in a single rat at the high dose killed at termination.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

Although ADS 2-5 is harmful by inhalation or if swallowed, under normal conditions of production, storage, transport and use, does not constitute a danger to human health.

Conclusions:

No adverse health effects have been reported in ADS 2-5 product preparation workers or in those using this product.

Executive summary:

In a guideline-compliant rat inhalation study, a LC50 of 4470 mg/m3 was derived. No mortality and no clinical sings were observed at 1330 mg/m3.