Reaction mass of Potassium aluminium tetrafluoride and Dipotassium aluminium pentafluoride monohydrate

Endpoint summary

Description of key information

The substance appeared to be not irritating to the skin and respiratory tract, while it induced eye irritation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP, non-guideline, some restrictions in design and/or reporting but otherwise adequate for assessment.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Test material was applied to the skin of three male and three female rabbits on two sites (one abraded, one unabraded) for 24 hours. Thirty minutes after removal and at 72 hours, dermal irritation was assessed (Draize score).

GLP compliance:

no

Specific details on test material used for the study:

- Sample number: 41105731

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Dutchland, Inc., Denver PA
- Age at study initiation: approximately 14 weeks of age
- Housing: individually in screen-bottom cages
- Diet: ad libitum, Teklad Laboratory Rabbit diet
- Water: ad libitum
- Acclimation period: at least 7 days

Type of coverage:

occlusive

Preparation of test site:

other: abraded and unabraded (hair was clipped)

Vehicle:

other: test material was moistened with 0.9% saline

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g per site, 2 sites per animal

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

3 males, 3 females

Details on study design:

TEST SITE
- Just before the test material was applied, crisscross epidermal abrasions were made on one exposed area of each rabbit to provide one abraded and one intact test site. (Abrasions were sufficiently deep to penetrate the stratum corneum, but not deep enough to penetrate to the dermal layer and cause bleeding).
- Type of wrap if used: 5.0 x 5.0 cm gauze patch secured wtih paper tape and overwrapped with Saran Wrap and Elastoplast tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): test sites washed with tap water and disposable paper towels
- Time after start of exposure: 24 hours

SCORING SYSTEM: at 24 hours and 72 hours, according to Draize technique. Primary dermal irritation index: the sum of the 24 and 72-hour primary dermal irritation scores, divided by two and rounded to the nearest tenth.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 hrs

Score:

0.2

Reversibility:

fully reversible within: 72 hrs

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 72 hrs

Score:

0

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 72 hrs

Score:

0

Max. score:

4

Remarks on result:

other: intact site

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 72 hrs

Score:

0

Max. score:

4

Remarks on result:

other: intact site

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 72 hrs

Score:

0.08

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Remarks on result:

other: abraded site

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 72 hrs

Score:

0.08

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Remarks on result:

other: abraded site

Irritant / corrosive response data:

The test material is not a primary skin irritant.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of the study, multiconstituent aluminium potassium fluoride is considered to be not irritating to skin.

Executive summary:

The primary skin irritation/corrosion of multiconstituent aluminium potassium fluoride in the rabbit was investigated in a non-guideline study. Despite some restrictions in design and/or reporting, the study is considered as adequate for assessment. Three male and three female rabbits were exposed to 0.5 grams of multiconstituent aluminium potassium fluoride. The test material was applied to two test sites (one abraded and one intact) on each rabbit for 24 hours using an occlusive dressing. After the exposure period, the patches were removed and the test sites were washed with tap water. Observations were made 30 minutes following removal and at 72 hours. No skin irritation was caused by 24 hours to multiconsituent aluminium potassium fluoride. Based on the results of the study, multiconsituent aluminium potassium fluoride is considered to be not irritating to skin

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP, non-guideline, some restrictions in design and/or reporting but otherwise adequate for assessment.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Test material was applied to the skin of three male and three female rabbits on two sites (one abraded, one unabraded) for 24 hours. Thirty minutes after removal and at 72 hours, dermal irritation was assessed (Draize score).

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Dutchland, Inc., Denver PA
- Age at study initiation: 14 weeks
- Housing: individually in screen-bottom cages
- Diet: ad libitum, Teklad Laboratory Rabbit diet
- Water: ad libitum
- Acclimation period: at least 7 days

Type of coverage:

occlusive

Preparation of test site:

other: abraded and unabraded (hair was clipped)

Vehicle:

other: test material was moistened with 0.9% saline

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g per site, 2 sites per animal

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

3 males, 3 females

Details on study design:

TEST SITE
- Just before the test material was applied, crisscross epidermal abrasions were made on one exposed area of each rabbit to provide one abraded and one intact test site. (Abrasions were sufficiently deep to penetrate the stratum corneum, but not deep enough to penetrate to the dermal layer and cause bleeding).
- Type of wrap if used: 5.0 x 5.0 cm gauze patch secrued wtih paper tape and overwrapped with Saran Wrap and Elastoplast tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): test sites washed with tap water and disposable paper towels
- Time after start of exposure: 24 hours

SCORING SYSTEM: at 24 hours and 72 hours, according to Draize technique. Primary dermal irritation index: the sum of the 24 and 72-hour primary dermal irritation scores, divided by two and rounded to the nearest tenth.

