Registration Dossier

Administrative data

Description of key information

skin irritation: not irritating (OECD 439; GLP)

eye irritation: not irritating (OECD 437; GLP)

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:
key study
Study period:
2018-04-25 to 2018-04-27
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Version / remarks:
2015-07-28
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: MatTek Corporation Protocol for: In Vitro EpiDermTM Skin Irritation Test (EPI-200-SIT) For use with MatTek Corporation’s Reconstructed Human Epidermal Model EpiDerm (EPI-200-SIT)
Version / remarks:
2014-11-07
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2015-06-05
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: ambient, tightly closed, store away from incompatible materials (e.g. strong oxidising agents)
Test system:
human skin model
Source species:
human
Cell type:
other: normal, human epidermal keratinocytes
Cell source:
other: humans
Source strain:
other: not applicable
Details on animal used as source of test system:
not applicable
Justification for test system used:
This test uses the EpiDerm™ reconstructed human epidermis model (MatTek) which consists of normal human-derived epidermal keratinocytes (NHEK) and therefore represents in vitro the target organ of the species of interest and closely resembles 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: EpiDermTM (EPI-200-SIT; MatTek)
- Tissue lot number: 25899

TEST FOR MTT INTERFERENCE
- to check the non-specific MTT-reducing capability of the test item 30 µl of the test item were mixed per 1 mL MTT medium and incubated for 60 min at 37 ± 1 °C in the incubator (5 % CO2, 95 % RH).
- untreated MTT medium was used as control.
- after incubation verification of the colour by the unaided eye

TEST FOR COLOUR INTERFERENCE
- to check the colouring potential of the test item 30 µl of the test item were mixed per 300 µL aqua dest. and per 300 µL isopropanol each in a transparent recipient and incubated at 37 ± 1°C for 60 min (5 % CO2, 95 % RH).
- after incubation verification of the colour by the unaided eye

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 37 ± 1 °C for 35 ± 1 minutes followed by incubation at room temperature until the 60 ± 1 minute treatment period was completed
- Temperature of post-treatment incubation: 37 ± 1 °C

REMOVAL OF TEST MATERIAL AND CONTROLS
- after the end of the treatment period the tissues were washed 15 times with DPBS.
- subsequently, the inserts were submerged three times in DPBS and shaken to remove rests of the test item.
- then inserts were rinsed once from the inside and the outside with sterile DPBS.
- inserts were placed in prepared 6-well plates containing pre-warmed fresh assay medium per well.
- plates were post-incubated at 37 ± 1 °C, 5.0% CO2, humidified to 95%, for 24 ± 2 h. Following this incubation the tissues were transferred to new wells containing fresh assay medium and incubated for additional 18 ± 2 h.

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 1 mg/mL (300 µL/well)
- Incubation time: 3 hours ± 5 minutes
- Extraction of formazan: after the MTT incubation period, the tissues were rinsed three times with DPBS and allowed to dry. The tissues were transferred into 12-well plates and immersed in 2 mL isopropanol, sealed to inhibit evaporation. Extraction was carried out protected from light at room temperature at least for 2 hours with shaking on a plate shaker.
Before using the extracts, the plate had been shaken for at least 15 minutes on a plate shaker and the inserts were pierced with an injection needle. The extract was pipetted up and down 3 times before 2 x 200 µL aliquots per each tissue were transferred into a 96-well plate. Optical density (OD) was measured with a filter band without reference wavelength in a plate spectrophotometer using isopropanol as a blank.
- Wavelength: 570 nm
- Filter bandwidth: maximum ± 30 nm

FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
- Viability: tissues pass analysis for tissue viability
- Barrier function: tissues pass analysis for tissue functionality
- Morphology: presence of a functional stratum corneum, a viable basal cell layer, and intermediate spinous and granular layers.
- Contamination: absence of bacteria, yeast, and other fungi (long term antibiotic, antimycotic free culture) as well as absence of HIV1-virus, Hepatitis B virus and Hepatitis C virus
Please also refer to the field "Attached background material" below.

