Aluminate(1-), tetrafluoro-, cesium (1:1), (T-4)-

Endpoint summary

Description of key information

Based on the read-across from cesium fluoro aluminate complex, the substance is not considered to be irritating to the skin, while it is considered to be corrosive for eyes. 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 07 July 1998 (Start of in-life phase) to 30 September 1998 (GLP compliance statement)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: 7 weeks old
- Weight at study initiation: body weights were less than 1.5 kg
At least prior to dosing, it was ensured that the animals were healthy and that the skin to be treated was intact and free from any abnormality.
- Housing: Animals were individually housed in labeled cages with perforated floors (Scanbur, Denmark) and equipped with an automatic drinking system (ITL, Bergen, The Netherlands).
- Diet: Standard laboratory rabbit diet (LKK-20, pellet diameter 4 mm, Hope Farms, Woerden, The Netherlands) approx. 100 grams per day. In addition, hay (BMI, Helmond, The Netherlands) was provided once a week.
- Water : Free access to tap water diluted with decalcified water.
- Acclimation period: at least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature: controlled at 21°C
- Humidity: controlled at 50 %
- Air changes : approximately 15 room air changes/hour
- Photoperiod : 12-hour light/12-hour dark cycle
Fluctuations from these optimal conditions were noted, but were considered as not to have affected study integrity.

IN-LIFE DATES: From: 7 to 10 July 1998.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
Amount(s) applied : Each animal was treated by dermal application of 0.5 grams of the test substance which was moistened with the vehicle (i.e. water).

VEHICLE
The powdery test substance was moistened with water (Milli-U), immediately before application, to ensure close contact with the animal's skin.
No corrections were made for the purity/composition of the test substance, since the guidelines requires a fixed amount that has to be applied.

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3 males.

Details on study design:

TEST SITE
Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm2). Whenever considered necessary the treated skin areas were reclipped at least 3 hours before the observations, to facilitate the scoring. The test item was applied to the skin of one flank, using a Scotchpak-non-woven patch of 2x3 cm. The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage.

REMOVAL OF TEST SUBSTANCE
Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using a tissue moistened with tap water and subsequently a dry tissue.

OBSERVATION AND SCORING SYSTEM:
Mortality/Viability: observation twice daily.
Toxicity: observation at least once daily.
Body Weight: day of treatment (prior to application).
Necropsy: No necropsy was performed according to protocol.
Irritation: The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance. The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of the untreated skin of each animal served as controls.
The irritation was assessed according to the following numerical scoring system. At each observation, the highest scores given were recorded:

Erythema and eschar formation:
No erythema .........................................................................................................................................0
Very slight erythema (barely perceptible) ....................................................................................... 1
Well-defined erythema ....................................................................................................................... 2
Moderate to severe erythema.............................................................................................................3
Severe erythema (beet redness) *......................................................................................................4
*. Where signs of necrosis or corrosion (injuries in depth) prevent erythema scoring, the
maximum grade for erythema (= 4) is given.

Oedema formation:
No oedema .............................................................................................................................................0
Very slight oedema (barely perceptible) ............................................................................................1
Slight oedema (edges of area well-defined by definite raising) .....................................................2
Moderate oedema (raised approximately 1 millimeter) ...................................................................3
Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure) 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Irritant / corrosive response data:

Irritation: No skin irritation was caused by 4 hours exposure to cesium fluoro aluminate complex
Corrosion: There was no evidence of a corrosive effect on the skin.
Coloration / Remnants: No staining of the treated skin by the test substance was observed.
Toxicity / Mortality : No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Other effects:

No histopathology was performed.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of the study, cesium aluminium fluoride – complex is considered to be not irritating to skin.

