Registration Dossier

Administrative data

Description of key information

Skin irritation: non-corrosive, in vitro EpiDerm OECD TG 431, 2016
Skin irritation: Irritating, in vitro EpiSkin OECD TG 439, 2016
Eye irritation: non-irritating, in vivo OECD TG 405, 2000

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation / corrosion
Remarks:
in vitro
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Guideline study performed under GLP. All relevant validity criteria were met.
Qualifier:
according to
Guideline:
OECD Guideline 431 (In Vitro Skin Corrosion: Human Skin Model Test)
Deviations:
yes
Remarks:
Minor deviation in that the test tissues were stored refrigerated for 48 hours prior to testing; permitted under model SOP and guideline and which does not affect the reliability of the study
Qualifier:
according to
Guideline:
EU Method B.40 (In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test (TER))
Deviations:
yes
Remarks:
Minor deviation; see above.
GLP compliance:
yes (incl. certificate)
Remarks:
inspected June 2015; signature: September 2015
Test system:
human skin model
Source species:
human
Details on test system:
EpiDerm Skin Model (EPI-200-SCT, Lot no.: 21697). This model incorporates several features, which make it advantageous in the study of potential dermal corrosivity. The target cells are epithelial, derived from human skin, and formed into a stratified, cornified epithelium. Test items are applied to the culture surface, at the air interface, so that undiluted and/or end use dilutions can be tested directly. Pre-test checks for Direct MTT reduction and Colour Interference were completed.Preincubation:The assay medium was pre-warmed before use. 0.9 mL of this assay medium was pipetted into the appropriate wells of two pre-labelled 6-well plates for both the 3-Minute and 60-Minute exposure periods. EpiDerm™ tissues were transferred into the 6-well plates containing the assay medium. The 6-well plates containing the EpiDerm™ samples were pre-incubated (37 °C, 5% CO2) for approximately 1 hour before dosing.Application of test item and rinsing:After pre-incubation of the EpiDerm™ tissues, the medium was aspirated and replaced with 0.9 mL of fresh assay medium. Tissues were then dosed at regular intervals with test item/negative control and/or positive control respectively for the appropriate exposure times. Rinsing was achieved by filling and emptying each tissue under a constant soft stream of DPBS to gently remove any residual test item. The plate was incubated (37 °C, 5% CO2) for 3 hours. After the 3-Hour MTT incubation was complete, the inserts were blotted and transferred to labelled 24-well plates for MTT extraction.
Species:
other: EpiDerm Skin Model (EPI-200-SCT, Lot no.: 21697)
Strain:
not specified
Controls:
yes
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit): 50 μl- Concentration (if solution): undiluted
Duration of treatment / exposure:
Two tissues were used for a 3-minute exposure to the test substance and two for a 60-minute exposure.
Number of animals:
The test was performed on a total of 4 tissues per test substance (duplicate: 3-minutes and 6-minutes) together with a negative control and positive control in duplicate.
Details on study design:
TEST SITE- Area of exposure: 50 μl of the undiluted test substance was added on top of the skin tissues.REMOVAL OF TEST SUBSTANCE- Washing (if done): yes- Time after start of exposure: Two tissues were washed after 3 minutes and two tissues were washed after 60 minutes with Dulbeccos PBS (DPBS).SCORING SYSTEM: Skin corrosion is expressed as the remaining cell viability after exposure to the test substance at exposure times 3-minutes and 60-minutes, respectively. Where necessary, direct MTT reduction, colour interference and correction for background Isopropanol absorbance at OD562 (via measurement of triplicate blanks) was completed.
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
mean of two runs (n = 2); 3 minutes exposure to the test material
Value:
118.6
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: no indications of corrosion
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
mean of two runs (n = 2); 1 hour exposure to the test material
Value:
116.8
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: no indications of corrosion
Irritant / corrosive response data:
Table 1 shows the mean tissue viability obtained after 3-minute and 60-minute treatments with test substance compared to the negative control tissues. Skin corrosion is expressed as the remaining cell viability after exposure to the test substance.

