Registration Dossier

Administrative data

Description of key information

Classification of skin irritation was partly based on read across substance 'Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1-oxo(C12-C18(even numbered) and C18unsaturated)alkyl))amino]ethyl]esters, disodium salts'. The read across test substance containing 39.8% active ingredient was predicted to be irritant to human skin based on the three-dimensional EST 1000 human skin model (20 minutes exposure, followed by 42 hours incubation); the mean cell viability was 1.3% after a 20-minute exposure followed by 42 hours incubation, which was under 50% threshold level. However it was negative for corrosion in the same test model (3 minutes and 1 hour exposure); the mean cell viability was 101.0% and

78.0% after a 3-minute and 1-hour exposure, respectively, which were above threshold levels of 50 and 15%.

Formulations of the registered substance however, containing 10% or less active ingredient were previously tested to be non-irritant based on Draize method, therefore CLP category 2 classification is proposed with threshold for non classification at 10% or lower concentrations.
Classification of eye irritation was based on read across substance 'Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1-oxo(C12-C18(even numbered) and C18unsaturated)alkyl))amino]ethyl]esters, disodium salts' The read across test substance containing 39.9 % active ingredient was tested to be irritant to human eye based on the in vitro HET-CAM model; the test item treated eggs revealed an irritation index (IS) of 19, compared to19 for 0.1% NaOH. However it was not irritant in the in vivo eye irritation test. A 4% solution of the registered substance however was

previously tested to be mildly irritant based on the Draize method in rabbit eyes, however not classified.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The study was conducted according to GLP and valid methods and is considered relevant and reliable for classification. It is an in vitro study predicting skin irritation, which is considered adequate in combination with the in vitro corrosivity testing.
Qualifier:
according to guideline
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test system:
human skin model
Remarks:
EST1000
Source species:
human
Cell type:
non-transformed keratinocytes
Cell source:
other: not specified: Batch no. EST-120730-001; CellSytems® Biotechnology GmbH, 53842 Troisdorf, Germany
Justification for test system used:
Skin irritation by cytotoxic action of substances with direct human skin contact refers to the production of reversible damage to the skin following the application of a test item for up to 4 hours. This test method provides an in vitro procedure that, depending on information requirements, may allow determining the cytotoxic potency and skin irritancy of test items as a stand-alone replacement test within a testing strategy, in a weight of evidence approach.
The test method is based on reconstructed human epidermis models, which in their overall design (the use of human derived epidermis keratinocytes as cell source, representative tissue and cyto-architecture) closely mimic the biochemical and physiological properties of the upper parts of the human skin, i.e. the epidermis.
Vehicle:
unchanged (no vehicle)
Details on test system:
RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: The Skin model EST1000 was used.
- Tissue batch number(s): Batch no. EST-120730-001; CellSytems® Biotechnology GmbH, 53842 Troisdorf, Germany
- Production date: August 13, 2012
- Shipping date: Not provided.
- Delivery date: Not provided.
- Date of initiation of testing:
Start of the experimental phase: July 18, 2012
Termination of the experimental phase: August 16, 2012

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 21°C
The models were cultivated at 21°C for 20 minutes according to the instructions of the EST1000 supplier CellSystems®.
- Temperature of post-treatment incubation: not specified
Viability measurements were not performed immediately after the exposure to the test item, but after a post-treatment incubation period of the rinsed tissues in fresh medium of 42-hours.

REMOVAL OF TEST MATERIAL AND CONTROLS
- Number of washing steps: 1
At the end of the exposure period, the test item was carefully washed from the skin surface with Dulbecco's phosphate buffered saline (D-PBS)

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: MTT solution of 1 mg/mL
- Incubation time: 3 hours (37°C incubation temperature, 5% CO2, 95% humidity)
- Spectrophotometer: Yes, no further details given.
- Wavelength: 540 nm

FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
- Viability: The preferred assay for determining the magnitude of viability was the MTT. The optical density (OD) of the extracted (solubilised) dye from the tissue treated with the negative control (NC) should be at least 20-fold greater than the OD of the extraction solvent alone. The tissue treated with NC should exhibit stability in culture (provide similar viability measurements) for the duration of the test exposure period.
- Barrier function: Each batch of the epidermal model used meets defined production release criteria, set by the supplier, among which those for viability and for barrier function are the most relevant (MTT, 2 hours Triton X-100: target > 50%; result 58.5%). The barrier properties of the tissues were verified by the supplier.
- Morphology: No. of cornified layers and No. of vital cell layers were in line with the target of 5 and 4 respectively.
- Contamination: The skin model was free of contamination by bacteria, viruses, mycoplasma, or fungi.
- Reproducibility: Associated and appropriate measures of variability between tissue replicates are defined (e.g. if standard deviations should be ≤ 18%).