PREDICTION MODEL / DECISION CRITERIA
The mean optical density (OD) of the three negative control tissues was calculated after blank correction. This value corresponded to 100 % tissue viability in the current test. For each individual tissue treated with the test item or the positive control, the individual relative tissue viability is calculated according to the following formula:
Relative viability (%) = [(mean ODtest item / positive control) / ODmean of negative control] * 100
For the test item and the positive control the mean relative viability ± relative standard deviation of the three individual tissues were calculated and used for classification according to the following prediction model:
Irritant potential of the test item was predicted from the relative mean tissue viabilities compared to the negative control tissues concurrently treated with DPBS. The test item is considered to be irritant to skin in accordance with regulation EC 1272/2008 (UN GHS “Category 2”), if the tissue viability after exposure and post-incubation is less or equal to 50%. Further testing is required to resolve between UN GHS categories 1 and 2 and decide on the final classification of the test substance. The test substance may be considered as non-irritant to skin in accordance with regulation EC 1272/2008 and UN GHS “No Category” if the tissue viability after exposure and post-treatment incubation is more than 50%.
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 30 µl (47 mg/cm²) of the test item
Prior to treatment, all EpiDerm™ tissues were gently blotted to remove moisture. The test item was applied undiluted. 30 µL (47 µL/cm²) of the test item were dispensed directly atop the EpiDerm™ tissue. The test item was gently spread to match size of the tissue using a bulb-headed Pasteur pipette.

NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 30 µL DPBS

POSITIVE CONTROL
- Amount(s) applied (volume or weight): 30 µL of 5 % SDS solution
Duration of treatment / exposure:
60 ± 1 minute
Duration of post-treatment incubation (if applicable):
approx. 42 hours
Number of replicates:
triplicates
Irritation / corrosion parameter:
% tissue viability
Remarks:
(mean)
Value:
95.8
Vehicle controls validity:
not examined
Negative controls validity:
valid
Positive controls validity:
valid
Other effects / acceptance of results:
TEST FOR MTT INTERFERENCE
The mixture of 30 µL test item per 1 mL MTT medium showed no reduction of MTT compared to the solvent. The mixture did not turn blue/purple. Therefore, NSMTT equalled 0%.

TEST FOR COLOUR INTERFERENCE
The mixture of 30 µL of the test item per 300 µl aqua dest. and/or per 300 µL isopropanol showed no colouring detectable by unaided eye-assessment. Therefore, NSC equalled 0%.

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: mean absolute OD570 of the three negative control tissues was ≥ 0.8 and ≤ 2.8 (value: 1.849).
- Acceptance criteria met for positive control: mean relative tissue viability (% negative control) of the positive control was ≤ 20% (3.2 %)
- Acceptance criteria met for variability between replicate measurements: standard deviation of viability of replicate tissues of all dose groups was ≤ 18% (0.4 % - 6.3 %).
- The absorbance values were not below historically established boundaries.

Please also refer to the field "An other information on results incl. tables" below.

Table1:  Result of the test item zirconium, acetate lactate oxo ammonium complexes

Name

Negative Control

Positive Control

Test Item

Tissue

1

2

3

1

2

3

1

2

3

Absolute OD570

1.824

1.879

1.802

0.090

0.106

0.099

1.767

1.896

1.651

1.898

1.893

1.800

0.094

0.105

0.109

1.794

1.871

1.663

Mean Absolute OD570

1.849****

0.101

1.774

OD570(Blank Corrected)

1.781

1.836

1.759

0.047

0.063

0.056

1.724

1.853

1.608

1.855

1.849

1.757

0.051

0.062

0.066

1.751

1.828

1.620

Mean OD570of the Duplicates (Blank Corrected)

