Cesium potassium fluoroaluminate

Endpoint summary

Description of key information

The oral LD50 exceeds 2000 mg/kg body weight.

The inhalatory LC50 (4 hours) was determined at 1 -5 mg/L for male and female rats based on read-across from multiconstituent aluminium potassium fluoride and cesium tetrafluoroaluminate.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 16 Dec 1999 to 06 March 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study, OECD 423 compliant

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 8 weeks old)
- Weight at study initiation: Body weight variation did not exceed +/- 20% of the sex mean.
- Housing: Group housing of 3 animals per sex per cage in labelled polycarbonate cages containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany).
- Diet: Free access to standard pelleted laboratory animal diet (from Carfil Quality BVBA, Oud­ Turnhout, Belgium).
- Water (e.g. ad libitum): Free access to tap-water.
- Acclimation period: Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C
- Humidity (%): 30 - 70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours dark per day.

IN-LIFE DATES: From: 21 Dec 1999 To: 07 Jan 2000

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The formulations (w/w) were prepared within 4 hours prior to dosing. Homogeneity was accormplished to a visually acceptable level.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

The toxicity of the test substance was assessed by stepwise treatment of groups of 3 animals. The first group was treated at a dose level of 2000 mg/kg body weight. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were to be taken into account for determination of the time interval between the dose groups.

- Duration of observation period following administration: 14 days
- Body weight: Days 1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: yes. At the end of the observation period, all animals were sacrificed by asphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
- Other examinations performed: clinical signs: - Frequency of observations: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured.

Clinical signs:

No clinical signs of systemic toxicity were noted.
One male showed alopecia and scabs in the neck before commencement of the study which persisted until day 1 (scabs) or day 11 (alopecia). These findings did not interfere with the purpose of the study and were not taken into account for interpretation of the outcome of the study.

Body weight:

The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

not classified

Conclusions:

The oral LD50 value of Cesium potassium fluoroaluminate in Wistar rats was established to exceed 2000 mg/kg body weight.

Executive summary:

The acute oral toxicity of Cesium potassium fluoroaluminate was studied according to the OECD 423 guideline, under GLP conditions. Cesium potassium fluoroaluminate was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15). No mortality occurred. No clinical signs of systemic toxicity were noted.

The body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of Cesium Potassium Fluoroaluminate in Wistar rats was established to exceed 2000 mg/kg body weight. Based on this result, Cesium potassium fluoroaluminate is not harmful by ingestion according to the EC/1272/2008 CLP criteria and is not classified.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 16 Dec 1999 to 07 March 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study, OECD 423 compliant

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 8 weeks old)
- Weight at study initiation: Body weight variation did not exceed +/- 20% of the sex mean.
- Housing: Group housing of 3 animals per sex per cage in labelled polycarbonate cages containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany).
- Diet: Free access to standard pelleted laboratory animal diet (from Carfil Quality BVBA, Oud­ Turnhout, Belgium).
- Water (e.g. ad libitum): Free access to tap-water.
- Acclimation period: Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C
- Humidity (%): 30 - 70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours dark per day.

IN-LIFE DATES: From: 21 Dec 1999 To: 07 Jan 2000

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The formulations (w/w) were prepared within 4 hours prior to dosing. Homogeneity was accormplished to a visually acceptable level.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

The toxicity of the test substance was assessed by stepwise treatment of groups of 3 animals. The first group was treated at a dose level of 2000 mg/kg body weight. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were to be taken into account for determination of the time interval between the dose groups.

- Duration of observation period following administration: 14 days
- Body weight: Days 1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: yes. At the end of the observation period, all animals were sacrificed by asphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
- Other examinations performed: clinical signs: - Frequency of observations: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

Diarrhoea was noted in one female on day 1. No clinical signs were noted in the other animals.

Body weight:

The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

not classified

Conclusions:

The oral LD50 value of Cesium potassium fluoroaluminate in Wistar rats was established to exceed 2000 mg/kg body weight.

