(R)-6-(isopropyl)-3-methylcyclohex-2-en-1-one

Endpoint summary

Description of key information

Skin irritation (OECD 439 and 431): irritating

Eye irritation (OECD 405): irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 June - 15 July 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

/ no application of correction factor on positive control, no demonstration of technical proficiency, 3 min incubation at room temperature instead of at 37°C (OECD 431)

Qualifier:

according to guideline

Guideline:

OECD Guideline 431 (In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method)

Version / remarks:

29 July 2016

Deviations:

yes

Remarks:

/ no application of correction factor on positive control, no demonstration of technical proficiency, 3 min incubation at room temperature instead of at 37°C (OECD 431)

Qualifier:

according to guideline

Guideline:

other: EU method B.40 BIS. (In Vitro Skin Corrosion: Human Skin Model Test)

Version / remarks:

30 May 2008

Deviations:

yes

Remarks:

/ no demonstration of technical proficiency

GLP compliance:

yes (incl. QA statement)

Remarks:

Hess. Ministerium für Umwelt, Klimaschutz, Landwirtschaft und Verbrauchersch utz, Wiesbaden, Germany

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Source strain:

other: EpiDermTM; reconstructed three-dimensional human epidermis (EPI-200); 00267

Justification for test system used:

The normal, human-derived epidermal keratinocytes (NHEK) attain levels of differentiation at the cutting edge of in vitro skin technology. Ultrastructurally, the skin models closely parallel human skin.

Vehicle:

unchanged (no vehicle)

Details on test system:

RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EpiDerm™ Kit (Epi-200, MatTek Corporation (Bratislava, Slovakia)
- Tissue lot number: 23345
- Delivery date: 12 June 2016
- Date of initiation of testing: 27 June 2016

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: room temperature for the 3 ± 0.5 min exposure periods, 37 ± 1.5 °C for the 60 ± 5 min exposure period

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: rinsed 20 times with DPBS
- Observable damage in the tissue due to washing: no
- Modifications to validated SOP: no

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 1mg/mL
- Incubation time: 3 h
- Spectrophotometer: microplate reader (Versamax®, Molecular Devices, SoftMax Pro Enterprise (version 4.7.1))
- Wavelength: 570 nm

FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
- Viability: OD = 1.783 ± 0.027 (Acceptance criteria: 1.0-3.0)
- Barrier function: ET-50 = 6.16 h (Acceptance criteria: 4.77 - 8.72)
- Morphology: functional stratum corneum, a viable basal cell layer and intermediate spinous and granular layers
- Contamination: no contamination

NUMBER OF REPLICATE TISSUES: duplicate

CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE
- Killed tissues
- Procedure used to prepare the killed tissues: freezing
- N. of replicates : 2
- Method of calculation used: True viability = Viability of treated tissue – Interference from test chemical = ODtvt – ODkt; ODkt = (mean ODtkt – mean ODukt)
tvt = treated viable tissue
kt = killed tissues
tkt = treated killed tissue
ukt = untreated killed tissue (NC treated tissue)
Since the interference by the test item extract is < 30% of the negative control value, the net OD of the test item extract treated killed control was subtracted from the mean OD of the test item extract treated viable tissues to obtain the true amount of MTT reduction that reflects metabolic conversion only.

NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 2

PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
- The test substance is considered to be corrosive to skin if the viability after 3 minutes exposure is less than 50% (optional Sub-category 1A), or if the viability after 3 minutes exposure is greater than or equal to 50 % and the viability after 1 hour exposure is less than 15% (optional Sub-category 1B and 1C).
- The test substance is considered to be non-corrosive to skin if the viability after 3 minutes exposure is greater than or equal to 50% and the viability after 1 hour exposure is greater than or equal to 15%.

Control samples:

yes, concurrent negative control

yes, concurrent positive control

yes, concurrent MTT non-specific colour control

Amount/concentration applied:

TEST MATERIAL
- Amount(s) applied: 50 µl
- Concentration: 79.4 μL/cm2

NEGATIVE CONTROL
- Amount(s) applied: 50 μL

POSITIVE CONTROL
- Amount(s) applied (volume or weight): 50 μL
- Concentration: 8 N

Duration of treatment / exposure:

3 ± 0.5 min and 60 ± 5 min

Number of replicates:

2

Type of coverage:

other: in vitro system

Preparation of test site:

other: intact reconstructed human epidermis

Vehicle:

unchanged (no vehicle)

Irritation / corrosion parameter:

% tissue viability

Remarks:

of negative control

Run / experiment:

mean value of the test item (100%), 3 min exposure

Value:

114

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation / corrosion parameter:

% tissue viability

Remarks:

of negative control

Run / experiment:

mean value of the test item (100%), 60 min exposure

Value:

56.7

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

- OTHER EFFECTS:
- Visible damage on test system: no
- Direct-MTT reduction: yes
- Colour interference with MTT: no

DEMONSTRATION OF TECHNICAL PROFICIENCY: no

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes, as the mean OD of the tissue replicates treated with the negative control is ≥ 0.8 and ≤ 2.8 for every exposure time (values between 1.693 and 1.924)
- Acceptance criteria met for positive control: yes, as the mean viability of the tissue replicates treated with the positive control for 1 hour, is <15% compared to the negative control (7.9%)
- Acceptance criteria met for variability between replicate measurements: yes, as the Coefficient of Variation (CV) is in the range of 20 – 100% viability between tissue replicates is ≤ 30% (values between 3.8% and 16.6%)

Table 1: MTT assay after 3 min exposure

	Negative control		Positive control		Test item
Tissue sample	1	2	1	2	1	2
OD570	1.795	1.775	0.594	0.647	2.276	2.062
	1.820	1.717	0.603	0.685	2.019	1.944
	1.850	1.693	0.619	0.658	2.002	1.949
OD570(mean)	1.821	1.728	0.606	0.663	2.099	1.985
OD570(mean values* of replicates)	1.737		0.597		2.005
CV (%)	3.8		6.8		4.0
rel. viability (%)	100.0		34.4		114.0**

Blanc (mean) = 0.038

* after blanc correction of single values

** after data correction because of MTT interference

CV = Coefficient of Variation

Table 2: MTT assays after 60 min exposure

	Negative control		Positive control		Test item
Tissue sample	1	2	1	2	1	2
OD570	1.924	1.845	0.198	0.158	1.232	0.968
	1.895	1.715	0.184	0.166	1.181	0.949
	1.768	1.728	0.184	0.167	1.190	0.951
OD570(mean)	1.862	1.763	0.189	0.164	1.201	0.956
OD570(mean values* of replicates)	1.776		0.140		1.042
CV (%)	4.0		12.6		16.6
rel. viability (%)	100.0		7.9		56.7**

Blanc (mean) = 0.038

* after blanc correction of single values

** after data correction because of MTT interference

CV = Coefficient of Variation

Interpretation of results:

other: not corrosive

Conclusions:

The test item PIPERITONE was non corrosive to skin according to EU CLP and UN GHS

Executive summary:

After exposure of the tissues to the test item the relative absorbance value did not decrease (114.0%) after 3 minutes exposure. After the 1 hour exposure the viability was reduced to 56.7%. The correction factor derived from the additional test with freeze-killed tissues was considered. Both values did not affect the threshold for corrosivity which is defined to be 50% after the 3 minutes exposure and 15% after the 1 hour exposure. Therefore, the test item was not considered to be corrosive.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04 May - 06 June 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)

Version / remarks:

28 July 2015

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)

Version / remarks:

Commission Regulation 440/2008, 1st ATP 2009

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Hess. Ministerium für Umwelt, Klimaschutz, Landwirtschaft und Verbraucherschutz, Wiesbaden, Germany

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Source strain:

other: EpiDerm™; Reconstructed Human Epidermal Model (EPI-200), Strain 00267, Lot Nr 23339

Details on animal used as source of test system:

SOURCE ANIMAL
- Source: MatTek Corporation, Bratislava, Slovakia

The EpiDerm™ tissue consists of normal, human-derived epidermal keratinocytes which have been cultured to form a multilayered, highly differentiated model of the human epidermis. It consists of organized basal, spinous and granular layers, and a multi-layered stratum corneum containing intercellular lamellar lipid layers arranged in patterns analogous to those found in vivo.

Justification for test system used:

Systemic reactions play a minor role in modulating local skin toxicity potential of chemicals, so skin irritation potential may be predicted by in vitro systems, provided they are sufficiently complex to mimic human skin barrier and cell reactivity.

Vehicle:

unchanged (no vehicle)

Details on test system:

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 37 ± 1.5 °C
- Temperature of post-treatment incubation (if applicable): room temperature, later again 37 ± 1.5 °C

REMOVAL OF TEST MATERIAL AND CONTROLS
- Number of washing steps: at least 15

DYE BINDING METHOD
- Dye used in the dye-binding assay: MTT
- Spectrophotometer: microplate reader (Versamax® Molecular Devices, Softmax Pro, version 4.7.1)
- Wavelength: 570 nm

NUMBER OF INDEPENDENT TESTING RUNS / EXPERIMENTS TO DERIVE FINAL PREDICTION: One experiment was carried out in triplicate plating.

