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Description of key information

In a skin irritation study with rabbits, the test item showed no irritating effects (edema and erythema score 0). Potassium cyanate is slightly irritating to the rabbit eye based on mean scores of 0.33 for cornea, 0.55 for iris, 3 for conjunctivae (redness) and 1.89 for conjunctivae (chemosis).

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:
1984-08-18 to 1984-10-02
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1984
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
other: White Russian
Details on test animals or test system and environmental conditions:
- Source: Asta-Werke, Bielefeld, Germany
- Age at study initiation: 4 - 5 months
- Weight at study initiation: 2.0 - 2.35 kg
- Housing: individually
- Diet: standardized feed (ssniff)
- Water: ad libitum
- Acclimation period: 1 day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 1
- Humidity (%): 50 - 60
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied:0.5 g of test item was moistened with 0.2 mL water.
Duration of treatment / exposure:
The exposure period was 4 hours.
Observation period:
The observation period was 1, 24, 48 and 72 hours after removing of the bandage.
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6.25 cm^2
- Type of wrap: The gauze patch was hold in contact with the skin by means of an occlusive dressing (Acrylastic)

OBSERVATION TIME POINTS
- 1, 24, 48 and 72 hours after exposure

SCORING SYSTEM:
- Method of calculation: Draize scheme
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 1/24/48/72 h
Score:
0
Irritant / corrosive response data:
none
Other effects:
- Other adverse systemic effects: none
Interpretation of results:
GHS criteria not met
Conclusions:
Potassium cyanate is considered to be not irritating to rabbit's skin.
Executive summary:

The skin irritation/corrosion potential of the test item was investigated in primary dermal irritation study accordding to OECD Guideline 404 (1984). Three females of 4-5 month old White Russian rabbits were dermally exposed to 0.5 g (moistened with 0.2 mL water) of potassium cyanate for 4 hours to the animals back. Skin reactions were recorded after 24, 48 and 72 hours after exposure and evaluated according to the method of Draize. The erythema and edema score was 0 for each of the three animals. Furthermore, no systemic effects were observed after dermal application of the test item. 

Thus, the test item is considered to be not irritating to rabbit’s 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:
1984-11-06 to 1984-12-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1981
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
84/449/EEC
Deviations:
no
Principles of method if other than guideline:
N
GLP compliance:
yes
Species:
rabbit
Strain:
other: White Russian
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Asta-Werke AG, Bielefeld, Germany
- Age at study initiation: 6-7 months
- Weight at study initiation: 2.0 - 2.45 kg
- Housing: individually
- Diet: standardized feed (ssniff)
- Water: ad libitum
- Acclimation period: 1 day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:
water
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 g per eye
Duration of treatment / exposure:
single administration (the substance were not washed out)
Observation period (in vivo):
1, 24,48 and 72 hours after application; afterwards once per day (totally 21 days)
Number of animals or in vitro replicates:
3 (1 male and 2 female)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM: Draize method

TOOL USED TO ASSESS SCORE: Cliptrix highlighter
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 2 - 5 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
2
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: expected to be reversible / no irreversible damage
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritant / corrosive response data:
One hour after application, the cornea showed scattered or diffuse areas of opacity, however, the iris was clearly visible in two animals. These changes were fully reversible within 48 hours. In two animals the iris showed moderate circumcorneal hyperaemia, which was observed for 2 or 5 days, respectively. The conjunctivae was diffuse beefy red in all three animals. One of the animals showed red fluid between day 5 and 10 after test item application. Additionally, obvious swelling, with partial eversion of lids and swelling with lids about half closed were observed in all three animals. The described findings on the conjunctivae were partially observed for more than two weeks. Redness was not fully reversible within 21 days in one of the animals.
Other effects:
- No systemic effects were observed.
- All animals showed hypersecretion with varying degrees shortly after test item application, which was observed during the whole observation period of 21 days in two animals.