Irritation parameter:

primary dermal irritation index (PDII)

Time point:

other: 24 hrs

Score:

0.8

Reversibility:

fully reversible within: 72 hrs

Irritation parameter:

primary dermal irritation index (PDII)

Time point:

other: 72 hrs

Score:

0

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 72 hrs

Score:

0.17

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Remarks on result:

other: intact site

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 72 hrs

Score:

0

Max. score:

4

Remarks on result:

other: intact site

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 72 hrs

Score:

0.25

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Remarks on result:

other: abraded site

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 72 hrs

Score:

0.25

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Remarks on result:

other: abraded site

Irritant / corrosive response data:

The test material is not a primary skin irritant.

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP, non-guideline, some restrictions in design and/or reporting but otherwise adequate for assessment.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Test material was applied to the skin of three male and three female rabbits on two sites (one abraded, one unabraded) for 24 hours. Thirty minutes after removal and at 72 hours, dermal irritation was assessed (Draize score).

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Dutchland, Inc., Denver PA
- Age at study initiation: 14 weeks
- Housing: individually in screen-bottom cages
- Diet: ad libitum, Teklad Laboratory Rabbit diet
- Water: ad libitum
- Acclimation period: at least 7 days

Type of coverage:

occlusive

Preparation of test site:

other: abraded and unabraded (hair was clipped)

Vehicle:

other: test material was moistened with 0.9% saline

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g per site, 2 sites per animal

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

3 males, 3 females

Details on study design:

TEST SITE
- Just before the test material was applied, crisscross epidermal abrasions were made on one exposed area of each rabbit to provide one abraded and one intact test site. (Abrasions were sufficiently deep to penetrate the stratum corneum, but not deep enough to penetrate to the dermal layer and cause bleeding).
- Type of wrap if used: 5.0 x 5.0 cm gauze patch secrued wtih paper tape and overwrapped with Saran Wrap and Elastoplast tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): test sites washed with tap water and disposable paper towels
- Time after start of exposure: 24 hours

SCORING SYSTEM: at 24 hours and 72 hours, according to Draize technique. Primary dermal irritation index: the sum of the 24 and 72-hour primary dermal irritation scores, divided by two and rounded to the nearest tenth.

Irritation parameter:

primary dermal irritation index (PDII)

Time point:

other: 24 hrs

Score:

0.2

Irritation parameter:

primary dermal irritation index (PDII)

Time point:

other: 72 hrs

Score:

0.1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 72 hrs

Score:

0.08

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Remarks on result:

other: intact site

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 72 hrs

Score:

0

Max. score:

4

Remarks on result:

other: intact site

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 72 hrs

Score:

0.17

Max. score:

4

Reversibility:

not fully reversible within: 72 hrs

Remarks on result:

other: abraded site

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 72 hrs

Score:

0

Max. score:

4

Remarks on result:

other: abraded site

Irritant / corrosive response data:

The test material is not a primary skin irritant.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP, non-guideline, some restrictions in design and/or reporting but otherwise adequate for assessment.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Three male and three female rabbits received 0.07 g (0.1 ml) test material on the everted lower eyelid, with the contralateral eye serving as the untreated control. Occular irritation was assessed (Draize score) after 24, 48, 72 and 96 hours and 7, 14 and 21 days.