1.818

1.843

1.758

0.049

0.063

0.061

1.738

1.841

1.614

Total Mean OD570of 3 Replicate Tissues (Blank Corrected)

1.806*

0.058

1.731

SD OD570

0.044

0.007

0.113

Relative Tissue Viability [%]

100.6

102.0

97.3

2.7

3.5

3.4

96.2

101.9

89.4

Mean Relative Tissue Viability [%]

100.0

3.2**

95.8

SD Tissue Viability [%]

2.4***

0.4***

6.3***

CV [% Viabilities]

2.4

12.9

6.6

 

*Blank-corrected mean OD570 nmof the negative control corresponds to 100% absolute tissue viability.

**Mean relative tissue viability of the three positive control tissues is ≤ 20%

***Standard deviation (SD) of relative tissue viability obtained from the three concurrently tested tissues for test

item, positive control and negative control is 18%.

****Mean absolute OD570of the negative control tissues is0.8 and2.8.

Table2:  Historical data

 

Mean Absolute OD570±30nmNC

MeanAbsoluteOD570±30nmPC

Mean Relative Viability [%] PC

SD Viability [%]
NC, PC, TI

Mean

1.861

0.114

3.7

4.4

SD

0.247

0.033

1.5

4.1

Range of
LCL – UCL

1.367 – 2.355

0.048 – 0.181

0.7 – 6.8

0.0 – 12.5

n

25

25

25

117

LCL:      Lower control limit (95%, mean – 2*SD)

UCL:      Upper control limit (95%, mean + 2*SD)

n:            number of control values

Historical data were generated in 2017.


 


 

Interpretation of results:
GHS criteria not met
Conclusions:
In this study under the given conditions the test item, zirconium, acetate lactate oxo ammonium complexes, showed no irritant effects. The test item is therefore classified as “non-irritant” in accordance with UN GHS “No Category”.
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:
key study
Study period:
2018-05-03
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)
Version / remarks:
2017-10-09
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2015-06-05
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: ambient, tightly closed, store away from incompatible materials (e.g. strong oxidising agents)
Details on test animals or tissues and environmental conditions:
SOURCE OF COLLECTED EYES
- Source: abattoir A. Moksel AG, Buchloe, Germany
- Storage, temperature and transport conditions of ocular tissue: fresh eyes were collected from the slaughterhouse and were transported in HBSS containing Pen/Strep on ice to the laboratories
- Time interval prior to initiating testing: immediately after arrival of the eyes, cornea preparation was initiated and was used for BCOP testing on the same day.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent positive control
yes, concurrent negative control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 750 μL of the test substance
Duration of treatment / exposure:
10 minutes
Observation period (in vivo):
not applicable
Duration of post- treatment incubation (in vitro):
2 hours
Number of animals or in vitro replicates:
Number of bovine corneae per dose:
Test item: triplicates
Negative control: triplicates
Positive control: triplicates
Details on study design:
SELECTION AND PREPARATION OF CORNEAS
- eyes were examined for defects and any defective eyes were discarded. Eyes with scratches or any kind of opacity were not used.
- tissue surrounding the eyeball was pulled away and the cornea was excised.
- isolated corneas were stored in a petri dish containing HBSS. Before mounting the corneas in corneal holders (BASF, Duratec GmbH) with the endothelial side against the O-ring of the posterior chamber, they had been visually examined for defects and any defective cornea had been discarded. The anterior chamber was then positioned on top of the cornea and tightened with screws. The chambers of the corneal holder were then filled with pre-warmed RPMI (without phenol red) containing 1 % FBS and 2 mM L-glutamine (complete RPMI).
- corneas were incubated for one hour at 32 ± 1 °C for equilibration in an air incubator.

