Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Skin irritation / corrosion

In an Acute Dermal Irritation Test according to OECD Guideline 404, the test item was determined to be non-irritating to skin.

Eye irritation

In an Acute Eye Irritation/Corrosion Test according to OECD Guideline 405, the test item was determined to be non-irritating to the eye.

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:
1992-01-30 to 1992-02-06
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
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: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: 12 - 16 weeks
- Weight at study initiation: 2.41 - 2.52 kg
- Housing: Housed in suspended metal cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 - 22 °C
- Humidity: 46 - 56 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL of the undiluted test material
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours after removal of the patches
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- % coverage: 100
- Type of wrap if used: BLENDERM (surgical adhesive tape) + elastic corset (TUBIGRIP) around the trunk

REMOVAL OF TEST SUBSTANCE
- Washing: Test material was removed by gentle swabbing with cotton wool soaked in diethyl ether
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
One hour after washing, 24, 48 and 72 hours

SCORING SYSTEM:
- Method of calculation: The scoring followed the scale from Draize (1959)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
48 h
Score:
2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
48 h
Score:
2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible
Irritant / corrosive response data:
Very slight to well-defined erythema was noted at all treated skin sites one hour after patch removal and at the 24 and 48-hour observations. Very slight erythema was noted at two treated skin sites at the 72-hour observation.

Slight to moderate oedema was noted at all treated skin sites one hour after patch removal with very slight to moderate oedema at the 24-hour observation. Very slight or slight oedema was noted at two treated skin sites at the 48-hour. Very slight oedema was noted at one treated skin site at the 72-hour observation.

Desquamation was noted at all treated skin sites seven days after treatment.
Other effects:
Not observed

Table: Individual mean scores for dermal irritation

following 4 -hour exposure

Skin reaction Individual Scores - Rabbit Number and Sex (Bodyweight kg)
247 Male
(2.52)
248 Male
(2.43)
252 Female
(2.41)
Erythema Formation
Mean score
1.7 1 0.7
Oedema Formation
Mean score
2 0.7 0.3
Interpretation of results:
GHS criteria not met
Conclusions:
In a GLP-compliant Acute Dermal Irritation Test according to OECD Guideline 404, the test item was determined to be non-irritating to skin.
Executive summary:

The irritancy potential of the test item was assessed in a GLP-compliant Acute Dermal Irritation Test according to OECD Guideline 404. A quantity of 0.5 mL of the undiluted test material was introduced under a 2.5 cm x 2.5 cm gauze patch and placed in position on the shorn skin. The patch was secured in position with a strip of surgical adhesive tape (approximate size: 2.5 cm x 4.0 cm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP). Four hours after application the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in diethyl ether. Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the scale from Draize (1959). In result, very slight to well-defined erythema was noted at all treated skin sites one hour after patch removal and at the 24 and 48-hour observations. Very slight erythema was noted at two treated skin sites at the 72-hour observation. Slight to moderate oedema was noted at all treated skin sites one hour after patch removal with very slight to moderate oedema at the 24-hour observation. Very slight or slight oedema was noted at two treated skin sites at the 48-hour. Very slight oedema was noted at one treated skin site at the 72-hour observation. Desquamation was noted at all treated skin sites seven days after treatment. The test material produced a primary irritation index of 2.0. No corrosive effects were observed. As the mean score for erythema and oedema for each animal from gradings at 24, 48 and 72 hours after patch removal was below the value of 2.3 and effects were fully reversible within observation period, the test item is regarded to be not a skin irritant. The study is considered to be valid.

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:
1992-02-17 to 1992-02-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: 12 to 16 weeks
- Weight at study initiation: 2.21 - 2.37 kg
- Housing: Individually housed in suspended metal cages
- Diet: Ad libitium
- Water: Ad libitium
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 -1 21 °C
- Humidity (%): 44 - 60
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours darkness
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL
- Concentration: Pure
Duration of treatment / exposure:
72. hours
Observation period (in vivo):
7 days
Duration of post- treatment incubation (in vitro):
An additional observation was made in one treated eye on day seven to assess the reversibility of the ocular effects.
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 72 hours

SCORING SYSTEM: According to Kay J.H. and Calandra, J.C., Soc. Cosmet. Che., 1962 13, 281-289.

TOOL USED TO ASSESS SCORE: Ophthalmoscope
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
48 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24 h
Score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
48 h
Score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
72 h
Score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
48 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
48 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24 h
Score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
48 h
Score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
72 h
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
48 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24 h
Score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
48 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24 h
Score:
2
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
48 h
Score:
2
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
72 h
Score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
48 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
48 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24 h
Score:
2
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
48 h
Score:
1
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
48 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
A dulling of the normal lustre of the corneal surface was noted in one treated eye one hour after treatment with areas of diffuse corneal opacity at the 24, 48 and 72-hour observations. No other adverse corneal effects were noted.

Iridial inflammation was noted in one treated eye one hour after treatment and at the 24 and 48-hour observations. No other adverse iridial effects were noted.

Minimal to moderate conjunctival irritation was noted in all treated eyes one hour after treatment and in two treated eyes at the 24-hour observation. Moderate conjunctival irritation persisted in one treated eye at the 48-hour observation with minimal conjunctival irritation at the 72-hour observation.