Table 1. Mean absorption and tissue viability in the in vitro skin corrosion test with the test substance

Tissue

Exposure Period

Mean OD562 of individual tissues

Mean OD562 of duplicate tissues

Standard Deviation

Coefficient of Variation
(%)

Relative Mean Viability (%)

Negative Control

3 Minutes

1.865

1.843

0.03

1.7

100*

1.821

60 Minutes

1.891

1.919

0.04

2.1

1.947

Positive Control

3 Minutes

0.116

0.114

0.003

N/A

6.2

0.112

60 Minutes

0.098

0.112

0.02

N/A

5.8

0.125

Test Item

3 Minutes

2.271

2.186

0.1

5.5

118.6

2.101

60 Minutes

2.270

2.241

0.04

1.8

116.8

2.212

* = The mean % viability of the negative control tissue is set at 100%

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the test substance is not considered to be corrosive in the in vitro skin corrosion test using EpiDerm Skin Model.
Executive summary:

The study was performed to OECD TG 431 and EU Method B.40 BIS to assess the skin corrosion potential of the test substance in accordance with GLP using a human three dimensional epidermal model (EpiDerm (EPI-200)). Duplicate tissues were treated with the test item for exposure periods of 3 and 60 minutes. At the end of the exposure period the test item was rinsed from each tissue before each tissue was taken for MTT-loading. After MTT loading each tissue was placed in 2 mL Isopropanol for MTT extraction. At the end of the formazan extraction period each well was mixed thoroughly and triplicate 200 μL samples were transferred to the appropriate wells of a pre-labelled 96-well plate. The optical density (OD) was measured at 562 nm (OD562). The mean OD562 for the negative control treated tissues was 1.843 for the 3 Minute exposure period and 1.919 for the 60 Minute exposure period. The relative mean tissue viability obtained after the 3-minute and 1-hour treatments with the test substance compared to the negative control tissues was 118.6% and 116.8% respectively. The relative mean tissue viability for the positive control treated tissues was 5.8% relative to the negative control following the 60 Minute exposure period. The quality criteria required for acceptance of results in the test were satisfied. Under the conditions of this study, the test item was considered to be non-corrosive to the skin.

Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Guideline study performed under GLP. All relevant validity criteria were met.
Qualifier:
according to
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
inspected June 2015; signature: September 2015
Test system:
human skin model
Source species:
human
Details on test system:
EpiSkin RHE Model (Lot no.: 15-EKIN-042). The principle of the assay is based on the measurement of cytotoxicity in reconstructed human epidermal cultures following topical exposure to the test item by means of the colorimetric MTT reduction assay. Cell viability is measured by enzymatic reduction of the yellow MTT tetrazolium salt. to a blue formazan salt (within the mitochondria of viable cells) in the test item treated tissues relative to the negative controls. As a complimentary endpoint the concentration of the inflammatory mediator IL-1α in the culture medium retained following the 42-Hour post-exposure incubation period may also be determined for test items which are found to be borderline non-irritant based upon the MTT reduction endpoint. The EPISKINTM model is a three-dimensional reconstructed human epidermis model consisting of adult human-derived epidermal keratinocytes seeded on a dermal substitute consisting of a collagen type I matrix coated with type IV collagen. A highly differentiated and stratified epidermis model is obtained after a 13-Day culture period comprising of the main basal, supra basal, spinous and granular layers and a functional stratum corneum. Pre-test checks for Direct MTT reduction and Colour Interference were completed.Preincubation:Before removal from the transport plate each tissue was inspected for any air bubbles between the agarose gel and the insert. 2 mL of maintenance medium, warmed to approximately 37 °C, was pipetted into the first column of 3 wells of a pre-labelled 12-well plate. Each epidermis unit was transferred into the maintenance medium filled wells (3 units per plate). A different 12-well plate was used for the test item and each control item. The tissues were incubated at 37 °C, 5% CO2 in air overnight.Application of test item and rinsing: 2 mL of maintenance medium, warmed to approximately 37 °C, was pipetted into the second column of 3 wells of the 12-well plate. Triplicate tissues were treated with the test item for an exposure period of 15 minutes. The test item was applied topically to the corresponding tissues ensuring uniform covering. 10 μL (26.3 μL/cm2) of the test item was applied to the epidermis surface. Triplicate tissues treated with 10 μL of DPBS served as the negative controls and triplicate tissues treated with 10 μL of SDS 5% w/v served as the positive controls. At the end of the exposure period, each tissue was removed from the well using forceps and rinsed using a wash bottle containing DPBS with Ca++ and Mg++. Rinsing was achieved by filling and emptying each tissue insert for approximately 40 seconds using a constant soft stream of DPBS to gently remove any residual test item. The rinsed tissues were transferred to the second column of 3 wells containing 2 mL of maintenance medium in each well. The rinsed tissues were incubated at 37 °C, 5% CO2 in air for 42 hours.The tissues were subsequently placed into was placed onto a plate shaker for 15 minutes to homogenize the released mediators in the maintenance medium. 1.6 mL of the maintenance medium from beneath each tissue was transferred to pre-labelled micro tubes and stored in a freezer at -14 to -30 ºC for possible inflammatory mediator determination. Following 42 hour post exposure incubation the treated plates were then tested for MTT formazan extraction.
Species:
other: EPISKIN TM Small Model
Strain:
not specified
Controls:
other: negative and positive controls were used
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit): 10 µl- Concentration (if solution): undiluted
Duration of treatment / exposure:
Tissues were treated with the test material for 15 minutes and then washed with DPBS with Ca++ and Mg++ to remove residual test material. Subsequently the skin tissues were incubated for 42 hours at 37°C.
Details on study design:
TEST SITE- Area of exposure: 10 μl of the undiluted test substance was added topically into 12-well plates on top of the skin tissues.To ensure satisfactory contact with the positive control item the SDS solution was spread over the entire surface of the epidermis using a pipette tip (taking particular care to cover the center). After a 7-Minute contact time the SDS solution was re-spread with a pipette tip to maintain the distribution of the SDS for the remainder of the contact period (re-spreading is not required for the negative control or test item)REMOVAL OF TEST SUBSTANCE- Washing (if done): yes- Time after start of exposure: 15 minutesSCORING SYSTEM: Skin irritation potential of the test substance was classified according to remaining cell viability following exposure of the test substance.
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
mean of three runs (n = 3); 15 minutes exposure to the test material
Value:
28.9
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other:
Remarks:
Basis: mean. Time point: 15 minute exposure. Reversibility: no data. Remarks: n=3; SD = 12.2% ; Score in terms of percentage of negative control.

