4'-bromo-3-chloropropiophenone

Endpoint summary

Description of key information

For the assessment of irritation / corrosion in vitro methods have been applied. The following results have been obtained:

Skin irritation

OECD 439: Category 2 or 1

OECD 431: not corrosive

Based on the weight of evidence approach the test item is considered to be irritating to skin.

Eye irritation

OECD 492: Category 2 or 1

OECD 437: not predictable

The test item showed an irritating/corrosive potential to eye. Since corrosivity to the eye cannot be excluded, the test item is considered to be corrosive to eye for precautionary reasons. 

Respiratory tract irritation

There are currently no validated tests on respiratory tract irritation, however, it is a reasonable precaution to assume that corrosive (and severely irritating) substances would also cause respiratory tract irritation. Since the substance induced serious eye damage, it is assumed as a precautionary measure that the test item cause also respiratory tract irritation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Feb 26 - May 08, 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Council Regulation (EC) No. 761/2009 laying down test methods pursuant to Regulation (EC) No. 1907/2006 of the European Parliament and the council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH).

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2010

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Skinethic skin irritation test -42bis Standard operating procedure (SOP) 2009

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
No pre-treatment; the test item was applied undiluted.

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Cell source:

other: normal, human-derived epidermal keratinocytes

Justification for test system used:

standard model

Vehicle:

unchanged (no vehicle)

Remarks:

No vehicle used in this study; The test item was applied neat to the tissues.

Details on test system:

CELL CULTURE
- Supplier:MatTek Corporation (82105 Bratislava, Slovakia)
- Source: normal, human-derived epidermal keratinocytes which have been cultured to form a multilayered, highly differentiated model of the human epidermis
- Format: 24 well plate
- Batch: 30854


TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment: room temperature
- Temperature of post-treatment incubation: 37°C

REMOVAL OF THE TEST MATERIAL AND CONTROL
After the end of the treatment interval, the residual test item was removed immediately by gently rinsing with a minimum volume of 25 mL PBS using a pipette. Excess PBS was removed by gently shaking the inserts and blotting the bottom with blotting paper.

DYE BINDING METHOD
- Dye used in the dye-binding assay: MTT
- Spectrophotometer:Versamax® Molecular Devices (570 nm)

Control samples:

yes, concurrent negative control

Amount/concentration applied:

TEST MATERIAL: 25 mg of solid test material
NEGATIVE CONTROL: 25 µL Phosphate-Buffered Saline
POSITIVE CONTROL: 25 µL (5% aqueous solution of sodium dodecyl sulfate in deionised water)

Duration of treatment / exposure:

60 min (± 1 minute); 35 min in incubator and 25 min sterile bench at room temperature

Number of replicates:

3

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

Experiment 1 / Run 1

Value:

15.73

Vehicle controls validity:

not applicable

Remarks:

The test item was applied neat to the tissues

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

positive indication of irritation

Other effects / acceptance of results:

OTHER EFFECTS:
- Visible damage on test system: none
- Direct-MTT reduction: none
- Colour interference with MTT: none

Acceptability of the Positive and Negative Control
After treatment with the negative control the absorbance values were well within the required range of the acceptability criterion of mean OD ≥ 0.8 and ≤ 2.8 for the 60 minutes treatment interval, thus assuring the quality of the tissues.
Treatment with the positive control induced a decrease in the viability compared with the negative control to 3.40%, thus ensuring the validity of the test system.
The standard deviations between the three tissue percentage viability values of each group (test item, positive and negative controls) in the main test were below 18 (threshold according OECD 439: ≤ 18), thus ensuring the validity of the study.

Group	Time / [min]	Mean OD	Mean Relative viability / [%]
Negative Control	60	1.902	100
Positive Control	60	0.065	3.40
Test Material	60	0.229	2.80

Interpretation of results:

other: UN GHS/ EU CLP “Category 2” or “Category 1”

Conclusions:

Under the experimental conditions reported, the test item is irritant to skin. The test item is identified as requiring classification and labelling according to UN GHS/ EU CLP “Category 2” or “Category 1”, since the tissue viability after exposure and post-incubation is less or equal to 50%.

