Registration Dossier

Administrative data

Description of key information

Skin Corrosion/Irritation: Not classified; OECD 404; Sanders (2011)

Eye Irritation: Not classified; OECD 405, Sanders (2011)

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:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 23 June 2011 and 08 July 2011.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevant results.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147, amended 10 December 2002
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Health and Welfare, 1992
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Three New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories UK Ltd., Leicestershire, UK.
- Age at study initiation: Twelve to twenty weeks old.
- Weight at study initiation: 2.40 to 2.69 kg
- Housing: The animals were individually housed in suspended cages.
- Diet (e.g. ad libitum): Free access to food (2930 Teklad Global diet) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout the study.
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): set to achieve limits of 17 to 23°C
- Humidity (%): set to achieve limits of 30 to 70%
- Air changes (per hr): At least fifteen changes per hour.
- Photoperiod (hrs dark / hrs light): lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped free of fur
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
For the purpose of the study, the test item was ground to a powder before use.
The absorption of the test item was not determined.

At each test site a quantity of 0.5 g of the test item, moistened sufficiently with 0.5 ml of distilled water, was introduced.
Duration of treatment / exposure:
3 minutes (initial animal), 1 hour (initial animal) and 4 hours (all animals).
Observation period:
72 hours plus an additional observation was made at one treated skin site on Day 7.
Number of animals:
3
Details on study design:
MEASUREMENT OF PH:
The pH of the test item was determined prior to commencement of the study and found to be as follows:
10% w/w aqueous preparation of the test item: pH 4.5 (immediately and after 10 minutes).

PROCEDURE:
On the day before the test each rabbit was clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.

One rabbit was initially treated. Three suitable sites were selected on the back of the rabbit. At each test site a quantity of 0.5 g of the test item, moistened sufficiently with 0.5 ml of distilled water, was introduced sequentially under a 2.5 cm x 2.5 cm cotton gauze patch. Each patch was secured in position with a strip of surgical adhesive tape. To prevent the animal interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset for the duration of the exposure period.

One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application. Any residual test item was removed by gentle swabbing with cotton wool soaked in distilled water.

After consideration of the skin reactions produced in the first animal, an additional two animals were treated sequentially with 0.5 g of test item, moistened sufficiently with 0.5 ml of distilled water. One patch was applied to the back of each rabbit and was allowed to remain in contact with the skin for a period of four hours.

SCORING SYSTEM:
Immediately following removal of the patches and approximately 1, 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the Draize scale (see evaluation of skin reactions below).

Any other skin reactions and clinical signs of toxicity, if present, were also recorded.

An additional observation was made at one treated skin site on Day 7 to assess the reversibility of skin reactions.

Individual bodyweights were recorded on Day 0 (the day of dosing) and at the end of the observation period.










Irritation parameter:
erythema score
Basis:
mean
Remarks:
(Animal 1 - 70541)
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Result of 4 hour exposure
Irritation parameter:
edema score
Basis:
mean
Remarks:
(Animal 1 - 70541)
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Result of 4 hour exposure
Irritation parameter:
erythema score
Basis:
mean
Remarks:
(Animal 2 - 70668)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: Result of 4 hour exposure
Irritation parameter:
edema score
Basis:
mean
Remarks:
(Animal 2 - 70668)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: Result of 4 hour exposure
Irritation parameter:
erythema score
Basis:
mean
Remarks:
(Animal 3 - 70669)
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Result of 4 hour exposure
Irritation parameter:
edema score
Basis:
mean
Remarks:
(Animal 3 - 70669)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Result of 4 hour exposure
Irritant / corrosive response data:
Skin Reactions:

3-Minute Exposure Period:
The individual scores for erythema/eschar and oedema are given in Table 1.
No evidence of skin irritation was noted during the study.

1-Hour Exposure Period:
The individual scores for erythema/eschar and oedema are given in Table 1.
No evidence of skin irritation was noted during the study.

4-Hour Exposure Period:
The individual scores for erythema/eschar and oedema are given in Table 2.

Well-defined erythema and very slight oedema were noted at one treated skin site with very slight erythema and very slight oedema at one other treated skin site immediately and one hour after patch removal. Very slight erythema, with or without very slight oedema, was noted at these two treated skin sites at the 24-Hour observation. Very slight erythema and very slight oedema were noted at one of these treated skin sites at the 48-Hour observation with very slight erythema noted at the 72-Hour observation.

