Reaction mass of sodium chloride and potassium chloride and trisodium hexafluoroaluminate

Endpoint summary

Description of key information

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.
After oral administration to rats, an LD50 exceeding 5000 mg/kg bw was derived in several studies.
The acute dermal LD50 was greater than 2100 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

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

Remarks:

Regarding the oral route, no mortality was observed within an observation period of 14 days in a limit test according to OECD guideline 401 using 5 female and 5 male Sprague Dawley rats.

Adequacy of study:

key study

Study period:

1990

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GLP compliant, guideline study, unpublished report available, no restrictions, fully adequate for assessment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

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Synthetic Cryolite
powder

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Starin: Cr1:CD (SD) BR rat
- Source: Charles River Italia S.p.A.
- Age at study initiation: about 7-9 weeks
- Weight at study initiation: males 225-250 g, females 200 - 225 g
- Housing: 5 animals/sex/cage in air-conditioned rooms
- Diet (e.g. ad libitum): GLP 4RF21 pelleted diet ad libitum
- Water (e.g. ad libitum): from the municipal water main system ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): about 20/hour
- Photoperiod (hrs dark / hrs light): 12 hours

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

deionized water, administrationvolume 20 ml/kg

Doses:

5000 mg/kg bw

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: at 30 minutes, 2, 4 and 6 hours on the first day after administration and then twice a day up to termination of the observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: gross pathology, clinical signs and mortality
(since no changes were found at necropsy, histological examination was not performed)

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

No mortality was observed on animals treated at 5000 mg/kg bw (limit dose) during the post-treatment observation period

Clinical signs:

other: Some of the animals showed piloerection starting 6 hours after administration. This sign lasted up to day 5. One male rat showed diarrhea, with short duration, at the 6 hour observation. All animals achieved recovery within day 6

Gross pathology:

No appreciable macroscopic findings were observed.

Interpretation of results:

GHS criteria not met

Remarks:

In accordance to Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, classification is not necessary for acute oral toxicity based on the available data.

Conclusions:

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

Executive summary:

LD50 exceeding 5000 mg/kg bw

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

After oral administration to rats, an LD50 exceeding 5000 mg/kg bw was derived in several studies

Acute toxicity: via inhalation route

Link to relevant study records

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

4 470 mg/m³ air

Quality of whole database:

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

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 100 mg/kg bw

Quality of whole database:

The acute dermal LD50 was greater than 2100 mg/kg bw

Additional information

SODIUM CHLORIDE is not formally classified in the EU (according to Regulation EC No. 1272/2008 Annex VI, Table 3.1 and Regulation EC No. 1272/2008 Annex VI, Table 3.2).
For POTASSIUM CHLORIDE, based on the available data no classification has to be required.
For TRISODIUM HEXAFLUOROALUMINATE, in accordance to Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, classification is not necessary for acute oral and dermal toxicity based on the available data.

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.

After a 4-hour exposure to 4.34 mg/L 5/5 male and 1/5 female rats died within 10 days; after a 4-hour exposure to 2.83 mg/L 1/5 male (on day 4) and 0/5 female rats died; after an exposure to 1.33 mg/L no mortality was observed. Clinical signs during the exposure to cryolite dust were partial closing of the eyes in the highest dose, exaggerated respiratory movements in the medium group and no signs in the lower group. The majority of rats dying as a result of exposure to 4.34 mg/L cryolite showed signs of lethargy for 1-5 days prior to death. Other signs observed prior to death were hypothermia, piloerection and the adoption of a hunched posture; surviving animals recovered within 15 days of the observation period. At necropsy, a high lung weight to bodyweight ratio was found for all deceased rats and survivors. Macroscopic pathology demonstrated swollen and severe congestion of the lungs in decedents. Abnormalities seen in rats that survived the exposure were subpleural foci in the lungs and congested lungs. Histological examination was confined to the lungs, liver and kidneys (kidneys demonstrating unspecific findings): in the lungs, increased alveolar macrophages with/without alveolar septal fibrosis adjacent to alveolar ducts, sometimes with focal alveolar epithelialisation was observed in all cryolite exposed rats. There was some evidence of a dose-related effect on the severity of the observed lesions. Alveolar congestion/haemorrhage was recorded in all decedents treated with cryolite at the high and intermediate dose levels, and in 4/9 rats in the intermediate and 2/10 in the low dose groups killed at termination. A dose-related effect on severity was noted. Alveolitis was reported in 4/6 decedent rats and 1/4 terminal rats in the high dose group, 1/1 decedent and 1/9 terminal rats in the intermediate group. This change was not seen in any rat in the lower dose group. Prominent goblet cells in the bronchiolar epithelium were recorded in 2/6 decedent and 3/4 terminal rats in the high dose and in 1/9 terminal rats in the intermediate dose group. Changes seen only in decedent rats include hyaline membranes with/without alveolar edema in all high and intermediate dose rats, bronchiolar epithelium basophilia and hyperplasia in 4/6 decedents and early thrombus in pulmonary artery in 2/6 decedents in the high dose group.