Executive summary:

The acute oral toxicity of Cesium potassium fluoroaluminate was studied according to the OECD 423 guideline, under GLP conditions. Cesium potassium fluoroaluminate was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occurred. No clinical signs of systemic toxicity were noted. The body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals. The oral LD50 value of Cesium potassium fluoroaluminate in Wistar rats was established to exceed 2000 mg/kg body weight. Based on this result, Cesium potassium fluoroaluminate is not harmful by ingestion according to the EC/1272/2008 CLP criteria and is not classified.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

GLP studies according to standard guidelines.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 5 June 2013 (Start of in-life phase) to 25 November 2013 (GLP compliance statement)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study performed according to the OECD testing guideline and GLP used for read-accross.

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:

not specified

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No. 8147, April 2011; including the most recent partial revision

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

- Expiration date of the lot/batch: 07 May 2014
- Before use the test substance was grounded with an automatic grinder (PM100, Retsch, Ochten, The Netherlands).

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Health inspection: At least prior to exposure. It was ensured that the animals were healthy and without any abnormality that might affect the study integrity.
- Age at study initiation: Young adult animals were selected (approximately 10-11 weeks old).
- Weight at study initiation: Animals used within the study were of approximately the same age and body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: none
- Housing: Group housing of five animals per sex per cage in labelled Makrolon cages (type IV; height 18 cm) containing sterilised sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
Animal husbandry on the Day of exposure : The animals were moved to the inhalation area to in order to perform the exposure. During the exposure, there was no access to food and water. After exposure, the animals were returned their cages which were placed in a fume cupboard for a short time period to allow test substance remnants to evaporate. A sheet of filter paper was used to cover the bedding material to prevent suffocation in case of bad health condition and in order to recover and to aid the clinical observations. The sheet was removed and before the end of the exposure day, the animals were returned the animal room.
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) except during exposure to the test substance.
- Water (e.g. ad libitum): Free access to tap water except during exposure to the test substance.
- Acclimation period: Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet, water, bedding and cage enrichment evaluation for contaminants and/or nutrients was performed according to facility standard procedures.
There were no findings that could interfere with the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Environmental controls for the animal room were set to maintain 18 to 24°C
- Humidity (%): a relative humidity of 40 to 70%
- Air changes (per hr): approximately 15 room air changes/hour
- Photoperiod (hrs dark / hrs light): a 12-hour light/12-hour dark cycle
Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study.

IN-LIFE DATES: From: 6 June 2013 To: 27 June 2013

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber:
The design of the exposure chamber is based on the flow past nose-only inhalation chamber (Am. Ind. Hyg Assoc. J. 44(12): 923-928, 1983). The chamber consisted of three animal sections with eight animal ports each. Each animal port had its own atmosphere inlet and exhaust outlet. The animals were placed in restraining tubes and connected to the animal ports. The number of animal sections and number of open inlets were adapted to the air flow in such a way that at each animal port the theoretical air flow was at least 1 L/min, which ensures an adequate oxygen supply to the animals. The main inlet of the test atmosphere was located at the top section and the main outlet was located at the bottom section. The direction of the flow of the test atmosphere guaranteed a freshly generated atmosphere for each individual animal.
All components of the exposure chamber in contact with the test material were made of stainless steel, glass, rubber or plastic. To avoid exposure of the personnel and contamination of the laboratory the exposure chamber was placed in a fume hood, which maintained at a slight negative pressure.

- Test atmosphere generation :
For the generation of 5 mg/L, the test substance was fed to a stream of humidified pressurized air by means of a spiral feeder (Randcastle Extrusion Systems, Cedar Grove, NJ, USA) and an air mover (type 611210-060, Foxvalve, Dover NJ, USA). The primary aerosol was let through a cyclone (allowing
large particles to settle) and diluted with pressurized air before it entered the exposure chamber. The rotation speed of the feeder was varied to obtain the desired exposure concentration. The mean total airflow used was 36 L/min.
For the generation of 1 mg/L, the test substance was fed to a stream of pressurized air using a combination of a brush feeder and air mover (AIR-VAC, Milford, CT, USA). The aerosol was passed through a cyclone, allowing larger particles to settle, before it entered the exposure chamber
(Appendix 1, Figure 1). The mean total airflow was 22 L/min.
From the exposure chamber the test atmospheres were passed through a filter before it was released to the exhaust of the fume hood.