One treated skin site appeared normal at the 48-Hour observation and one other treated skin site appeared normal at the 7-Day observation.

No evidence of skin irritation was noted at one treated skin site during the study.

The individual mean scores for erythema and oedema required for classification according to the Globally Harmonised System of Classification and Labelling of Chemicals were as follows:
Animal 1 (70541):
Mean score for erythema/eschar formation: 1.0
Mean score for oedema formation: 0.7

Animal 2 (70668):
Mean score for erythema/eschar formation: 0.0
Mean score for oedema formation: 0.0

Animal 3 (70669):
Mean score for erythema/eschar formation: 0.3
Mean score for oedema formation: 0.0












Other effects:
Bodyweight:
Individual bodyweights and bodyweight changes are given in Table 3.
All animals showed expected gain in bodyweight during the study.

Table 1: Individual Skin Reactions Following 3 -Minute and 1 -Hour Exposures:

Skin Reaction

Observation Time (following patch removal)

Individual Scores – Rabbit Number and Sex

70541 Male

3-Minute Exposure

1-Hour Exposure

Erythema/Eschar Formation

Immediately

0

0

1 Hour

0

0

24 Hours

0

0

48 Hours

0

0

72 Hours

0

0

7 Days

0

0

Oedema Formation

Immediately

0

0

1 Hour

0

0

24 Hours

0

0

48 Hours

0

0

72 Hours

0

0

7 Days

0

0

Table 2: Individual Skin Reactions Following 4 -Hour Exposure

Skin Reaction

Observation Time (following patch removal)

Individual Scores – Rabbit Number and Sex

Total

70541 Male

70668 Male

70669 Male

Erythema/Eschar Formation

Immediately

2

0

1

(3)

1 Hour

2

0

1

(3)

24 Hours

1

0

1

2

48 Hours

1

0

0

(1)

72 Hours

1

0

0

1

7 Days

0

-

-

(0)

Oedema Formation

Immediately

1

0

1

(2)

1 Hour

1

0

1

(2)

24 Hours

1

0

0

1

48 Hours

1

0

0

(1)

72 Hours

0

0

0

0

7 Days

0

-

-

(0)

Sum of 24 and 72-Hour Readings (S): 4

Primary Irritation Index (S/6): 4/6 = 0.7

Classification: mild irritant

( ) = Total values not used for calculation of primary irritation index.

- = Not applicable.

Table 3: Individual Bodyweights and Bodyweight Changes

Rabbit Number and Sex

Individual Bodyweight (kg)

Bodyweight Change (kg)

70541 Male

Day 0

Day 7

0.14

2.54

2.68

70668 Male

Day 0

Day 3

0.08

2.40

2.48

70669 Male

Day 0

Day 3

0.04

2.69

2.73

 

Interpretation of results:
GHS criteria not met
Conclusions:
The test item produced a maximum individual mean score of 1.0 and therefore did not meet the criteria for classification according to the Globally Harmonised System of Classification and Labelling of Chemicals.
Executive summary:

The study was performed to assess the irritancy potential of the test item to the skin of the New Zealand White rabbit. The method was designed to be compatible with the following:

- OECD Guidelines for the Testing of Chemicals No. 404 “Acute Dermal Irritation/Corrosion” (adopted 24 April 2002)

- Method B4 Acute Toxicity (Skin Irritation) of Commission Regulation (EC) No. 440/2008

- United States Environmental Protection Agency Health Effects Test Guidelines OPPTS 870.2500 Acute Dermal Irritation August 1998

- Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147, amended 10 December 2002

- Japanese Ministry of Health and Welfare, 1992

3-minute and 1-hour semi-occluded applications of the test item to the intact skin of one rabbit produced no evidence of skin irritation. A single 4-hour, semi-occluded application of the test item to the intact skin of three rabbits produced very slight to well-defined erythema and very slight oedema. No evidence of skin irritation was noted at one treated skin site.

The test item produced a maximum individual mean score of 1.0 and therefore did not meet the criteria for classification according to the Globally Harmonised System of Classification and Labelling of Chemicals.