Treated eyes appeared normal 72 hours to 7 days after treatment.
Other effects:
No other effects observed.
Interpretation of results:
GHS criteria not met
Conclusions:
In an Acute Eye Irritation/Corrosion Test with white rabbits of the New Zealand strain according to OECD Guideline 405, the test item did not produce positive criteria in any test animal. Therefore, the test item is regarded to be not irritating to the eye.
Executive summary:

The eye irritating effect of the test item was investigated in an Acute Eye Irritation/Corrosion Test according to OECD Guideline 405 and in compliance with GLP principles. Three 12 to 16 weeks old white rabbits of the New Zealand strain (weight at study initiation: 2.21 - 2.37 kg; sex: one male, two females; acclimation period: 5 days) were treated with the undiluted test item by a single application of 0.1 mL to the non-irrigated eye. After consideration of the ocular response produced in the first treated animal, one drop of local anaesthetic (0.5% proxymetacaine hydrochloride) was instilled into both eyes of the other two animals 1 - 2 minutes before treatment in order to minimise pain on instillation of the test material. Assessment of ocular demage / irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment. Any adverse ocular effects were also noted. Examination of the eye was facilitated by use of the light source from a standard ophthalmoscope.The numerical values corresponding to each animal, tissue and observation time were recorded. An additional observation was made in one treated eye on day seven to assess the reversibility of the ocular effects. In result, a dulling of the normal lustre of the corneal surface was noted in one treated eye one hour after treatment with areas of diffuse corneal opacity at the 24, 48 and 72-hour observations. Iridial inflammation was noted in one treated eye one hour after treatment and at the 24 and 48-hour observations. No other adverse corneal or iridial effects were noted. Minimal to moderate conjunctival irritation was noted in all treated eyes one hour after treatment and in two treated eyes at the 24-hour observation. Moderate conjunctival irritation persisted in one treated eye at the 48-hour observation with minimal conjunctival irritation at the 72-hour observation. Treated eyes appeared normal 72 hours to 7 days after treatment. The mean scores for corneal opacity, iridial inflammation, conjunctival redness and conjunctival chemosis were below the value of 2 (max. 1.7). Acording to guideline, the test item did not produce positive effects in any test animal. In conclusion, the test item is regarded to be not corrosive or irritating to the eye. The test is regarded to be valid.

TEST ANIMALS

- Source:

David Percival Ltd., Moston, Sandbach, Cheshire, U.K.

- Age at study initiation: 12 to 16 weeks

- Weight at study initiation: 2.21 - 2.37 kg

- Housing:

Individually housed in suspended metal cages

- Diet: Ad libitium

- Water: Ad libitium

- Acclimation period: 5 days

TEST MATERIAL

- Amount applied: 0.1 mL

- Concentration: Pure

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation / corrosion

The irritancy potential of the test item was assessed in a GLP-compliant Acute Dermal Irritation Test according to OECD Guideline 404 (Tuffnell, 1992)). A quantity of 0.5 mL of the undiluted test material was introduced under a 2.5 cm x 2.5 cm gauze patch and placed in position on the shorn skin. The patch was secured in position with a strip of surgical adhesive tape (approximate size: 2.5 cm x 4.0 cm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP). Four hours after application the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in diethyl ether. Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the scale from Draize (1959). In result, very slight to well-defined erythema was noted at all treated skin sites one hour after patch removal and at the 24 and 48-hour observations. Very slight erythema was noted at two treated skin sites at the 72-hour observation. Slight to moderate oedema was noted at all treated skin sites one hour after patch removal with very slight to moderate oedema at the 24-hour observation. Very slight or slight oedema was noted at two treated skin sites at the 48-hour. Very slight oedema was noted at one treated skin site at the 72-hour observation. Desquamation was noted at all treated skin sites seven days after treatment. The test material produced a primary irritation index of 2.0. No corrosive effects were observed. As the mean score for erythema and oedema for each animal from gradings at 24, 48 and 72 hours after patch removal was below the value of 2.3 and effects were fully reversible within observation period, the test item is regarded to be not a skin irritant. The study is considered to be valid.

Eye irritation

The eye irritating effect of the test item was investigated in an Acute Eye Irritation/Corrosion Test according to OECD Guideline 405 and in compliance with GLP principles (Tuffnell, 1992). Three 12 to 16 weeks old white rabbits of the New Zealand strain (weight at study initiation: 2.21 - 2.37 kg; sex: one male, two females; acclimation period: 5 days) were treated with the undiluted test item by a single application of 0.1 mL to the non-irrigated eye. After consideration of the ocular response produced in the first treated animal, one drop of local anaesthetic (0.5% proxymetacaine hydrochloride) was instilled into both eyes of the other two animals 1 - 2 minutes before treatment in order to minimise pain on instillation of the test material. Assessment of ocular demage / irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment. Any adverse ocular effects were also noted. Examination of the eye was facilitated by use of the light source from a standard ophthalmoscope.The numerical values corresponding to each animal, tissue and observation time were recorded. An additional observation was made in one treated eye on day seven to assess the reversibility of the ocular effects. In result, a dulling of the normal lustre of the corneal surface was noted in one treated eye one hour after treatment with areas of diffuse corneal opacity at the 24, 48 and 72-hour observations. Iridial inflammation was noted in one treated eye one hour after treatment and at the 24 and 48-hour observations. No other adverse corneal or iridial effects were noted. Minimal to moderate conjunctival irritation was noted in all treated eyes one hour after treatment and in two treated eyes at the 24-hour observation. Moderate conjunctival irritation persisted in one treated eye at the 48-hour observation with minimal conjunctival irritation at the 72-hour observation. Treated eyes appeared normal 72 hours to 7 days after treatment. The mean scores for corneal opacity, iridial inflammation, conjunctival redness and conjunctival chemosis were below the value of 2 (max. 1.7). Acording to guideline, the test item did not produce positive effects in any test animal. In conclusion, the test item is regarded to be not corrosive or irritating to the eye. The test is regarded to be valid.

Justification for classification or non-classification

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

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on skin and eye irritation/corrosion, the test item is not classified to be irritating to skin or eye according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.