GLP compliance:

no

Specific details on test material used for the study:

- Sample number: 41105731

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hazleton Dutchland, Inc., Denver PA
- Age at study initiation: 14 weeks
- Housing: individually in screen-bottom cages
- Diet: ad libitum, Teklad Laboratory Rabbit Diet
- Water: ad libitum
- Acclimation period: at least 7 days

Vehicle:

unchanged (no vehicle)

Controls:

other: contralateral eye

Amount / concentration applied:

0.07 g (0.1 ml weight equivalent)

Duration of treatment / exposure:

single application

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

3 males, 3 females

Details on study design:

The eyes of the rabbits remained unflushed. Ocular irritation was assessed (Draize score) after 24, 48, 72 and 96 hours and 7, 14 and 21 days after treatment on the everted lower eyelid. The contralateral eye serving as the untreated control. At the 7-day reading, sodium fluorescein was used to aid in revealing corneal injury.

Irritation parameter:

other: Primary eye irritation score (Draize)

Basis:

mean

Time point:

other: 24 hrs

Score:

23.8

Irritation parameter:

other: Primary eye irritation score (Draize)

Basis:

mean

Time point:

other: 48 hrs

Score:

19.2

Irritation parameter:

other: Primary eye irritation score (Draize)

Basis:

mean

Time point:

other: 72 hrs

Score:

19.8

Irritation parameter:

other: Primary eye irritation score (Draize)

Basis:

mean

Time point:

other: 96 hrs

Score:

15.7

Irritation parameter:

other: Primary eye irritation score (Draize)

Basis:

mean

Time point:

other: 7 days

Score:

13.8

Irritation parameter:

other: Primary eye irritation score (Draize)

Basis:

mean

Time point:

other: 14 days

Score:

7

Irritation parameter:

other: Primary eye irritation score (Draize)

Basis:

mean

Time point:

other: 21 days

Score:

6.3

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, 72 hrs

Score:

1.22

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.55

Max. score:

2

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: scoring was not possible at 48 and 72 hours, white necrotic areas on conjunctivae were present

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Max. score:

4

Reversibility:

fully reversible within: 21 days

Remarks on result:

other: scoring was not possible at 48 and 72 hours, white necrotic areas on conjunctivae were present

Other effects:

White necrotic areas on the conjunctivae were seen in two animals at 24, 48, 72 and 96 hours and 7 days.
Pannus was observed in two animals at 7, 14 and 21 days.
One animal exhibited corneal neovascularization at day 21.

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Executive summary:

The acute eye irritation/corrosion of multiconstituent aluminium potassium fluoride in the rabbit was investigated in a non-guideline study. Despite some restrictions in design and/or reporting, the study is considered as adequate for assessment. A single sample 0.07 g (0.1 ml weight equivalent) of the finely ground test material was placed on the lower lid of one eye of three male and three female rabbits. The other eye served as the untreated control. The treated eyes were observed for ocular irritation at 24, 48, 72 and 96 hours and at 7 days after treatment. Because injury was present at 7 days, observations were continued at 14 and 21 days.

White necrotic areas on the conjunctivae were seen in two animals at 24, 48, 72 and 96 hours and 7 days. Pannus was observed in two animals at 7, 14 and 21 days. One animal exhibited corneal neovascularization at day 21. Based on the eye irritation scores, it is concluded that the multiconstituent aluminium potassium fluoride is irritating to eyes.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin irritation

Three skin irritation studies are available (Hazleton Laboratories, 1985g,h,i). Different aluminium potassium fluoride batches were tested: aluminium potassium fluoride 100 FLUX (AT-1 -KC), aluminium potassium fluoride NK FLUX (AT-2 -NK) and aluminium potassium fluoride NK FLUX (AT-3 -NL). The test substance (moistened with 0.9% saline) was applied to the skin of three male and three female rabbits on two sites (one abraded, one unabraded) for 24 hours under occlusion. Thirty minutes after removal and at 72 hours, dermal irritation was assessed (according to the Draize score). The Primary Dermal Irritation Indices (PDII) were 0.2, 0.8 and 0.2 at 24 hours and 0, 0 and 0.1 at 72 hours for aluminium potassium fluoride 100 FLUX (AT-1 -KC), aluminium potassium fluoride NK FLUX (AT-2 -NK) and aluminium potassium fluoride NK FLUX (AT-3 -NL), respectively. Furthermore, the primary skin irritation scores (erythema and edema) for both intact and abraded skin did not indicate that aluminium potassium fluoride is irritating to the skin.