QUALITY CHECK OF THE ISOLATED CORNEAS
- after the equilibration period, the medium was removed from both chambers and replaced with fresh complete RPMI.
- an initial measurement was performed on each of the corneas using the opacitometer.
- three corneas with illuminance readings approximately equivalent to the median illuminance of all corneas were selected as negative-control corneas.
- the illuminance of each cornea was read and recorded.
- only corneas that had an initial illuminance reading I > I0/1.1651 lux (an equivalent to the opacity threshold of 7 as listed in OECD 437) were used for the assay.

APPLICATION DOSE AND EXPOSURE TIME
- medium was removed from the anterior chamber and replaced with the test item or control.
- 750 μL of the test substance or the control substance was introduced into the anterior chamber (closed-chamber method).
- after 10 minutes incubation at 32 ± 1 °C either the test substance or the control substance was removed.

REMOVAL OF TEST SUBSTANCE/CONTROL SUBSTANCES
- epithelium was washed at least three times with MEM (containing phenol red).
- once the medium was free of test substance, the cornea was finally rinsed with complete MEM (without phenol red).

METHODS FOR MEASURED ENDPOINTS:
- anterior chamber was refilled with complete MEM and an illuminance measurement was performed again after 2 hours incubation at 32 ± 1 °C
- each cornea was observed visually and pertinent observations were recorded.
- corneas were visually examined for tissue peeling, residual test chemical and non-uniform opacity patterns and observation were recorded.
- after the illuminance measurement was performed, the permeability was measured.
- the medium was removed from both chambers of the holder.
- posterior chamber was refilled with fresh complete RPMI.
- 1 mL of a 4 mg/mL sodium fluorescein solution was added to the anterior chamber and the corneas were incubated for 90 minutes at 32 ± 1 °C.
- then the medium from the posterior chamber was removed and its optical density at 490 nm (OD490) was determined, using a spectrophotometer (Jenway 6405 UV/VIS).

Evaluation of the opacity:
- the following formula was used to calculate the opacity, whereas the values a and b are equipment-specific variables empirically determined by the manufacturer:
Opacity = ((I0/I) - b)/ a
with a = 0.025 and b = 0.9894
- value I0 is the illuminance through a holder without cornea, but with windows and liquid. This value is determined by taking the mean for a set of cornea holders and is reevaluated periodically. This I0 value was than calculated to the respective data of the opacitometer and the data according to guideline (opacity < 7). So the initial illuminance could be calculated and corneas below this value were discarded.
- change in opacity for each cornea (test item, positive and negative control) was calculated by subtracting the initial opacity reading from the final opacity reading. These values of test item treated cornea or positive control were corrected by subtracting from each the average change in opacity observed for the negative-control corneas to obtain the corrected opacity. The mean corrected opacity value for the negtive control and the mean corrected opacity value for the test item and the positive control was calculated by averaging the corrected opacity values of each cornea for a given treatment.

Evaluation of the permeability:
- mean OD490 for the blank cuvettes was calculated.
- mean blank OD490 was subtracted from the OD490 of each cuvette (corrected OD490).
- any dilutions that were made to bring the OD490 values into the linear range of the spectrophotometer (OD490 should be less than 1.500), were taken into account by multiplying the OD490 value of the dilution by the dilution factor.
- final-corrected OD490 of the test article and the positive control were calculated by subtracting the average-corrected OD490 of the negative-control corneas from the corrected OD490 value of each treated cornea:
Final-corrected OD490 = (OD490 – mean blank OD490) – average-corrected negative control OD490
- mean OD490 value of each treatment group was calculated by averaging the final corrected OD490 values of the treated corneas for that treatment condition.

SCORING SYSTEM: In Vitro Irritancy Score (IVIS)
The following formula was used to determine the in vitro irritation score (IVIS):
IVIS = mean opacity value + (15 x mean permeability OD490 value)
To determine the IVIS of the positive control and the test item, the corrected opacity and OD490 values were used.