Executive summary:

The primary skin irritation/corrosion of Cesium aluminium fluoride - complex in the rabbit (4-hour semi-occlusive application) was investigated in a study performed according to the OECD Testing Guideline No. 404 and under GLP. Three rabbits were exposed to 0.5 grams of cesium fluoro aluminate complex, applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours after exposure. No skin irritation was observed after 4 hours exposure to cesium fluoro aluminate complex. Based on the results of the study, cesium fluoro aluminate complex is considered to be not irritating to skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 13 July 1998 (Start of in-life phase) to 30 September 1998 (GLP compliance statement)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

deviations from the maximum level of daily mean relative humidity : see additional data in results' section

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: 7 weeks old
- Weight at study initiation: body weight was less than 1.5 kg
At least prior to dosing, it was ensured that the animal was healthy and that the eyes to be treated were intact and free from any abnormality.
- Housing: Individually housed in labeled cages with perforated floors (Scanbur, Denmark) and equipped with an automatic drinking system (ITL, Bergen, The Netherlands).
- Diet: Standard laboratory rabbit diet (LKK-20, pellet diameter 4 mm, Hope Farms, Woerden, The Netherlands) approx. 100 grams per day. In addition, hay (BMI, Helmond, The Netherlands) was provided once a week.
- Water : Free access to tap water diluted with decalcified water.
- Acclimation period: at least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature: controlled at 21°C
- Humidity: controlled at 50 %
- Air changes : approximately 15 room air changes/hour
- Photoperiod : 12-hour light/12-hour dark cycle
Fluctuations from these optimal conditions were noted, but were considered as not to have affected study integrity.

IN-LIFE DATES: From: 13 July to 3 August 1998.

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 97.8 mg (approx. 0.1 ml).

VEHICLE
- Not applicable.

Duration of treatment / exposure:

Single instillation.

Observation period (in vivo):

21 days.

Number of animals or in vitro replicates:

One male.

Details on study design:

APPLICATION OF THE TEST SUBSTANCE:
On day 1, 97.8 mg of the test substance (a volume of approx. 0.1 ml) was instilled in the conjunctival sac of an eye of one animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control.

REMOVAL OF TEST SUBSTANCE
Immediately after the 24 hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes to quantitatively determine corneal epithelial damage. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area.
Immediately after fluorescein observation on day 2, the treated eye was rinsed with approx 50 mL tap water, using a velocity of flow which did not affect the eye, to remove any visible residual test substance. For reference control the other eye was also rinsed.

SCORING SYSTEM:
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7, 14 and 21 days after instillation of the test substance. The irritation scores and a description of all other (local) effects were recorded.The irritation was assessed according to the following numerical scoring system. At each observation, the highest scores given were recorded:

- CORNEAL IRRITATION
Opacity: degree of density (area most dense taken for reading)
No ulceration or opacity (may include slight dulling of normal luster) .........................................0
Scattered or diffuse areas of opacity, details of iris clearly visible................................................. 1
Easily discernible translucent area, details of iris slightly obscured...............................................2
Nacreous area, no details of iris visible, size of pupil barely discernible........................................3
Opaque cornea, iris not discernible through the opacity .................................................................4

Area of cornea involved:
No ulceration or opacity...........................................................................................................................0
One quarter or less but not zero ...........................................................................................................1
Greater than one quarter, but less than half ........................................................................................2
Greater than half, but less than three quarters ...................................................................................3
Greater than three quarters, up to whole area ....................................................................................4

- IRIS
Normal .......................................................................................................................................................0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia,
or injection, any of these or combination thereof, iris still reacting to light
(sluggish reaction is positive) ................................................................................................................1
No reaction to light, hemorrhage, gross destruction (any or all of these)......................................2

- CONJUNCTIVAL IRRITATION
Redness (refers to palpebrae and sclera, excluding cornea and iris):
Blood vessels normal ...............................................................................................................................0
Some blood vessels definitely hyperaemic (injected)..........................................................................1
Diffuse, crimson color, individual vessels not easily discernible......................................................2
Diffuse beefy red.......................................................................................................................................3

Chemosis (refers to lids and/or nictitating membranes):
No swelling ………………………………………… ....................................................................................0
Any swelling above normal (includes nictitating membranes) .........................................................1
Obvious swelling with partial eversion of lids......................................................................................2
Swelling with lids about half closed .......................................................................................................3
Swelling with lids more than half closed ...............................................................................................4