Eye irritation

The acute eye irritation/corrosion of multiconstituent aluminium potassium fluoride in the rabbit was investigated in a non-guideline study (Hazleton Laboratories, 1985j). Despite some restrictions in design and/or reporting, the study is considered as adequate for assessment. Three male and three female rabbits received 0.07 g (0.1 ml) test material on the everted lower eyelid, with the contralateral eye serving as the untreated control. The eyes of the rabbits remained unflushed. Occular irritation was assessed (according to the Draize score) after 24, 48, 72 and 96 hours and 7, 14 and 21 days. The following primary eye irritation scores were reported: 24 hours: 23.8; 48 hours: 19.2; 72 hours: 19.8; 96 hours: 15.7; 7 days: 13.8; 14 days: 7; 21 days: 6.3. White necrotic areas on the conjunctivae were seen in two animals at 24, 48, 72 and 96 hours and 7 days. Pannus was observed in two animals at 7, 14 and 21 days. One animal exhibited corneal neovascularization at day 21. The mean (24, 48, 72 hrs) cornea score and iris score were 1.22 and 0.55, respectively (both not fully reversible within 21 days). No reliable conjunctivae and chemosis scoring was possible due to white necrotic areas. Based on the eye irritation scores, it is concluded that the multiconstituent aluminium potassium fluoride is irritating to eyes.

The eye irritating properties were confirmed by a GLP compliant guideline study that was performed with the monoconstituent substance potassium tetrafluoroaluminate which is the main constituent of multiconstituent aluminium potassium fluoride (RCC Ltd, 2000). The test substance was applied by instillation of 0.1 g into one eye of three NZW rabbits (1 male and 2 females) with the contralateral eye serving as the untreated control. The eyes of the rabbits remained unflushed. The eye reactions (mean values from 24 to 72 hours) consisted of grade 1.00 corneal opacity, grade 0.00 iris lesions, grade 2.00 redness of the conjunctivae and grade 1.33 chemosis of the conjunctivae. Diffuse corneal opacity was seen in all animals at the 1-hour examination and persisted through 72 hours before disappearing at 7 days (one animal), 10 days (one animal) or 21 days (one animal). Slight reduced light reflex of the iris was noted in one animal at the 1-hour examination. Hyperemic blood vessels of the conjunctivae and nictitating membrane were observed in all animals 1 hour after treatment and increased in severity through 72 hours before diminishing to clear by day 10 (one animal), 14 (one animal) or 17 (one animal). Obvious swelling of the conjunctivae and nictitating membrane with partial eversion of lids or with lids about half-closed was observed in all animals at the 1-hour reading before diminishing by day 7 (one animal), 10 (one animal) or 14 (one animal).

A red ring of blood vessels was observed in all animals above the iris at the 7-day reading and persisted in two animals at the 10-day reading before disappearing in only one animal 14 days after treatment.

The sclera was not visible in all animals at 1 hour due to the swelling. A slightly reddened sclera was observed in all animals at the 24-hour reading and increased in severity in one animal at the 48-hour reading whereas the sclera was not visible in the two other animals due to the mucous production in the treated eye. When the sclera of one animal was not visible, a moderately reddened sclera was seen in the two other animals at 72 hours. Slightly to markedly reddened sclera was observed in all animals from 7 to 17 days after treatment and still persisting on test day 21 in two animals. No staining of the treated eyes by the test item was observed. No corrosion was observed at any of the measuring intervals. All eye reactions were not clear 21 days after treatment.

Regarding the interpretation of the results, it should be noted that 0.1 g was applied instead of 0.1 ml. Furthermore, the eyes were not rinsed after 1 hour. Therefore the conditions under which this test was performed are considered ‘worst-case’ compared to the prescribed conditions in the OECD guideline. Based on the eye irritation scores for the period 24-72 hours, it is concluded that the substance is irritating to the eyes.

Based on the results of the available studies, it is concluded that the substance is irritating to the eyes.

Respiratory tract irritation

The available inhalation toxicity studies (acute toxicity, sensory irritation, respiratory tract sensitisation and repeated dose toxicity by inhalation) do not trigger classification for respiratory tract irritation.

Justification for classification or non-classification

Multiconstituent aluminium potassium fluoride does not need to be classified for skin and respiratory tract irritation. Based on the results of the available eye irritation studies, in accordance to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, the substance has to be classified as Cat. 2; H319, respectively.