PREDICTION MODEL / DECISION CRITERIA
- The test substance is considered to be irritant to skin if the mean relative tissue viability of three individual tissues is reduced to ≤ 50% of the negative control.
- The test substance is considered to be non-irritant to skin if the mean relative tissue viability of three individual tissues is > 50% of the negative control.

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

TEST MATERIAL
- Amount(s) applied: 30 μL
- Concentration (if solution): 47 μL/cm²

NEGATIVE CONTROL
- Amount(s) applied: 30 μL

POSITIVE CONTROL
- Amount(s) applied (volume or weight): 30 μL
- Concentration (if solution): 5% SLS

Duration of treatment / exposure:

1 h

Duration of post-treatment incubation (if applicable):

43 h

Number of replicates:

3

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

mean value of test item (47 μL/cm²)

Value:

4.8

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

- OTHER EFFECTS:
- Direct-MTT reduction: No. The test item did not reduce MTT (test for direct MTT reduction).
- Colour interference with MTT: No. The test item did not change colour when mixed with deionised water (test for colour interference). Also its intrinsic colour was not intensive.

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: After treatment with the negative control the absorbance values (1.525, 1.957, 1.950) were in the range of the required acceptability criterion of mean OD ≥ 0.8 and ≤ 2.8 for the 60 min treatment.
- Acceptance criteria met for positive control: Exposure to the positive control induced a decrease in the relative absorbance as compared to the negative control to 4.3% thus confirming the validity of the test system.
- Acceptance criteria met for variability between replicate measurements: yes, but value (19%) is slightly above the threshold of the OECD Guideline 439 ( < 18%)

Table 2: MTT assay after 60 min exposure

Dose Group	Tissue No.	OD570			OD570(mean absorbance of replicates)	Mean absorbance of replicates blank corrected	Mean absorbance of replicates after blank correction	Rel. Absorbance [%] Tissue 1, 2 + 3*	Relative Standard Deviation [%]	Viability (Mean Rel. Absorbance [% of Negative Control]***)
		Well 1	Well 2	Well 3
Blank		0.036	0.037	0.036	0.036
Negative Control	1	1.578	1.549	1.558	1.562	1.525	1.811	84.2	13.7	100.0
	2	2.026	1.984	1.971	1.994	1.957		108.1
	3	2.024	1.971	1.965	1.986	1.950		107.7
Positive Control	1	0.098	0.097	0.097	0.097	0.061	0.078	3.4	19.0	4.3
	2	0.118	0.121	0.118	0.119	0.082		4.6
	3	0.125	0.126	0.126	0.126	0.089		4.9
Test Item	1	0.135	0.137	0.133	0.135	0.098	0.087	5.4	11.6	4.8
	2	0.117	0.116	0.116	0.116	0.080		4.4
	3	0.119	0.119	0.118	0.119	0.082		4.5

* = relative absorbance per tissue [rounded values]: 100 x (absorbance tissue)/(mean adsorbance negative control)

** = relative absorbance per treatment group [rounded values]: 100 x (mean absorbance test item/ positive control)/(mean adsorbance negative control)

Interpretation of results:

other: irritating potential (Skin Irrit. 2 or Skin Corr. 1 according to Regulation (EC) No 1272/2008)

Conclusions:

Under the conditions of the test, the test substance was shown to have an irritating potential towards reconstructed human epidermis tissue in the EpiDerm™ model.

Executive summary:

The skin irritation potential of the test substance was determined by an in vitro skin irritation test using a reconstructed human skin model according to OECD Guideline 439 and in compliance with GLP (2016).

After treatment with the test substance for 60 min the tissue viability decreased to 4.8% compared to the negative control (threshold for irritancy ≤ 50%). Therefore, the test substance is considered to possess an irritant potential.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (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:

26 June - 04 July 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

/ GLP guideline study with minor deviations (no information about animal age, body weight determined only once)

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

02 Oct 2012

Deviations:

yes

Remarks:

/ GLP guideline study with minor deviations (no information about animal age, body weight determined only once)

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

30 May 2008

Deviations:

yes

Remarks:

/ GLP guideline study with minor deviations (no information about animal age, body weight determined only once)

GLP compliance:

yes

Species:

rabbit

Strain:

other: SPF albino rabbits, Chbb:HM(SPF) - Littlerussian

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: BI Pharma KG, Biberach, Germany
- Weight at study initiation: 1.5 - 1.7 kg (females)
- Housing: individual in PPO cages with perforated floor
- Diet : pelleted diet Altromin 2123 (Altromin, Lage, Lippe Germany), ad libitum
- Water: water (acidified with hydrochloric acid, pH 2,5), ad libitum (analysis was performed)
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/ 12

IN-LIFE DATES: From: 26 June To: 04 July 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 of the test article were applied into one eye of the rabbits.