Additional results:

Irritation parameter                            Basis              Time point       Results              Max score        Reversibility       

conjunctivae score (secretion)          animal#1          24/48/72 h         3                         3                     fully reversible

conjunctivae score (secretion)          animal#2          24/48/72 h         0.67                    3                     fully reversible

conjunctivae score (secretion)          animal#3          24/48/72 h         1.33                    3                     fully reversible

conjunctivae score (secretion)          mean          24/48/72 h         1.67                    3                     fully reversible

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
The test item is considered to be irritating to rabbits' eye.
Executive summary:

In a primary eye irritation study according to OECD Guideline 405 and EU Method B.5, 0.1 g of the test item in water was instilled into the conjunctival sac of the right eye of 6-7 month old White Russian rabbits (1 male, 2 females) for 72 hours. Animals then were observed for 21 days. Irritation was scored by the method of Draize.

One hour after application, the cornea showed scattered or diffuse areas of opacity, however, the iris was clearly visible in two animals. These changes were fully reversible within 48 hours. In two animals the iris showed moderate circumcorneal hyperaemia, which was observed for 2 or 5 days, respectively. The conjunctiva was diffuse beefy red in all three animals. One of the animals showed red fluid between day 5 and 10 after test item application. Additionally, obvious swelling, with partial eversion of lids and swelling with lids about half closed were observed in all three animals. The described findings on the conjunctivae were partially observed for more than two weeks. In one animal slight conjunctiva redness was still observed after 21 days. The extent of the redness decreased within the observation period of 21 days and is expected to be reversible within a few days after the observation period. Thus, no irreversible damage to the rabbit's eye is observed.

The animals’ individual mean cornea opacity score (considering readings at 24, 48 and 72 hours) was 0.0, 0.33 and 0.67 for animal 1, animal 2 and animal, respectively. The iris score (24, 48 and 72 hours) was determined to be 1.0, 0.0 and 0.67 for animal 1, animal 2 and animal 3, respectively. The mean conjunctiva score (24, 48, 72 hours) was 3.0 for each of the three animals. The mean chemosis score (24, 48 and 72 hours) was 2.67, 1.0 and 2.0 for animal 1, animal 2 and animal 3, respectively.

No systemic toxicity was observed during the whole study period.

Based on the results, the test item is considered to be irritating to rabbits’ eye.

 

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

The skin irritation/corrosion potential of the test item was investigated in primary dermal irritation study accordding to OECD Guideline 404 (1984). Three females of 4-5 month old White Russian rabbits were dermally exposed to 0.5 g (moistened with 0.2 mL water) of potassium cyanate for 4 hours to the animals back. Skin reactions were recorded after 24, 48 and 72 hours after exposure and evaluated according to the method of Draize. The erythema and edema score was 0 for each of the three animals. Furthermore, no systemic effects were observed after dermal application of the test item. 

Thus, the test item is considered to be not irritating to rabbit’s skin. 

Eye irritation

In a primary eye irritation study according to OECD Guideline 405 and EU Method B.5, 0.1 g of the test item in water was instilled into the conjunctival sac of the right eye of 6-7 month old White Russian rabbits (1 male, 2 females) for 72 hours. Animals then were observed for 21 days. Irritation was scored by the method of Draize.

The animals’ individual mean cornea opacity score (considering readings at 24, 48 and 72 hours) was 0.0, 0.33 and 0.67 for animal 1, animal 2 and animal, respectively. The iris score (24, 48 and 72 hours) was determined to be 1.0, 0.0 and 0.67 for animal 1, animal 2 and animal 3, respectively. The mean conjunctiva score (24, 48, 72 hours) was 3.0 for each of the three animals. The mean chemosis score (24, 48 and 72 hours) was 2.67, 1.0 and 2.0 for animal 1, animal 2 and animal 3, respectively.

The effects on the conjunctivae were partially observed for more than two weeks. In one animal slight conjunctiva redness was still observed after 21 days. The extent of the redness decreased within the observation period of 21 days and is expected to be reversible within a few days after the observation period. Thus, no irreversible damage to the rabbit's eye is observed. No systemic toxicity was observed during the whole study period.

Based on the results, the test item is considered to be irritating to rabbits’ eye.

 

The eye irritating potential of the test item was supported by the in vitro (HET-CAM assay) and in vivo results published by Gilleron et al. (1997).

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

Based on the available experimental data, the test item is not considered to be classified for skin irritation under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.

Based on the available experimental data, the test item is considered to be classified for eye irritation category 2 and labelled with H319 (Caused serious eye irritation) under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.

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