- Method of holding animals in test chamber:
see section "details on test animals and environmental conditions".

- Method of particle size determination:
The particle size distribution was characterized twice during each exposure period. The samples were drawn (2 L/min) from the test atmosphere through a tube mounted in one of the free animal ports of the middle section of the exposure chamber. The samples were collected with an 8 stage Marple personal cascade impactor containing fiber glass filters (SKC 225-713, fiber glass, SKC Omega Specialty Division, Chelmsford, MA, USA) and a fiber glass back-up filter (SEC-290-F1, Westech, Upper Stondon, Bedfordshire, England). Amounts of test substance collected were measured gravimetrically. Subsequently the Mass Median Aerodynamic Diameter (MMAD) and the Geometric Standard Deviation (GSD) were determined.

- Temperature, humidity, pressure in air chamber:
The temperature and relative humidity were measured with a humidity and temperature indicator (E+E Elektronik, Engerwitzdorf, Austria) and were recorded after the animals were placed in the experimental set-up and at 30 minute intervals after initiation of the exposure. The probe was inserted in a tube mounted in one of the free animal ports of the middle section of the exposure chamber.
The temperature of the atmosphere during the exposures was between 21.9 and 23.0°C. The relative humidity was between 38% and 50%. These conditions were considered appropriate for this relatively short 4 hours exposure duration.

TEST ATMOSPHERE
- Brief description of analytical method used:
A total of 23 representative samples were taken for determination of the actual concentration during exposure at 5 and 1 mg/L. Samples were drawn from the test atmosphere through a tube mounted in one of the free animal ports of the middle section of the exposure chamber. Samples were drawn
through a glass fiber filter (type APFC04700, Millipore, Billerica, MA, USA). The collected amount the test substance in the air sample was measured gravimetrically. Sample volumes were measured by means of a dry gas meter (type G 1.6, Actaris Meterfabriek B.V., Dordrecht, The Netherlands).
Subsequently the time-weighted mean concentrations with the standard deviations were calculated.

It was shown during the trial generations that the opacity of the test atmosphere could not be reliably monitored by means of an aerosol monitoring system. An indication of the stability of the test atmosphere was obtained from the concentration measurements, which were equally distributed over time.

- Samples taken from breathing zone: yes

VEHICLE
No vehicle used except air.

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The Mass Median Aerodynamic Diameter (MMAD) and geometric standard deviation (gsd) were determined twice. At 5 mg/L, the MMAD was 2.1 μm (gsd 1.8) and 2.3 μm (gsd 1.9). At 1 mg/L, the MMAD was 2.8 μm (gsd 1.7) and 2.6 μm (gsd 1.6)

CLASS METHOD
- Rationale for the selection of the starting concentration: Target concentrations were based on the cut off concentration values specified in the UN and EC classification guidelines. Five animals of each sex were exposed in a limit test for 4 hours to a target concentration of the test substance of 5 mg/L. Based on the results, five additional animals of each sex were exposed to 1 mg/L.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetrically measurement

Duration of exposure:

4 h

Concentrations:

1 and 5 mg/L.

The nominal concentration was calculated by dividing the amount of test substance used by the volume of pressurized air (average air flow times exposure time) entering the exposure chamber used for exposure of the animals. Due to the small volume of the exposure chamber the equilibrium time was negligible. The volume of air was calculated from the average air flow (measured by means of thermal mass flow meters and was recorded regularly, preferably in 30 minute intervals) and the exposure time.

No. of animals per sex per dose:

5 males and 5 females (females were nulliparous and non-pregnant) per exposure level.