Table 1. Mean absorption and tissue viability in the in vitro skin irritation test with the test substance

Item

OD562 of tissues

Mean OD562 of triplicate tissues

± SD of OD562

Relative individual tissue viability (%)

Relative mean viability (%)

± SD of Relative mean viability (%)

Negative Control Item

0.687

0.643

0.041

106.8

100*

6.3

0.607

94.4

0.634

98.6

Positive Control Item

0.130

0.105

0.025

20.2

16.3

3.8

0.103

16.0

0.081

12.6

Test Item

0.276

0.186

0.078

42.9

28.9

12.2

0.143

22.2

0.138

21.5

OD = Optical Density

SD = Standard Deviation

* = The mean viability of the negative control tissues is set at 100%

 

The relative mean tissue viability for the positive control treated tissues was 16.3% relative to the negative control treated tissues and the standard deviation value of the viability was 3.8. The mean OD562 for the negative control treated tissues was 0.643 and the standard deviation value of the viability was 6.3. The standard deviation calculated from individual tissue viabilities of the three identically test item treated tissues was 12.2. All assay acceptance criteria were met.

 

Furthermore, within the Historic Control Data (HCD) (n=51): the mean OD of the positive control was 0.102; range 0.049 to 0.243 and the mean percentage viability was 12.2%; range 4.0% to 29.4%. In this same period the mean OD of the negative control was 0.851; range 0.629 – 1.245. The negative and positive control values obtained in this test fell within the historical range. It was therefore considered that comparison of the historical control data supports correct functioning of the test system.

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Under the conditions of this in vitro study, the test material is considered to be irritating to skin.
Executive summary:

The study was performed to OECD TG 439 and EU Method B.46 to assess the skin irritation potential of the test substance in accordance with GLP using a human three dimensional epidermal model (EPISKIN Small Model). Triplicate tissues were treated with the test item for an exposure period of 15 minutes. At the end of the exposure period each tissue was rinsed before incubating for 42 hours. At the end of the post-exposure incubation period each tissue was taken for MTT-loading. The maintenance medium from beneath each tissue was transferred to pre-labeled micro tubes and stored in a freezer for possible inflammatory mediator determination. After MTT-loading a total biopsy of each epidermis was made and placed into micro tubes containing acidified isopropanol for extraction of formazan crystals out of the MTT-loaded tissues. At the end of the formazan extraction period each tube was mixed thoroughly and duplicate 200 μL samples were transferred to the appropriate wells of a pre-labelled 96-well plate. The optical density was measured at 562 nm. Data are presented in the form of percentage viability (MTT reduction in the test item treated tissues relative to negative control tissues). The relative mean viability of the test item treated tissues was 28.9% after the 15-Minute exposure period and 42-Hours post-exposure incubation period. All assay acceptability criteria were met. Under the conditions of this study, the test substance is considered irritating to the skin and would be considered to meet the criteria under Regulation (EC) 1272/2008 for Skin Irritation Category 2: Irritant.