NUMBER OF REPLICATE TISSUES: 3

CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE
Not applicable

NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION:
1 ( at 20 min exposure + 42 h post-treatment incubation)
9 tests in total (Negative control, Test item and Positive control in triplicate at 1 timepoint)


PREDICTION MODEL / DECISION CRITERIA

- The test substance is considered to be irritant to skin with UN GHS category 2 if the tissue viability after exposure and post-treatment incubation was ≤ 50%
- The test substance is considered to have no category if the tissue viability after exposure and post-treatment incubation was > 50%.
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 75.3 µL Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1- oxo(C12-C18(even numbered) and C18unsaturated)alkyl))amino]ethyl]esters, disodium salts, were applied to the skin model with a surface of 0.6 cm2 to uniformly cover the skin surface. Usually 30 µL are used, however as the supplied test item contains only 39.8% active matter, a correction factor of 2.51 was used.

NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 75.3 µL
- Concentration (if solution): water for injection Batch no. 120378141, B. Braun Melsungen AG, 34212 Melsungen, Germany

POSITIVE CONTROL
- Amount(s) applied (volume or weight): 30 µL
- Concentration (if solution): 5% aqueous sodium dodecyl sulphate (SDS) Batch no. 15733; SERVA Electrophoresis GmbH, 69115 Heidelberg, Germany
Duration of treatment / exposure:
20 minutes
Duration of post-treatment incubation (if applicable):
42 h
Number of replicates:
3
Irritation / corrosion parameter:
% tissue viability
Remarks:
mean of 3 replicates; % versus negative control group
Run / experiment:
test group
Value:
1.3
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: Time point: 20 minutes, followed by 42h incubation.
Irritation / corrosion parameter:
% tissue viability
Remarks:
mean of 3 replicates; % versus negative control group
Run / experiment:
positive control group
Value:
1.3
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: Time point: 20 minutes, followed by 42h incubation.
Other effects / acceptance of results:
- OTHER EFFECTS:
- Direct-MTT reduction: No interactions of the test item with MTT were noted.

DEMONSTRATION OF TECHNICAL PROFICIENCY:
The viability of cells treated with the positive reference item, 5% SDS, was 1.3% of the negative controls and below the 50% cut-off value. Hence, 5% SDS is predicted to cause pronounced skin irritation.
All quality criteria required were fulfilled.
No interactions of the test item with MTT were noted.

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control (NC): For each assay using valid batches, tissues treated with the NC exhibit OD reflecting the quality of the tissue that followed all shipment and receipt steps and all the irritation protocol process. The OD values of controls should not be below historical established lower boundaries.
- Acceptance criteria met for positive control (PC): Tissues treated with the PC, i.e. 5% aqueous SDS, should reflect the sensitivity retained by tissues and their ability to respond to an irritant substance in the conditions of each individual assay (e.g. viability ≤ 50% for the validated method)
- Acceptance criteria met for variability between replicate measurements: Associated and appropriate measures of variability between tissue replicates are defined (e.g. if standard deviations should be ≤ 18%).

The cell viability was measured by determining the optical density (OD) at a wavelength of 540 nm. An exposure time of 20 minutes was employed.

The test item, Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1- oxo(C12-C18(even numbered) and C18unsaturated)alkyl))amino]ethyl]esters, disodium salts,was applied to the model skin surface. Water for injection was used as the negative control. 5% aqueous sodium dodecyl sulphate (SDS) was used as the positive reference item.

The mean viability of cells exposed to the test item was 1.3% of the negative controls and, hence, below the 50% cut-off value.The test item was considered to be cytotoxic and is predicted to be irritant to skin in accordance with UN GHS category 2.

The viability of cells treated with the positive reference item, 5% SDS,was 1.3% of the negative controls and below the 50% cut-off value. Hence, 5% SDS is predicted to cause pronounced skin irritation.

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Under the present test conditions Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1- oxo(C12-C18(even numbered) and C18unsaturated)alkyl))amino]ethyl]esters, disodium salts, tested at an exposure time of 20 minutes, was cytotoxic and, hence, irritant to skin in an experiment employing an artificial three-dimensional model of human skin.