Control animals:

no

Details on study design:

- Treatment:
Prior to each exposure, both eyes of each rat were instilled with Opthosan (AST Farma BV, Oudewater, The Netherlands) to protect the eyes against potential irritation by the test substance. Prior to exposure the animals were restrained in polycarbonate restraining tubes; these tubes were connected to the exposure chamber. Twenty-four or Nineteen minutes after the last animal was placed the generation of the test atmosphere was started. The exposure time was 4 hours.

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:
Mortality/Viability: Twice daily. The time of death was recorded as precisely as possible.
Body weights: Days 1 (pre-administration), 2, 4, 8 and 15 and at death (if found dead or sacrificed after Day 1).

- Necropsy of survivors performed: yes
The moribund animals and animals surviving to the end of the observation period were sacrificed by an intraperitoneal injection with Euthasol ® (AST Farma BV, Oudewater, The Netherlands). All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities were recorded. Particular attention was given to any changes in the respiratory tract.

- Other examinations performed:
clinical signs during exposure: three times during exposure for mortality, behavioural signs of distress and effects on respiration.
clinical signs after exposure : On Day 1, one and three hours after exposure and once daily thereafter until Day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).

- Electronic capture data :
Observations/measurements in the study were recorded electronically using the following programs:
REES Centron Environmental Monitoring system version SQL 2.0 (REES Scientific, Trenton, NJ, USA): Environmental monitoring.
TOXDATA version 8.0 (WIL Research Europe B.V., ‘s-Hertogenbosch, The Netherlands): Mortality / Clinical signs / Body weights. Clinical signs during exposure or not defined in TOXDATA and body weights of decedent animals were recorded manually.

Statistics:

No statistical analysis was performed.

Preliminary study:

No preliminary study has been performed.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1 - < 5 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

After exposure to 5 mg/L, two animals were sacrificed on Day 2 for ethical reasons. On Day 3, one animal was found dead and the other animals were sacrificed for ethical reasons. No mortality occurred at 1 mg/L.

Clinical signs:

other: At 5 mg/L, slow breathing was noted in all animals during exposure. After exposure, lethargy, hunched posture, laboured respiration, rales, piloerection, chromodacryorrhoea and/or ptosis were seen among the animals. Gasping was seen in one female on day 2

Body weight:

Body weight loss and reduced body weight gain was seen among the animals during the first week post-exposure. All animal regained weight during the second week.

Gross pathology:

Macroscopic post mortem examination revealed abnormalities in the lungs (discolouration pale or gray-white, fluid or foamy fluid released from the bronchi, dark red foci) of three animals exposed to 5 mg/L and sacrificed on Day 2 or 3. No further abnormalities were found in any of the animals.

Test atmosphere characterization: Concentration

For the exposure to 5 mg/L, the time-weighted mean actual concentration was 5.6 ± 0.2 mg/L. The nominal concentration was 52.8 mg/L. The generation efficiency (ratio of actual and nominal concentration) was 11%. For the exposure to 1 mg/L, the time-weighted mean actual concentration was 1.2 ± 0.04 mg/L. The nominal concentration was 28 mg/L. The generation efficiency (ratio of actual and nominal concentration) was 4%.

The measurement concentrations varied over the exposure period. Variations occurred both above and below the target concentrations. The effect of these variations on the actual exposure level was taken into account by calculating the time-weighted mean concentrations and evaluating a larger number of measurements (23 samples instead of 5). Overall, it was considered that the test atmospheres were sufficiently stable to predict the toxicity of the achieved actual exposure levels. The exposures were interrupted briefly once (5 mg/L) or twice (1 mg/L) by adjustments to the generation equipment. The generation times were prolonged in order to compensate for these short interruptions.

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The inhalatory LC50, 4h value of cesium tetrafluoroaluminate in Wistar rats was established to be within the range of 1 – 5 mg/L.

Executive summary:

The acute inhalation toxicity of cesium tetrafluoroaluminate in the rat was investigated according to the OECD Testing Guideline 403 and under GLP.