ACCEPTABILITY CRITERIA
- the BCOP assay is considered to be valid if the in vitro irritation score obtained with the positive control falls within the two standard deviations of the current historical mean.
- the negative control responses should result in opacity and permeability values that are less than the established upper limits for background bovine corneas treated with the respective negative control.
Irritation parameter:
in vitro irritation score
Remarks:
(mean)
Value:
2.09
Vehicle controls validity:
not examined
Negative controls validity:
valid
Positive controls validity:
valid
Other effects / acceptance of results:
Visual Observation after treatment:
None of the 3 corneas treated with Zirconium, acetate lactate oxo ammonium complexes showed any opacity of the tissue.

Measurement after treatment:
Relative to the negative control, the test item caused no increase of corneal opacity and permeability in all 3 corneas.

Acceptance of results:
The test is valid since the IVIS of the positive control falls within two standard deviations of the current historical mean and opacity and permeability of the negative control are less than the respective established upper limits for background opacity and permeability.

Table 1: Opacity

Cornea
No.

Test Item

Initial
Opacity

Final
Opacity

Change of
Opacity Value

Corrected
Opacity Value

1

Negative
Control

0.32

0.32

0.00

 

2

0.32

0.70

0.38

 

3

0.52

0.49

-0.03

 

MV

0.39

0.50

0.11

 

4

Positive
Control

1.65

23.97

22.32

22.21

5

1.22

23.37

22.15

22.04

6

0.90

19.56

18.66

18.54

MV

1.26

22.30

21.04

20.93

7

Test Item

-0.11

1.65

1.76

1.65

8

-0.15

1.01

1.16

1.04

9

-0.57

2.65

3.22

3.11

MV

-0.28

1.77

2.05

1.93

MV = mean value

Table 2: Permeability

Cornea
No.

Test Item

OD490

Corrected
OD490 Value

1

Negative
Control

0.002

 

2

0.008

 

3

0.001

 

MV

0.004

 

4

Positive
Control

1.292

1.288

5

1.472

1.468

6

1.454

1.450

MV

1.406

1.402

7

Test Item

0.013

0.009

8

0.018

0.014

9

0.011

0.007

MV

0.014

0.010

MV = mean value

Table 3:  In vitro irritation score

Cornea
No.

Test Item

Corrected
Opacity Value

Corrected
OD490 Value

IVIS

1

Negative
Control

0.00

0.002

 

2

0.38

0.008

 

3

-0.03

0.001

 

MV

0.11

0.004

0.17

4

Positive
Control

22.21

1.288

 

5

22.04

1.468

 

6

18.54

1.450

 

MV

20.93

1.402

41.96

7

Test Item

1.65

0.009

 

8

1.04

0.014

 

9

3.11

0.007

 

MV

1.93

0.010

2.09

MV = mean value

Table 4: Historical mean in vitro irritation score of the positive control (ethanol 100%) from February 2015 until May 2018

 

IVIS
Positive Control - Ethanol 100 %

Mean Value (MV)

48.35

Standard Deviation (SD)

9.56

MV- 2xSD

29.22

MV+2xSD

67.47

Number of Replicates providing Historical Mean: 52

Positive controls are updated after every single experiment or at least every 3 months

Positive controls are updated after every single experiment or at least every 3 months.

Table 5: Historical data on opacity and permeability of the positive control (ethanol 100%) from August 2017 until May 2018

Number of Replicates Providing Historical Mean

Cornea No.