Executive summary:

The purpose of this study was to determine cytotoxic properties to skin cells, which might lead to irritation by Butandioic acid, 2(or 3)-sulfo, 4 - [2 - [(1 -oxo(C12 -C18(even numbered) and C18 unsaturated)alkyl)amino]ethyl], esters, disodium salts to human skin, in an experiment with an artificial three-dimensional model of human skin. The EST1000 model was employed. The test item containing 39.8% active ingredient was applied. The cell viability was measured by determining the optical density (OD) at a wavelength of 540 nm. An exposure time of 20 minutes was employed, followed by refreshment of the medium and further 42 hours incubation. Water for injection was used as the negative control. 5% aqueous sodium dodecyl sulphate (SDS) was used as the positive reference item. The mean viability of cells exposed to the test item was 1.3% of the negative controls and, hence, below the 50% cut-off value. The test item was considered to be cytotoxic and is predicted to be irritant to skin in accordance with UN GHS category 2.

The viability of cells treated with the positive reference item, 5% SDS, was 1.3% of the negative controls and below the 50% cut-off value. Hence, 5% SDS is predicted to cause pronounced skin irritation.

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

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
according to guideline
Guideline:
other: ICCVAM-Recommended Test Method Protocol: Hen’s Egg Test – Chorioallantoic Membrane (HET-CAM) Test Method, published 2010.
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
other: fertile chicken eggs
Strain:
other: White legghorn
Vehicle:
physiological saline
Controls:
yes, concurrent positive control
yes, concurrent negative control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 300 µL/egg (used undiluted)
Duration of treatment / exposure:
20 seconds
Observation period (in vivo):
5 minutes
Irritation parameter:
other: Irritation score
Remarks:
mean
Run / experiment:
test item
Value:
18.6
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: maximum score 21.0
Irritation parameter:
other: irriatation score
Remarks:
mean
Run / experiment:
0.1% NaOH positive control
Value:
19.4
Remarks on result:
other: maximum score 21.0
Irritation parameter:
other: irritation score
Remarks:
mean
Run / experiment:
1% SDS positive control
Value:
10
Remarks on result:
other: maximum score 21.0
Irritation parameter:
other: irritation score
Remarks:
mean
Run / experiment:
negative control
Value:
0
Remarks on result:
other: maximum score 21.0
Other effects / acceptance of results:
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: The HET-CAM assay is considered acceptable if the negative controls each induce a response that falls within the classification of nonirritating.
- Acceptance criteria met for positive control: The HET-CAM assay is considered acceptable if the positive controls each induce a response that falls within the classification of severely irritating, respectively.
- Range of historical values: Historical control studies demonstrate that using 1% SDS and 0.1 N NaOH as positive controls results in IS values of approximately 10 and 18, respectively.

The eggs treated with Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1- oxo(C12-C18(even numbered) and C18unsaturated)­alkyl))amino]­ethyl]­esters, disodium salts revealed a pronounced effect with an irritation index (IS) of 18.6. The test item was considered to be strong irritant.

The positive control items 0.1% NaOH or 1% SDS caused the expected effect with irritation indices (IS) of 19.4 or 10.0, respectively and, hence, were well within the historical data-range. No effects were observed in the negative control 0.9% NaCl solution. Hence, the HET-CAM assay is considered to be valid.

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Under the present test conditions, Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1- oxo(C12-C18(even numbered) and C18unsaturated)alkyl))amino]ethyl]esters, disodium salts was strong irritant to eyes in an experiment with the chorioallantoic membrane of hens' eggs (HET-CAM).
Executive summary:

The purpose of this study was to determine the eye irritancy potential of Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1- oxo(C12-C18(even numbered) and C18unsaturated)alkyl))amino]ethyl]esters, disodium salts by means of the chorioallantoic membrane of hens' eggs (HET-CAM). Eye irritation caused by external contact with chemical substances is characterized by corneal damage and/or conjunctival injury and/or iris defects. The CAM of fertile eggs incubated for 9 days is a vital vascular membrane with a blood vessel complex.

Three eggs each were treated with 300 µL Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1- oxo(C12-C18(even numbered) and C18unsaturated)alkyl))amino]ethyl]esters, disodium salts/egg and with the control items. 0.9% NaCl solution was used as the negative control item. 0.1 N Sodium hydroxide (NaOH) and 1% aqueous sodium dodecyl sulphate (SDS) were used as the positive control items. The administration volume for the control items was 300 µL per egg.

After administration of the test item blood vessels including the capillary system and the albumen were examined and scored for irritant effects (haemorrhage, coagulation and lysis) during 5 minutes.