Cesium tetrafluoroaluminate was administered as an aerosol by inhalation for 4 hours to one group of five male and five female Wistar rats at 5 mg/L.Based on the results, five additional animals of each sex were exposed to 1 mg/L. Animals were subjected to daily observations and determination of body weights on Days 1, 2, 4, 8 and 15 and at death. Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15).

For the exposure to 5 mg/L, the time-weighted mean actual concentration was 5.6 ± 0.2 mg/L. For the exposure to 1 mg/L, the time-weighted mean actual concentration was 1.2 ± 0.04 mg/L. The test atmospheres were considered sufficiently stable.

The Mass Median Aerodynamic Diameter (MMAD) and geometric standard deviation (gsd) were determined twice. At 5 mg/L, the MMAD was 2.1 μm (gsd 1.8) and 2.3 μm (gsd 1.9). At 1 mg/L, the MMAD was 2.8 μm (gsd 1.7) and 2.6 μm (gsd 1.6).

After exposure to 5 mg/L, two animals were sacrificed on Day 2 for ethical reasons. On Day 3, one animal was found dead and the other animals were sacrificed for ethical reasons. No mortality occurred at 1 mg/L. At 5 mg/L, slow breathing was noted in all animals during exposure. After exposure, lethargy, hunched posture, laboured respiration, rales, piloerection, chromodacryorrhoea and/or ptosis were seen among the animals. Gasping was seen in one female on day 2 only. At 1 mg/L, no abnormalities were seen during exposure. After exposure, hunched posture, laboured respiration, rales, gasping, piloerection and/or chromodacryorrhoea were seen among the animals. Dehydration was seen in two females on Days 4 and 5. All animals recovered from these signs by Day 8, except for the rales which were also seen among the animals between Days 9 and 15 (termination).

Body weight loss and reduced body weight gain was seen among the animals during the first week post-exposure. All animal regained weight during the second week.

Macroscopic post mortem examination revealed abnormalities in the lungs (discolouration pale or gray-white, fluid or foamy fluid released from the bronchi, dark red foci) of three animals exposed to 5 mg/L and sacrificed on Day 2 or 3. No further abnormalities were found in any of the animals.

 

Based on the above observations, the inhalatory LC50, 4h value of cesium tetrafluoroaluminate in Wistar rats was established to be within the range of 1 – 5 mg/L. Based on these results the test substance needs to be classified as Category 4 H332 'Harmful if inhaled' according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP compliant, non-guideline study, available as unpublished report, minor restrictions in design and/or reporting but otherwise adequate for assessment.

Qualifier:

no guideline followed

Principles of method if other than guideline:

One group of 5 male and 5 female rats was exposed to 4.92 mg/L of the test substance for 1 hour, followed by an observation period of 14 days.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Sample number: 41105734

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: Crl:CD (SD) BR
- Source: Charles River Breeding Laboratories, Portage, MI.
- Weight at study initiation: Mean of 233 g (males) and 225 g (females).
- Fasting before study: none
- Housing: individually, cage size conformed to the standards specified in DHEW Publication (NIH) 78.23
- Diet: ad libitum, Purina Certified Rodent Chow 5002, ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): within the range specified in ABC SOP's
- Humidity (%): within the range specified in ABC SOP's
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

1.3 µm

Geometric standard deviation (GSD):

1.58

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Stainless steel and glass inhalation chamber
- Exposure chamber volume: 80
- Method of holding animals in test chamber: cage
- Source and rate of air: 21.1 l/min
- System of generating particulates/aerosols: The aerosol was generated by passing a stream of air through the test article contained in a dust shaker mechanism. The resulting air-dust mixture entered the top center of the inhalation chamber and exhausted at the bottom of the chamber. A stream of additional air was added to the chamber to achieve the desired concentration and to aid in test article dispersion
- Method of particle size determination: Delron cascade impactor, model no. DCI-6
- Treatment of exhaust air: Exhausted test atmosphere was diluted prior to release to the outside atmoshpere via an exhaust blower
- Temperature, humidity, pressure in air chamber: T: 72.3 F; RH: 40.0%; P: -0.10 inches of water