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

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2000
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Guideline study performed under GLP. The reliability score assigned 'reliable with restrictions' relates to applicant expert assessment on the study documentation and test item fields as summarised.
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
GLP compliance:
yes
Species:
rabbit
Strain:
other: SPF Albino ; Chbb:HM(SPF)
Details on test animals or tissues and environmental conditions:
TEST ANIMALS- Weight at study initiation: 1.9 - 2.0 kg- Housing: individual in PPO cages with perforated floor.- Diet (e.g. ad libitum): ad libitum Altromin 2123 (certificates of analysis retained)- Water (e.g. ad libitum): domestic drinking water; treated to prevent microbial growth (certificates of analysis retained)- Acclimation period: Housed pre-test for 7 days individually under same conditions as the main test.ENVIRONMENTAL CONDITIONS- Temperature (°C): 20 ± 3 °C- Humidity (%): 55 ± 15 %- Air changes (per hr): 10 per hour- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours lightIN-LIFE DATES: From: To: 04.04.2000 - 12.04.2000
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.1 mL- Concentration (if solution): neat (unchanged)
Duration of treatment / exposure:
24 hours treatment (rinsing performed at 24 hours with 20 ml 0.9% v/v Sodium Chloride solution post-reading and pre-corneal reading )
Observation period (in vivo):
4 days (observations were completed every day from day 1 to day 7 post treatment; terminated as all effects had reversed by day 7).
Number of animals or in vitro replicates:
4 (sex: female)
Details on study design:
REMOVAL OF TEST SUBSTANCE- Washing (if done): Yes.- Time after start of exposure: 24 hours.SCORING SYSTEM: Consistent to Draize scoring system.TOOL USED TO ASSESS SCORE: hand-slit lamp / fluorescein (with supplemental UV-light to detect corneal damage).
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
16
Remarks on result:
other: n = 4; maximum category score = 4; reading both before and after instillation of Fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: day 7
Score:
0
Max. score:
16
Remarks on result:
other: n = 4; maximum category score = 4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
8
Remarks on result:
other: n =4; maximum category score = 2
Irritation parameter:
iris score
Basis:
mean
Time point:
other: day 7
Score:
0
Max. score:
8
Remarks on result:
other: n =4 ; maximum category score = 2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1.3
Max. score:
12
Remarks on result:
other: n =4 ; maximum category score = 3; conjunctivae redness -> maximum score = 2.0 at 24 hours.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: day 7
Score:
0
Max. score:
12
Remarks on result:
other: n =4 ; maximum category score = 3
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
16
Remarks on result:
other: n =4 ; maximum category score = 4; chemosis -> maximum score = 2.0 at 24 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: day 7
Score:
0
Max. score:
16
Remarks on result:
other: n =4 ; maximum category score = 4; chemosis -> maximum score = 0
Irritant / corrosive response data:
Following scoring at 24, 48 and 72 h: No positive corneal scores. No positive iridal scores. Positive conjunctivae redness mean scores in 0/4 rabbits. Positive chemosis mean scores in 0/4 rabbits. All scores for all effect categories were less than or equal to 2.0 in all animals on all days (24 to 72hs; and up to 7 days). Discharge positive scores were also absent.

Individual scoring data was presented within the study report. No positive responses observed based on applicant recalculation of the results under the Regulation (EC) 1272/2008 criteria as amended.

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the test substance would not be considered as an eye irritant.
Executive summary:
The study was performed according to OECD TG 405 and EU Method B.5 acute eye irritation in vivo and in accordance with GLP. A volume of 0.1 ml of the test material was placed into the conjunctival sac of one eye of 4 animals sequentially using an initial sentinel organism. The other eye remained untreated and was used for control purposes. The eyes were examined and the changes were graded according to a numerical scale one hour, 24, 48 and 72 hours as well as 7 days after dosing. Well-defined signs of irritation were observed an the treated eyes. All effects were fully reversible within 7 days. The calculated mean values based on the results from the 24, 48 and 72 hour readings were calculated as: cornea: 0; iris lesion: 0; conjunctival redness: 1.33, 1.67, 1.33 and 1.00. Chemosis was 1.0 for all test organisms. 7 days after dosing all effects had fully reversed in all organisms. Under the conditions of this study the test substance has the potential to cause mild transient irritation based on applicant’s calculation of the mean scores following grading at 24, 48 and 72h and the individual scores, the test material is not considered to be irritating to the eye under Regulation (EC) 1272/2008 criteria.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

