Registration Dossier

Administrative data

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

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
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.
Justification for type of information:
The proposed analogue read-across approach has been assessed according to the RAAF and is concluded to be scientifically plausible and adequately justified by the reasoning and data presented in the read across justification uploaded in IUCLID section 13.2.
Reason / purpose:
read-across source
Specific details on test material used for the study:
- Sample number: 41105731
Species:
rabbit
Strain:
New Zealand White
Details on test animals 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

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
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.
Justification for type of information:
The proposed analogue read-across approach has been assessed according to the RAAF and is concluded to be scientifically plausible and adequately justified by the reasoning and data presented in the read across justification uploaded in IUCLID section 13.2.
Reason / purpose:
read-across source
Species:
rabbit
Strain:
New Zealand White
Details on test animals 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.
Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
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.
Justification for type of information:
The proposed analogue read-across approach has been assessed according to the RAAF and is concluded to be scientifically plausible and adequately justified by the reasoning and data presented in the read across justification uploaded in IUCLID section 13.2.
Reason / purpose:
read-across source
Species:
rabbit
Strain:
New Zealand White
Details on test animals 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:
read-across from supporting substance (structural analogue or surrogate)
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.
Justification for type of information:
The proposed analogue read-across approach has been assessed according to the RAAF and is concluded to be scientifically plausible and adequately justified by the reasoning and data presented in the read across justification uploaded in IUCLID section 13.2.
Reason / purpose:
read-across source
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:
other: 24, 48, 72 hrs
Score:
0.55
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, 72 hrs
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:
other: 24, 48, 72 hrs
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

The multiconstituent substance does not need to be classified for skin and respiratory tract irritation. Based on the results of the available eye irritation studies for the read across analogue substance PAF, 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.