The eggs treated with Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1- oxo(C12-C18(even numbered) and C18unsaturated)­alkyl))amino]­ethyl]­esters, disodium salts revealed a pronounced effect with an irritation index (IS) of 18.6. The test item was considered to be strong irritant.

The positive control items 0.1or 1% SDS caused the expected effect with irritation indices (IS) of 19.4 or 10.0, respectively and, hence, were well within the historical data-range. No effects were observed in the negative control 0.9% NaCl solution. Hence, the HET-CAM assay is considered to be valid.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

A. Weight-of-evidence was available for classification of skin irritation at concentrations of 39.8% active ingredient, based on read across with data of 'Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1-oxododecyl)amino]ethyl]ester, disodium salt'. Justification for read across within the category of N-containing sulphosuccinates (N2 subcategory) is documented in a separate document attached in Section 13.

- In a first study, the corrosive properties were studied in an experiment with a three-dimensional EST-1000 human skin model (Flügge, 2013a). The test item (containing 39.8% active ingredient) was applied for exposure times of 3 minutes or 1 hour. The mean viability of cells exposed to the test item was 101.0% after a 3-minute exposure period and 78.0% after a 1-hour exposure. These values were well above the cut-off percentage cell viability values distinguishing corrosive from non-corrosive test items of <50% or <15% for a 3-minute or 1-hour treatment. Therefore, the test item was non-corrosive in this human skin model and is predicted to be non-corrosive to human skin.

- In a second study, the irritant properties to skin cells were also studied in an experiment with a three-dimensional EST-1000 human skin model (Flügge, 2013b). The test item (containing 39.8% active ingredient) was applied for an exposure time of 20 minutes, followed by refreshment of the medium and further 42 hours incubation. The mean viability of cells exposed to the test item was 1.3% of the negative controls and, hence, below the 50% cut-off value. The test item was considered to be cytotoxic and is predicted to be irritant to skin in accordance with UN GHS category 2. The viability of cells treated with the positive reference item, 5% SDS, was 1.3% of the negative controls and below the 50% cut-off value. Hence, 5% SDS is predicted to cause pronounced skin irritation.

- According to ECHA progress report 2010 (p. 32), it is accepted that in vitro methods for skin irritation represent a full replacement of the in vivo method in a tiered testing strategy and in conjunction with in vitro skin corrosivity tests, if necessary. A positive result in the human skin model for irritation does not need to be confirmed by additional testing and shall lead to classification.

 

B. Three supporting studies were available for the registered substance with formulations of 10% and lower.

- In a first acute dermal irritation/corrosion test on 6 albino rabbits (Oetjen and Lindena, 1990a) the potential toxicity of a test item containing 10% active ingredient was assessed. The skin was exposed to 0.5 mL for 4 h. Animals were examined for signs of erythema and oedema at 30-60 min, 24, 48 and 72 h after the end of the exposure period, showing absence of any signs up to 72 hours.

- In a second dermal irritation study in humans (Kligman, 1977) a 10-day occlusive patch test method was used as follows: 1, 5 and 10% concentrations were applied daily to the forearms of 10 young-adult female college students. 1% produced no visible reaction in any of the subjects. By the sixth day, some of the volunteers treated with 5% began to exhibit mild erythema which gradually worsened thereafter. The results with 10% were indistinguishable from the 5% concentration. 5 and 10% are mildly irritating when applied under continuous occlusion. The latter mode of exposure is, of course, greatly exaggerated in relation to normal use.

- In a third skin irritation study according to the modified methylene blue method in humans to study the desiccation on skin (Biefeldt and Schrader, 1991) 10mL of a 2% concentration was filled in a glass container and brought in contact with the skin of the forearms. After 15 seconds the product was discarded and the forearms were washed with 500 mL lukewarm water and blotted with paper towels followed by a 60 minutes rest period. Methylene blue solution was applied on the treated areas and further measured in the Zeiss spectrophotometer at 660nm against air. The test item was shown to be a mild detergent and falls in the category of low roughening.

 

Eye irritation

A. Weight-of-evidence was available for classification of eye irritation at concentrations (39.8% active ingredient), based on read across data of 'Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1-oxododecyl)amino]ethyl]ester, disodium salt'. Justification for read across within the category of N-containing sulphosuccinates (N2 subcategory) is documented in a separate document attached in Section 13.