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetrical analysis
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- Particle size distribution: 99.8% of the weight of the particles is contributed by particles less than or equal to 10.0 µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD: 1.30 µm / GSD: 1.58

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetrical analysis

Duration of exposure:

1 h

Concentrations:

4.92 mg/L (gravimetric concentration); 87.2 mg/L (nominal concentration)

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: During exposure: incidence of mortality and reactions displayed every 15 min. Observation period: twice daily mortality checks. Weighing: prior to exposure and on day 14
- Gross necropsy of survivors performed: yes, external surface and body orifices, cervical organs, thoracic organs, abdominal and pelvic organs, and the brain

Preliminary study:

not performed

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4.92 mg/L air

Exp. duration:

1 h

Mortality:

Four ot the test animals died during the study (1 male, 3 females)

Clinical signs:

other: Irregular breathing, poor coat quality, yellow/brown stained fur, lethargy, crusty eye, crusty nose, and crusty muzzle

Body weight:

The surviving animals exhibited body weight gains during the invenstigational period.
- Males: Day 0: 233.4 g (SD15.9), Day 14: 281.0 g (SD 28.1).
- Females: Day 0 225.0 g (SD 24.9), Day 14: 245.5 g (SD 30.4)

Gross pathology:

Abnormalities of the stomach (multifocal erosions, diffuse red brown discoloration of glandular mucosa), glandular stomach (mucosa smooth and discolored red brown), heart (diffusely pale, tan discoloration, mottling) and small intestine (dark contents) were observed in 2 males and 3 females.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The inhalatory LC50, 4h value of multiconsituent aluminium potassium fluoride in rats was established to be within the range of 1 – 5 mg/L.

Executive summary:

The acute inhalation toxicity of multiconsituent aluminium potassium fluoride in the rat was investigated in a GLP compliant, non-guideline study. Despite some minor restrictions in design and/or reporting, the study is considered as adequate for assessment.

One group of 5 male and 5 female rats was exposed whole body to a dust atmosphere of the test substance. The duration of the exposure was 1 hour followed by a 14 day observation period. The gravimetric concentration of test article in the test atmosphere was 4.92 mg/l. Particle size analysis of the exposure chamber revealed a mass median diameter of 1.30 µm and geometric standard deviation of 1.58.

Four of the test animals died during the study. Irregular breathing, poor coat quality, yellow/brown stained fur, lethargy, crusty eye, crusty nose, and crusty muzzle were observed among the test animals during the study period. Necropsies revealed no gross lesions in 5 of 10 test animals. Abnormalities of the small intestine, stomach, and heart were observed in the remaining test rats. Based on the observed mortality it can be concluded that the 1-hour LC40 of the test substance is 4.92 mg/L which would correspond to a 4-hour LC40 of 1.23 mg/l when applying Haber's rule. The 4 -hour LC50 will be slightly above this concentration.

Based on the above observations, the inhalatory LC50, 4h value of multconstituent aluminium potassium fluoride in rats was established to be within the range of 1 – 5 mg/L and therefore the test substance needs to be classified as Category 4 H332 'Harmful if inhaled' according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Quality of whole database:

GLP study according to standard guidelines.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Oral route:

Two acute oral toxicity studies according to OECD guideline 423 and under GLP conditions are available. Two different batches of cesium potassium fluoroaluminate with different concentrations cesium were used (2% and 5%, resp.). The test materials were administered at 2000 mg/kg bw by oral gavage. Animals were observed for 14 days and necropsied. No mortality occurred. No clinical signs of systemic toxicity were noted. For this reason, the oral LD50 value of Cesium potassium fluoroaluminate in Wistar rats was established to exceed 2000 mg/kg body weight in both studies.

Inhalation route:

Since no acute inhalation toxicity study is available for cesium potassium fluoroaluminate, the results from the structural analogues multiconstituent aluminium potassium fluoride and cesium tetrafluoroaluminate are used instead (for details see Read-across justification as attached in section 13).