Duration of treatment / exposure:

single application without washing

Observation period (in vivo):

7 days
Reading time points: 1, 24, 48, 72 h and 7 days after the treatment

Number of animals or in vitro replicates:

4 females

Details on study design:

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Remarks:

before fluorescein application

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Remarks:

before fluorescein application

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 3 days

Irritation parameter:

cornea opacity score

Remarks:

before fluorescein application

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible within: 3 days

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible within: 3 days

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible within: 3 days

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.7

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

Based on the readings before fluorescein application, all 4 animals showed a cornea opacity (scored with 1) after 1h , which was reversible within 72 h in 1/4 animals. All animals showed an Iris score of 1 after 1 h, which was reversible within 72h in 2/4 animals. Conjunctivae was observed in all animals after 1 h (scored with 3 in 1 animal and with 2 in the other 3 animals). After 24 h all animals showed a conjunctivae scored with 2. After 48 h or 72 h the scoring decreased to 1 (in 2 or 1 animal, respectively). The fourth animal showed a consistent scoring of 2 within the 72 h. Chemosis was observed in all animals after 1 h (scored with 2). 2/2 animals showed a decrease in scoring to 1 after 24 h, the other 2 animals after 48 h.
7 days after application of the test article all four animals were free of any signs of eye irritation.

Table 1: Individual scores of eye irritation

Rabbit #	Time [h]	conjunctivae		iris	cornea	cornea (after Fluorescein)
		redness	chemosis (swelling)
1	1	3	2	1	1	-
	24	2	2	1	1	1
	48	2	1	1	1	1
	72	1	1	0	1	1
	mean	1.7	1.3	0.7	1.0	1.0
2	1	2	2	1	1	-
	24	2	1	1	1	1
	48	1	1	1	1	1
	72	1	1	0	0	1
	mean	1.3	1.0	0.7	0.7	1.0
3	1	2	2	1	1	-
	24	2	2	1	1	1
	48	2	1	1	1	1
	72	2	1	1	1	0
	mean	2.0	1.3	1.0	1.0	0.7
4	1	2	2	1	1	-
	24	2	1	1	1	1
	48	1	1	1	1	1
	72	1	1	0	1	1
	mean	1.3	1.0	0.7	1.0	1.0

Iris: 0 - 2 numerical scores, Redness: 0 - 3 numerical scores, Chemosis and Cornea opacity score : 0 - 4 numerical scores

 

Only the scores from the readings after 24, 48 and 72 hours are included in the calculation of the individual mean scores.

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

CLP: Eye irrit 2, H319

Executive summary:

The eye irritation potential of the test substance was determined by an in vivo eye irritation test according to OECD Guideline 405 and in compliance with GLP (2016).Application of the test substance to the rabbit eye resulted in a mean corneal opacity score of 1 in 3/4 animals, which was reversible within maximum 7 days. Thus, the test substance is considered to be irritant to the eye.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin

The skin irritation potential of the test substance was determined by an in vitro skin irritation test using a reconstructed human skin model according to OECD Guideline 439 and in compliance with GLP (2016).

After treatment with the test substance for 60 min the tissue viability decreased to 4.8% compared to the negative control (threshold for irritancy ≤ 50%). Therefore, the test substance is considered to possess an irritant potential.

The skin corrosive potential of the test substance was determined by an in vitro skin irritation test using a reconstructed human skin model according to OECD Guideline 431 and in compliance with GLP.

After exposure of the tissues to the test item the relative absorbance value did not decrease (114.0%) after 3 minutes exposure. After the 1 hour exposure the viability was reduced to 56.7%. The correction factor derived from the additional test with freeze-killed tissues was considered. Both values did not affect the threshold for corrosivity which is defined to be 50% after the 3 minutes exposure and 15% after the 1 hour exposure. Therefore, the test item was not considered to be corrosive.

In conclusion, based on available studies, the test substance is considered to be irritating to the skin and therefore is classified as Skin Irrit. 2, H315 according to CLP.

Eye

The eye irritation potential of the test substance was determined by an in vivo eye irritation test according to OECD Guideline 405 and in compliance with GLP (2016). Application of the test substance to the rabbit eye resulted in a mean corneal opacity score of 1 in 3/4 animals, which was reversible within maximum 7 days. Thus, the test substance is considered to be irritant to the eye.

Justification for classification or non-classification

The available data on skin irritation meet the criteria for classification as Skin Irrit. Cat. 2 (H315) according to Regulation (EC) 1272/2008.

The available data on eye irritation meet the criteria for classification as Eye Irrit. Cat. 2 (H319) according to Regulation (EC) 1272/2008.