- Discharge:
No discharge (may include small amounts observed in inner canthus of normal animals) ........0
Any amount different from normal and/or lacrimation .....................................................................1
Discharge with moistening of the lids and hairs just adjacent to lids ..............................................2
Discharge with moistening of the lids and hairs (considerable area around the eye) ...................3

TOOL USED TO ASSESS SCORE:
Where standard lighting was considered inadequate for observing minor effects, eye examinations were performed using an ophthalmic examination lamp. In cases of equivocal results when comparing the treated and untreated eyes, the illustrated guide from the Consumer Product Safety Commission, Washington, D.C. 20207 was used for additional control purposes.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

2.7

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

3.3

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Irritant / corrosive response data:

Irritation
Instillation of 97.8 mg cesium fluoro aluminate complex (a volume of approximately 0.1 mL) into one eye of one rabbit resulted in marked effects on the cornea, iris and conjuctivae. The corneal injury consisted of opacity (maximum grade 2) and epithelial damage (maximum 75% of the corneal area). As a result of the corneal injury, pannus (neovascularization of the cornea) was apparent 7 days after instillation onwards. Iridic irritation grade 1 was observed which had resolved within 14 days. The irritation of the conjunctivae consisted of redness, chemosis and discharge. Reduced elasticity of the eye lids was noted 14 and 21 days after instillation. Signs of necrosis on the eyelids and nictitating membrane were apparent 7 days after instillation and persisted on the nictitating membrane at termination. In addition, corneal injury (opacity grade 1 and 25% epithelial damage), pannus and irritation of the conjunctivae persisted until termination. Remnants of the test substance were present in the eye on day 1 and 2.

Based on the degree and persistence of the corneal leasions, it was concluded that ocular corrosion had occurred by instillation of the test substance into the rabbit eye.

Other effects:

Coloration / Remnants:
Remnants of the test substance were present in the eye on Day 1. No staining of (peri) ocular tissues by the test substance was observed.

Toxicity / Mortality:
No symptoms of systemic toxicity were observed in the animal during the test period and no mortality occurred.

Table 1: Individual eye irritation scores

		Cornea			Iris	Conjunctivae			Discharge	Comments
Animal	Time after dosing	Opacity (0-4)	Area (0-4)	Fluor area (%)	(0-2)	Redness (0-3)	Chemosis (0-4)	Discol*	(0-3)
1152	1 hour	1	4		1	2 (ABC)	4 (AB)	-	2	b
	24 hours	1	4	75	1	2 (ABC)	4 (AB)	-	3	b
	48 hours	1	2	-	1	3 (A)	3 (A)	-	2	-
	72 hours	1	2	50	1	3 (AB)	3 (A)	-	2	-
	7 days	2	1	50	1	3 (AB)	3 (A)	AB	2	p
	14 days	2	1	35	0	3 (AB)	1 (ABC)	AB	1	pf
	21 days	1	1	25	0	3 (AB)	1 (A)	B	1	pf

Comments:

The test substance could only partly be removed by rinsing the treated eyes immediately after the 24 hours observation period.

b Remnants of the test substance in the eye

* Grey/white discolouration of the tissue indicated, as a sign of necrosis

p Pannus (neovascularisation of the cornea)

f Reduced elasticity of the eyelids

Score given fore:

A=Eyelids

B=Nictitating membrane

C=Sclera

Interpretation of results:

Category 1 (irreversible effects on the eye)

Conclusions:

Based on the degree and persistence of the corneal leasions, it was concluded that ocular corrosion had occurred by instillation of cesium aluminium fluoride – complex into the rabbit eye.

Executive summary:

The acute eye irritation/corrosion of cesium aluminium fluoride - complex in the rabbit was investigated in a study performed according to the OECD Testing Guideline No.405 and under GLP.

A single sample of 97.8 mg of cesium fluoro aluminate complex (a volume of approximately 0.1ml) was instilled into an eye of one rabbit. Observations were made 1, 24, 48 and 72 hours and 7, 14 and 21 days after instillation. Vocalisation was noted immediately after instillation, indicating pain. Instillation of Cesium fluoroaluminate complex resulted in marked effects on the cornea, iris and conjuctivae.