The acute inhalation toxicity of multiconsituent aluminium potassium fluoride in the rat was investigated in a GLP compliant, non-guideline study. Despite some minor restrictions in design and/or reporting, the study is considered as adequate for assessment. One group of 5 male and 5 female rats was exposed whole body to a dust atmosphere of the test substance. The duration of the exposure was 1 hour followed by a 14 day observation period. The gravimetric concentration of test article in the test atmosphere was 4.92 mg/l. Particle size analysis of the exposure chamber revealed a mass median diameter of 1.30 µm and geometric standard deviation of 1.58. Four of the test animals died during the study. Irregular breathing, poor coat quality, yellow/brown stained fur, lethargy, crusty eye, crusty nose, and crusty muzzle were observed among the test animals during the study period. Necropsies revealed no gross lesions in 5 of 10 test animals. Abnormalities of the small intestine, stomach, and heart were observed in the remaining test rats. Based on the observed mortality it can be concluded that the 1-hour LC40 of the test substance is 4.92 mg/L which would correspond to a 4-hour LC40 of 1.23 mg/l when applying Haber's rule. The 4 -hour LC50 will be slightly above this concentration.

The acute inhalation toxicity of cesium tetrafluoroaluminate in the rat was investigated according to the OECD Testing Guideline 403 and under GLP. Cesium tetrafluoroaluminate was administered as an aerosol by inhalation for 4 hours to one group of five male and five female Wistar rats at 5 mg/L.Based on the results, five additional animals of each sex were exposed to 1 mg/L. Animals were subjected to daily observations and determination of body weights on Days 1, 2, 4, 8 and 15 and at death. Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15). After exposure to 5 mg/L, two animals were sacrificed on Day 2 for ethical reasons. On Day 3, one animal was found dead and the other animals were sacrificed for ethical reasons. No mortality occurred at 1 mg/L. At 5 mg/L, slow breathing was noted in all animals during exposure. After exposure, lethargy, hunched posture, laboured respiration, rales, piloerection, chromodacryorrhoea and/or ptosis were seen among the animals. Gasping was seen in one female on day 2 only. At 1 mg/L, no abnormalities were seen during exposure. After exposure, hunched posture, laboured respiration, rales, gasping, piloerection and/or chromodacryorrhoea were seen among the animals. Dehydration was seen in two females on Days 4 and 5. All animals recovered from these signs by Day 8, except for the rales which were also seen among the animals between Days 9 and 15 (termination).

Body weight loss and reduced body weight gain was seen among the animals during the first week post-exposure. All animal regained weight during the second week. Macroscopic post mortem examination revealed abnormalities in the lungs (discolouration pale or gray-white, fluid or foamy fluid released from the bronchi, dark red foci) of three animals exposed to 5 mg/L and sacrificed on Day 2 or 3. No further abnormalities were found in any of the animals. Based on the above observations, the inhalatory LC50, 4h value of cesium tetrafluoroaluminate in Wistar rats was established to be within the range of 1 – 5 mg/L.

Based on these results, the inhalatory LC50 (4h) value of cesium potassium fluoroaluminate in rats is also expected to fall within the range of 1 - 5 mg/L.

Dermal route:

In accordance with column 2 of REACH Annex VIII-IX, as acute toxicity studies for the oral and inhalation route are available, no study regarding the dermal route is needed.

Justification for classification or non-classification

The oral LD50 of cesium potassium fluoroaluminate is determined to be >2000 mg/kg bw in the available acute oral toxicity studies. Based on these results,classification for acute oral toxicity according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 is not needed.

In the acute inhalation studies with the read-across candidates multiconsituent aluminium potassium fluoride and cesium tetrafluoroaluminate, LC50 valus were established to fall within the range of 1 - 5 mg/L for both substances. Therefore the substance cesium potassium fluoroaluminate needs to be classified as Cat. 4, H332 'Harmful if inhaled' according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.