Endpoint:
skin corrosion: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
In accordance with REACH Regulation (EC) 1907/2006 as amended: Annex VII, section 8.1.1: the skin corrosion: in vitro / ex vivo study does not need to be conducted based on existing data sufficient for classification and labelling being already available. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7a: Endpoint Specific Guidance, R.7.2.2, October 2015) the study does not need to be conducted.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 11 July 2011 and 21 July 2011.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevant results.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147, amended 10 December 2002
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Health and Welfare, 1992
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Three New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories UK Ltd., Leicestershire, UK.
- Age at study initiation: twelve to twenty weeks old
- Weight at study initiation: At the start of the study the animals weighed 2.46 to 2.86 kg
- Housing: The animals were individually housed in suspended cages.
- Diet (e.g. ad libitum): Free access to food (2930 Teklad Global Rabbit diet) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout the study.
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Set to achieve limits of 17 to 23°C
- Humidity (%): Set to achieve limits of 30 to 70%
Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study.
- Air changes (per hr): At least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): Lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
For the purpose of the study the test item was ground before use.
The absorption of the test item was not determined.

A volume of 0.1 ml of the test item, which was found to weigh approximately 97 mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye.
Duration of treatment / exposure:
SIngle application.
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
MEASUREMENT OF PH:
The pH of the test item was determined prior to commencement of the study and found to be as follows:
10% w/w aqueous preparation of the test item: pH 4.5 (immediately)
: pH 4.5 (after 10 minutes)

PROCEDURE:
Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Only animals free of ocular damage were used.

Initially, a single rabbit was treated. A volume of 0.1 ml of the test item, which was found to weigh approximately 97 mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test item, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test item, an assessment of the initial pain reaction was made according to the six point scale shown in Appendix 1 (see attached background material).

After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.


SCORING SYSTEM:
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical Draize Scale for Scoring Ocular Irritation (see Appendix 2 - attached background material).

Any other ocular effects were also noted.

TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Other:
Any clinical signs of toxicity, if present, were also recorded.

Individual bodyweights were recorded on Day 0 (the day of dosing) and at the end of the observation period.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
(Animal 1 - 70681)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
(Animal 2 - 70736)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
(Animal 3 - 70737)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
(Animal 1 - 70681)
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
mean
Remarks:
(Animal 2 - 70736)
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
mean
Remarks:
(Animal 3 - 70737)
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
(Animal 1 - 70681)
Time point:
24/48/72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
(Animal 2 - 70736)
Time point:
24/48/72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
(Animal 3 - 70737)
Time point:
24/48/72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(Animal 1 - 70681)
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(Animal 2 - 70736)
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
(Animal 3 - 70737)
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
Ocular Reactions:
Individual and group mean scores for ocular irritation are given in Table 1 and Table 2.

No corneal or iridial effects were noted during the study.

Moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24 and 48-Hour observations.

All treated eyes appeared normal at the 72-Hour observation.
Other effects:
Individual bodyweights and bodyweight changes are given in Table 3.
All animals showed expected gain in bodyweight during the study.

Table 1              Individual Scores and Individual Total Scoresfor Ocular Irritation

Rabbit Number and Sex

70681 Male

70736 Male

70737 Male

IPR= 2

IPR = 2

IPR = 2

Time After Treatment

1
Hour

24
Hours

48
Hours

72
Hours

1
Hour

24
Hours

48
Hours

72
Hours

1
Hour

24
Hours

48
Hours

72
Hours

CORNEA

 

 

 

 

 

 

 

 

 

 

 

 

E = Degree of Opacity

0

0

0

0

0

0

0

0

0

0

0

0

F = Area of Cornea Involved

0

0

0

0

0

0

0

0

0

0

0

0

Score (E x F) x 5

0

0

0

0

0

0

0

0

0

0

0

0

IRIS

 

 

 

 

 

 

 

 

 

 

 

 

D

0

0

0

0

0

0

0

0

0

0

0

0

Score (D x 5)

0

0

0

0

0

0

0

0

0

0

0

0

CONJUNCTIVAE

 

 

 

 

 

 

 

 

 

 

 

 

A = Redness

2

1

1

0

2

1

1

0

2

1

1

0

B = Chemosis

2

1

0

0

2

1

0

0

2

1

0

0

C = Discharge

1

0

0

0

1

0

0

0

1

0

0

0

Score (A + B + C) x 2

10

4

2

0

10

4

2

0

10

4

2

0

Total Score

10

4

2

0

10

4

2

0

10

4

2

0

 

IPR=  Initial pain reaction

Table 2              Individual Total Scores and Group Mean Scores for Ocular Irritation

Rabbit Number

and Sex

Individual Total Scores At:

1 Hour

24 Hours

48 Hours

72 Hours

70681 Male

10

4

2

0

70736 Male

10

4

2

0

70737 Male

10

4

2

0

Group Total

30

12

6

0

Group Mean Score

10.0

4.0

2.0

0.0

Table 3              Individual Bodyweights and Bodyweight Changes

Rabbit Number
and Sex

Individual Bodyweight (kg)

Bodyweight Change (kg)

Day 0

Day 3

70681 Male

2.82

2.93

0.11

70736 Male

2.46

2.56

0.10

70737 Male

2.86

2.91

0.05

Interpretation of results:
GHS criteria not met
Conclusions:
A single application of the test item to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. All treated eyes appeared normal at the 72-Hour observation.
The test item does not meet the criteria for classification according to the Classification, Labelling and Packaging Regulation or the Globally Harmonised Classification System.
Executive summary:

The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit. The method was designed tobe compatible with thefollowing:

- OECD Guidelines for the Testing of Chemicals No. 405 “Acute Eye Irritation/Corrosion” (adopted 24 April 2002)

- Method B5 Acute Toxicity (Eye Irritation) of CommissionRegulation (EC) No. 440/2008

- United States Environmental Protection Agency Health Effects Tesat Guidelines OPPTS 870.2400 Acute Eye Irritation August 1998

- Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147, amended 10 December 2002

- Japanese Ministry of Health and Welfare, 1992

A single application of the test item to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. All treated eyes appeared normal at the 72‑Hour observation.

The test item does not meet the criteria for classification according to the Classification, Labelling and Packaging Regulation (CLP) or the Globally Harmonised Classification System.

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
In accordance with REACH Regulation (EC) 1907/2006 as amended: Annex VII, section 8.2.1: the eye irritation: in vitro / ex vivo study does not need to be conducted based on existing data sufficient for classification and labelling being already available. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7a: Endpoint Specific Guidance, R.7.2.2, October 2015) the study does not need to be conducted.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No in vitro studies were submitted for skin irritation/corrosion or eye irritation. In accordance with REACH Regulation (EC) 1907/2006 as amended: Annex VII, section 8.1 and 8.2, in vitro / ex vivo studies for skin corrosion/irritation and eye irritation do not need to be conducted based on existing data sufficient for classification and labelling being already available. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7a: Endpoint Specific Guidance, R.7.2.2, October 2015) the study does not need to be conducted.

Skin Irritation/Corrosion:

The study was performed to assess the irritancy potential of the test item to the skin of the New Zealand White rabbit. The method was designed to be compatible with the following:

- OECD Guidelines for the Testing of Chemicals No. 404 “Acute Dermal Irritation/Corrosion” (adopted 24 April 2002)

- Method B4 Acute Toxicity (Skin Irritation) of Commission Regulation (EC) No. 440/2008

- United States Environmental Protection Agency Health Effects Test Guidelines OPPTS 870.2500 Acute Dermal Irritation August 1998

- Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147, amended 10 December 2002

- Japanese Ministry of Health and Welfare, 1992

3-minute and 1-hour semi-occluded applications of the test item to the intact skin of one rabbit produced no evidence of skin irritation. A single 4-hour, semi-occluded application of the test item to the intact skin of three rabbits produced very slight to well-defined erythema and very slight oedema. No evidence of skin irritation was noted at one treated skin site.

The test item produced a maximum individual mean score of 1.0 and therefore did not meet the criteria for classification according to the Globally Harmonised System of Classification and Labelling of Chemicals.

Eye Irritation:

The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit. The method was designed tobe compatible with thefollowing:

- OECD Guidelines for the Testing of Chemicals No. 405 “Acute Eye Irritation/Corrosion” (adopted 24 April 2002)

- Method B5 Acute Toxicity (Eye Irritation) of CommissionRegulation (EC) No. 440/2008

- United States Environmental Protection Agency Health Effects Tesat Guidelines OPPTS 870.2400 Acute Eye Irritation August 1998

- Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Testing Guidelines for Toxicology Studies, 12 NohSan No. 8147, amended 10 December 2002

- Japanese Ministry of Health and Welfare, 1992

A single application of the test item to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. All treated eyes appeared normal at the 72‑Hour observation.

The test item does not meet the criteria for classification according to the Classification, Labelling and Packaging Regulation (CLP) or the Globally Harmonised Classification System.

Justification for classification or non-classification

The substance does not meet the criteria for skin corrosion/irritation or eye irritation in accordance with Regulation (EC) 1272/2008 (CLP).