- In a first in vitro study the eye irritancy potential of test item containing 39.8% active ingredient was tested by means of the chorioallantoic membrane of hens' eggs (HET-CAM) method (Haferkorn, 2012). Three eggs each were treated with 300 µL/egg. After administration of the test item, blood vessels including the capillary system and the albumen were examined and scored for irritant effects (haemorrhage, coagulation and lysis) during 5 minutes. The test item treated eggs revealed a pronounced effect with an irritation index (IS) of 19, compared to IS of 19 or 10 for 0.1% NaOH and 1% SDS positive controls and no effects in the negative control0.9% NaCl solution. The test item was predicted to be irritating.

- In a second in vitro study severe eye irritancy potential and corrosivity potential of the test item containing 39.8% active ingredient was tested by means of the BCOP test method (Leuschner, 2013).Three corneas were used for each treatment group (test item, negative and positive controls). The test item was used as a 3.98-fold dilution in 0.9% NaCl-solution in order to obtain a 10% w/v dilution of active ingredient, which complies with the guideline requirements for surfactants. 0.9% NaCl solution was used as the negative control and 1% NaOH solution as the positive control item. An IVIS score of 21.90 was calculated, hence the test item was not classified as a severe irritant and not corrosive, based on the results of this test. The corneas treated with the positive control item 1% NaOH solution revealed an IVIS score of 87.43 was well above the cut-off value of 55.1 and, hence, the acceptance criteria for the test were fulfilled. The test item, containing 39.8% active ingredient was consequently not classified as a severe irritant and is not corrosive.

- According to Column 2, the criteria for classification are met as irritating to eyes, based on weight of evidence, and further in vivo testing was therefore not needed.

 

B. Further in vivo studies were available for the read-across and registered substance with lower % formulations:

- In an in vivo study, read-across substance 'Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1-oxododecyl)amino]ethyl]ester, disodium salt' was tested according to the Draize mehod in rabbits (Baker Research Laboratories limited, 1962b). The test solutions were diluted with distilled water so that the content of active matter was reduced to 20% in each case. 0.1mL of the test solution (20% act. ingr.) was instilled into the conjunctival sac of one eye of each rabbit, the other eye serving as a control (3 rabbits were used). Readings were made visually and with the aid of an ophthalmoscope at 1, 2, 4, 6, 24, 48, 72 hours and 4 and 7 days after instillation and evaluated according to the Draize scoring method. Mild irritation was observed which was reversible within 3 days, which was below threshold of classification.

- Finally an in vivo study was also available with registered substance according to OECD Guideline 405 where 0.1 mL of test item containing 39% act.ingr. was instilled as a 10 % (v/v) aqueous solution into the conjunctival sac of the left eye of six White New Zealand rabbits (Oetjen and Lindena, 1990b). The eyes were not rinsed after substance application. Animals then were observed for 72 hours. At 1 h p.a. all animals showed slight redness and chemosis of the conjunctivae. At 24 hours p.a. slight conjunctival redness was still persistent in 5/6 animals and reversible in 1/6 animals. Chemosis persisted 24 hours p.a. only in 1/6 animals and was reversible in the other 5 animals. From 48 - 72 h p.a. no test article-dependent findings were observed. Active ingredient according to producers information: minimum 39 %.; taking this value into account, active ingredient of the test solution was 3.9 % in minimum.

- Based on these two in vivo studies and the structural similarity between registered and read-across substance, a concentration limit of 20% for non-classification can be set for the registered substance.

 

Conclusion:

- A subgroup CLP category 2 classification was decided for skin irritation, with concentration limit of 10% for non-classification of registered substance.

- A subgroup CLP category 2 classification was decided for eye irritation, with concentration limit of 20% for non-classification of registered substance.

- More information on the subgroup classification is provided in the read-across justification, separately attached in Section 13.

 

Justification for selection of skin irritation / corrosion endpoint: Although the in vitro study for irritation was selected, the corrosion study was equally valuable in a weight-of-evidence approach. 

Justification for selection of eye irritation endpoint: Although the in vitro study for irritation was selected, the other studies were equally valuable in a weight-of-evidence approach. 

Effects on skin irritation/corrosion: irritating 

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

The registered substance is classified for skin irritation according to CLP regulation (No. 1272/2008 of 16 December 2008), as Category 2, with signal word 'warning' and hazard statement: H315 - Causes skin irritation. However, a concentration limit of 10% for non-classification can be applied. For the eye, the test substance is classified as irritating to eyes according to CLP regulation as Category 2, with signal word 'warning' and hazard statement: H319 -Causes serious eye irritation. However, a concentration limit of 20% for non-classification can be applied.