This study triggers classification of cryolite with R20, 'harmful by inhalation'. Therefore, a DNEL has to be derived for acute inhalation exposure. As starting point for this derivation the concentration of 1.33 mg/L (1330 mg/m3) is taken. At this concentration alveolar congestion/haemorrhage was observed (LOAEC).

Regarding the oral route, no mortality was observed within an observation period of 14 days in a limit test according to OECD guideline 401 using 5 female and 5 male Sprague Dawley rats. The animals were treated with 5000 mg/kg bw of synthetic cryolite suspended in water. Some of the treated animals showed piloerection starting 6 hours after administration. This effect lasted up to day 5. At necropsy, no treatment related macroscopic findings were observed (RBM, 1990).

In a study compliant to OECD TG 401 using Wistar rats, an oral LD50 > 5000 mg/kg bw was derived. Cryolite was suspended in peanut oil and administered in a single dose intragastrically to 5 male and 5 female rats, using a rigid metal stomach tube. None of the animals died within an observation period of 14 days. The clinical signs observed were piloerection and increased salivation. No pathological findings were obtained after necropsy (Bayer AG, 1987).

In a screening study on acute toxicity (no details on method were provided) no mortality was observed in rats after oral administration of synthetic cryolite (purity not given) up to 2500 mg/kg bw. Five groups of 15 male rats each (strain not given) were dosed with 100, 250, 500, 1000 and 2500 mg/kg bw cryolite using cremophor as vehicle; the observation period was 14 days. Reduction of overall appearance and laboured breathing was observed in all rats dosed with 250 mg/kg bw and higher within 5 days after administration. No pathological findings were presented (Bayer AG, 1972).

For the dermal route also an acute toxicity study is available (Elars Bioresearch Laboratories, Inc., 1981). One dosage group of 2.1 g/kg bw and an untreated control group were tested concurrently. Each group contained ten rabbits (five males and five females). The test material remained in contact with the skin for 24 hours under occlusive conditions. At the end of 24 hours, the bandaging was removed and the skin wiped with gauze sponges to remove excess test material. Subsequently, the animals were observed for 14 days. No signs of systemic toxicity were observed in rabbits at a dosage of 2.1 g/kg bw. Based on histopathological results, the test material did produce evidence of mild dermal irritation and inflammation at the test site in New Zealand White rabbits. The acute dermal LD50 for cryolite was greater than 2.1 g/kg bw under the specified conditions.

Justification for classification or non-classification

Under normal conditions of production, storage, transport and use, ADS 2-5 does not constitute a danger to human health.

In accordance to Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, classification is not necessary for acute oral and dermal toxicity based on the available data.

 

After inhalation of cryolite an acute LC50 of 4.47 mg/L was estimated in rats (4 hours exposure). Therefore, classification as harmful (Xn); R20 is appropriate in accordance to Directive 67/548/EEC. Under EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, classification with H332 (Cat. 4) is applicable.