Opacity

Permeability

IVIS

Change of
Opacity Value

Corrected
Opacity Value

OD490 Value

Corrected
OD490 Value

1

4

37.495

37.899

1.013

1.004

53.36

5

27.335

27.739

1.147

1.138

6

30.218

30.622

2.120

2.111

2

4

24.492

23.921

1.442

1.436

49.70

5

31.754

31.182

1.108

1.102

6

30.259

29.688

1.755

1.749

3

4

40.460

39.546

1.270

1.266

49.84

5

28.925

28.010

0.949

0.945

6

29.064

28.149

1.381

1.377

4

4

22.710

22.292

1.182

1.178

52.16

5

35.986

35.567

1.780

1.776

6

24.036

23.618

2.050

2.046

6

4

25.61

24.97

2.025

2.014

63.38

5

28.89

28.25

2.920

2.909

6

27.82

27.18

2.405

2.394

7

4

22.66

21.94

1.407

1.399

42.08

5

22.03

21.31

1.354

1.346

6

22.31

21.60

1.355

1.347

8

4

31.80

31.03

0.985

0.958

42.99

5

27.64

26.87

1.166

1.139

6

27.22

26.45

0.905

0.878

9

4

22.32

22.21

1.292

1.288

41.96

5

22.15

22.04

1.472

1.468

6

18.66

18.54

1.454

1.450

Mean Value (MV)

27.577

27.110

1.497

1.488

49.43

Standard Deviation (SD)

5.354

5.364

0.500

0.502

7.26

MV- 2xSD

16.869

16.383

0.497

0.485

34.91

MV+2xSD

38.285

37.837

2.498

2.492

63.95

Table 6:  Historical mean in vitro irritation score of the negative control (NaCl 0.9 %) from February 2015 until May 2018

 

IVIS Negative Control - NaCl 0.9 %

Mean Value (MV)

0.80

Standard Deviation (SD)

0.64

MV- 2xSD

-0.47

MV+2xSD

2.08

Number of Replicates providing Historical Mean: 52

Negative controls are updated after every single experiment or at least every 3 months.

Table 7:  Historical data on opacity and permeability of the negative control (NaCl 0.9 %) from August 2017 until May 2018

Replicates Providing Historical Mean

Cornea No.

Opacity

Permeability

IVIS

Change of
Opacity Value

OD490 Value

1

1

-0.57

0.009

-0.27

2

-0.11

0.013

3

-0.53

0.004

2

1

-0.25

0.004

0.66

2

0.80

0.005

3

1.17

0.008

3

1

0.11

0.004

0.48

2

0.68

0.005

3

0.47

0.003

4

1

0.19

0.008

0.18

2

-0.12

0.005

3

0.00

0.018

 

1

0.11

0.005

 

5

2

0.74

0.022

0.81

 

3

1.06

0.007

 

6

1

0.26

0.011

 

2

1.21

0.004

0.83

3

0.68

0.008

 

 

1

0.50

0.022

 

7

2

0.75

0.045

1.18

 

3

1.05

0.015

 

 

1

1.09

0.006

 

8

2

0.60

0.017

1.19

 

3

1.47

0.004

 

 

1

0.00

0.002

 

9

2

0.38

0.008

0.17

 

3

-0.03

0.001

 

Mean Value (MV)

0.43

0.01

0.58

Standard Deviation (SD)

0.55

0.01

0.49

MV- 2xSD

-0.66

-0.01

-0.40

MV+2xSD

1.53

0.03

1.56

Interpretation of results:
GHS criteria not met
Conclusions:
In conclusion, according to the current OECD 437 study and under the experimental conditions reported, Zirconium, acetate lactate oxo ammonium complexes is not eye irritating (EU CLP/ UN GHS Category 2) and not serious eye damaging (EU CLP/ UN GHS Category 1). The test item should not be classified according to Regulation (EC) No 1272/2008 and subsequent adaptations.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

The substance was not observed to be a skin irritant in a reliable in vitro skin irritation study according to OECD 439.

Eye irritation:

The substance was not observed to be an eye irritant in a reliable in vitro eye irritation study according to OECD 437.

Justification for classification or non-classification

Skin irritation

The substance does not possess a skin irritation potential based on an in vitro OECD 439 test and does not require classification as skin irritant according to Regulation (EC) No 1272/2008 and its subsequent adaptations.

Eye irritation

The substance does not possess an eye irritation potential based on an in vitro OECD 437 test and does not require classification as eye irritant according to Regulation (EC) No 1272/2008 and its subsequent adaptations.