The corneal injury consisted of opacity (maximum grade 2) and epithelial damage (maximum 75% of the corneal area). As a result of the corneal injury, pannus (neovascularization of the cornea) was apparent 7 days after instillation onwards. Iridic irritation grade 1 was observed which had resolved within 14 days. The irritation of the conjunctivae consisted of redness, chemosis and discharge. Reduced elasticity of the eye lids was noted 14 and 21 days after instillation. Signs of necrosis on the eyelids and nictitating membrane were apparent 7 days after instillation and persisted on the nictitating membrane at termination. In addition, corneal injury (opacity grade 1 and 25% epithelial damage), pannus and irritation of the conjunctivae persisted until termination. Remnants of the test substance were present in the eye on day 1 and 2. Based on the degree and persistence of the corneal lesions, it was concluded that ocular corrosion had occurred by instillation of cesium aluminium fluoride - complex into the rabbit eye. Based on the results of this study, cesium aluminium fluoride - complex should be classified as category 1 with respect to eye damage/eye irritation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No skin and eye irritation studies are available on cesium tetrafluoroaluminate. However, Article 13 of the REACH legislation states that, in case no appropriate animal studies are available for assessment, information should be generated whenever possible by means other than vertebrate animal tests, i.e., applying alternative methods such as in vitro tests, QSARs, grouping and read-across. Data are available on a structural analogue, cesium fluoro aluminate complex which is a multi-constituent substance containing ca. 70% of CsAlF4 and ca. 30% of higher homological penta- and hexafluoroaluminic acids, Cs2AlF5 and Cs3AlF6. The presence of these higher homological salts is, however, not expected to alter significantly the physico-chemical and toxicological properties of cesium fluoro aluminate complex in comparison to cesium tetrafluoroaluminate.

Skin irritation

The primary skin irritation/corrosion of cesium fluoro aluminate complex in the rabbit (4-hour semi-occlusive application) was investigated in a study performed according to the OECD Testing Guideline No. 404 and under GLP. Three rabbits were exposed to 0.5 grams of cesium fluoro aluminate complex, applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours after exposure. No skin irritation was caused by 4 hours exposure to cesium fluoro aluminate complex. Based on these results, cesium tetrafluoroaluminate is also not considered to be irritating to the skin.

Eye irritation

The acute eye irritation/corrosion of cesium fluoro aluminate complex in the rabbit was investigated in a study performed according to the OECD Testing Guideline No. 405 and under GLP.

A single sample of 97.8mg of cesium fluoro aluminate complex (a volume of approximately 0.1ml) was instilled into an eye of one rabbit. Observations were made 1, 24, 48 and 72 hours and 7, 14 and 21 days after instillation. Vocalisation was noted immediately after instillation, indicating pain. Instillation of cesium fluoroaluminate complex resulted in marked effects on the cornea, iris and conjuctivae.

The corneal injury consisted of opacity (maximum grade 2) and epithelial damage (maximum 75% of the corneal area). As a result of the corneal injury, pannus (neovascularization of the cornea) was apparent 7 days after instillation onwards. Iridic irritation grade 1 was observed which had resolved within 14 days. The irritation of the conjunctivae consisted of redness, chemosis and discharge. Reduced elasticity of the eye lids was noted 14 and 21 days after instillation. Signs of necrosis on the eyelids and nictitating membrane were apparent 7 days after instillation and persisted on the nictitating membrane at termination. In addition, corneal injury (opacity grade 1 and 25% epithelial damage), pannus and irritation of the conjunctivae persisted until termination.Remnants of the test substance were present in the eye on day 1 and 2.

Based on the degree and persistence of the corneal lesions, it was concluded that ocular corrosion had occurred by instillation of cesium fluoro aluminate complex into the rabbit eye. Based on the results of this study, cesium tetrafluoroaluminate is also considered to be corrosive to eyes.

Justification for classification or non-classification

Based on the read-across with cesium fluoro aluminate complex, cesium tetrafluoroaluminate does not need to be classified for skin irritation. Based on the results of the available eye irritation study, in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, the substance has to be classified Cat. 1; H318: Causes serious eye damage.