In vitro, OECD 439 2016 - The study was performed to OECD TG 439 and EU Method B.46 to assess the skin irritation potential of the test substance in accordance with GLP using a human three dimensional epidermal model (EPISKIN Small Model). Triplicate tissues were treated with the test item for an exposure period of 15 minutes. At the end of the exposure period each tissue was rinsed before incubating for 42 hours. At the end of the post-exposure incubation period each tissue was taken for MTT-loading. The maintenance medium from beneath each tissue was transferred to pre-labelled micro tubes and stored in a freezer for possible inflammatory mediator determination. After MTT-loading a total biopsy of each epidermis was made and placed into micro tubes containing acidified isopropanol for extraction of formazan crystals out of the MTT-loaded tissues. At the end of the formazan extraction period each tube was mixed thoroughly and duplicate 200 μL samples were transferred to the appropriate wells of a pre-labelled 96-well plate. The optical density was measured at 562 nm. Data are presented in the form of percentage viability (MTT reduction in the test item treated tissues relative to negative control tissues). The relative mean viability of the test item treated tissues was 28.9% after the 15-Minute exposure period and 42-Hours post-exposure incubation period. All assay acceptability criteria were met. Under the conditions of this study, the test substance is considered irritating to the skin and would be considered to meet the criteria under Regulation (EC) 1272/2008 for Skin Irritation Category 2: Irritant.

 

Skin corrosion:

In vitro, OECD 431 2015 - The study was performed to OECD TG 431 and EU Method B.40 BIS to assess the skin corrosion potential of the test substance in accordance with GLP using a human three dimensional epidermal model (EpiDerm (EPI-200)). Duplicate tissues were treated with the test item for exposure periods of 3 and 60 minutes. At the end of the exposure period the test item was rinsed from each tissue before each tissue was taken for MTT-loading. After MTT loading each tissue was placed in 2 mL Isopropanol for MTT extraction. At the end of the formazan extraction period each well was mixed thoroughly and triplicate 200 μL samples were transferred to the appropriate wells of a pre-labelled 96-well plate. The optical density (OD) was measured at 562 nm (OD562). The mean OD562 for the negative control treated tissues was 1.843 for the 3 Minute exposure period and 1.919 for the 60 Minute exposure period. The relative mean tissue viability obtained after the 3-minute and 1-hour treatments with the test substance compared to the negative control tissues was 118.6% and 116.8% respectively. The relative mean tissue viability for the positive control treated tissues was 5.8% relative to the negative control following the 60 Minute exposure period. The quality criteria required for acceptance of results in the test were satisfied. Under the conditions of this study, the test item was considered to be non-corrosive to the skin.

 

Eye irritation/corrosion:

In vivo, OECD TG 405 2000 - The study was performed according to OECD TG 405 and EU Method B.5 acute eye irritation in vivo and in accordance with GLP. A volume of 0.1 ml of the test material was placed into the conjunctival sac of one eye of 4 animals sequentially using an initial sentinel organism. The other eye remained untreated and was used for control purposes. The eyes were examined and the changes were graded according to a numerical scale one hour, 24, 48 and 72 hours as well as 7 days after dosing. Well-defined signs of irritation were observed an the treated eyes. All effects were fully reversible within 7 days. The calculated mean values based on the results from the 24, 48 and 72 hour readings were calculated as: cornea: 0; iris lesion: 0; conjunctival redness: 1.33, 1.67, 1.33 and 1.00. Chemosis was 1.0 for all test organisms. 7 days after dosing all effects had fully reversed in all organisms. Under the conditions of this study the test substance has the potential to cause mild transient irritation based on applicant’s calculation of the mean scores following grading at 24, 48 and 72h and the individual scores, the test material is not considered to be irritating to the eye under Regulation (EC) 1272/2008 criteria.


Justification for selection of skin irritation / corrosion endpoint:
two in vitro GLP compliant Klimisch 1 studies; selected study in accordance with sequential testing strategy of Regulation (EC) 440/2008 and its subsequent amendments.

Justification for selection of eye irritation endpoint:
one in vivo GLP compliant Klimisch 2 study

Justification for classification or non-classification

The substance meets the classification criteria under Regulation (EC) No 1272/2008 for skin irritation category 2, H315

 

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for eye irritation

 

For skin irritation, the weight of evidence indicates is the substance is predicted to be irritating to the skin sufficient for classification purposes. However, irritation is expected to be fully reversible.

 

For eye irritation, the weight of evidence indicates that the substance has the potential to cause mild transient irritating effects to the eye but which are insufficient for classification based on the applicants recalculation of the mean scoring and evaluation of the results in four organisms demonstrating that the EU criteria had not been met. Effects in vivo on corneal opacity and iritis are non-existent or very low; and the substance would be expected to only produce minor cytotoxic effects on the eye through fully reversible conjunctival redness and/or chemosis within a period of 7 days. The overall evidence is indicative of only transient and reversible effects on the eye not requiring classification.

 

References:

1. Guidance on Application of the CLP Criteria, ECHA, version 4.1 – June 2015