Executive summary:

 

Objective

The objective of the present study was to investigate the potential of the test item to induce skin irritation in an in vitro human skin model.

Methods

The information for this endpoint study record was obtained from an experimental study. The OECD GLP criteria were met and the methods applied are fully compliant with OECD TG 439. The test item was applied topically to a human reconstructed skin model followed by determination of the cell viability. Cell viability was determined by enzymatic conversion of vital dye MTT into a blue formazan salt and measurement of the formazan salt after extraction from tissues. The percent reduction of cell viability in comparison to untreated negative controls was used to predict the skin irritation potential.
Triplicates of the human skin model were treated with the test item, the negative or the positive control for 60 minutes (± 1 minute). 25 µL of either the negative control (DPBS-buffer) or the positive control (5% aqueous solution of sodium dodecyl sulfate) were applied to the tissues. Before application of 25 mg of the solid test item, 10 µL of deionised water was spread to the epidermis surface to improve the contact between the test item and the epidermis.

Result

The test item did not prove to be a MTT reducer in the MTT interference pre-experiment. Also, its intrinsic color was not intensive and it did not change color when mixed with deionised water or isopropanol. Therefore, additional tests with freeze-killed tissues or viable tissues (without MTT addition) did not have to be performed.

Each three tissues of the human skin model EpiDerm™ were treated with the test item, the negative control (DPBS) or the positive control (5% SDS) for 60 minutes.

After treatment with the negative control the absorbance values were well within the required range of the acceptability criterion of mean OD ≥ 0.8 and ≤ 2.8 for the 60 minutes treatment interval, thus assuring the quality of the tissues.

Treatment with the positive control induced a sufficient decrease in the viability as compared to the negative control for the 60 minutes treatment interval, thus assuring the validity of the test system.

After treatment with the test item the mean relative viability value was 15.73% compared to the relative absorbance value of the negative control. This value is below the threshold for irritancy of ≤ 50%. Therefore, the test item is considered to possess an irritant potential.

Conclusion

Under the experimental conditions reported, the test item is irritant to skin. The test item is identified as requiring classification and labelling according to UN GHS/ EU CLP “Category 2” or “Category 1”, since the tissue viability after exposure and post-incubation is less or equal to 50%.

Reference 2

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

May 04 - Aug 03, 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: Council Regulation (EC) No. 440/2008 laying down test methods pursuant to Regulation (EC) No. 1907/2006. B.40.bis. In vitro skin corrosion: human skin model test

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

July 29, 2016

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: INVITTOX Protocol SkinEthic Skin Corrosivity Test, April 2012.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Cell source:

other: normal, human-derived epidermal keratinocytes which have been cultured to form a multilayered, highly differentiated model of the human epidermis

Justification for test system used:

standard model

Vehicle:

unchanged (no vehicle)

Remarks:

No vehicle used in this study; The test item was applied neat to the tissues.

Details on test system:

CELL CULTURE
- Supplier: MatTek Corporation (Bratislava, Slovakia)
- Source: normal, human-derived epidermal keratinocytes which have been cultured to form a multilayered, highly differentiated model of the human epidermis
- Format: 24 well plate
- Batch: 30869


TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment: room temperature
- Temperature of post-treatment incubation: 37°C

REMOVAL OF THE TEST MATERIAL AND CONTROL
At the end of the exposure periods, the test item, positive and negative control was removed immediately by gently rinsing with a minimum volume of 20 mL DPBS using a pipette. Excess DPBS was removed by gently shaking the tissue inserts and blotting the bottom of the tissue inserts with blotting paper.

Control samples:

yes, concurrent negative control

Amount/concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 25 mg of solid test material
- Concentration (if solution): n/a

VEHICLE
- Amount(s) applied (volume or weight with unit): n/a
- Concentration (if solution): n/a
- Lot/batch no. (if required): n/a
- Purity: n/a

NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 25 µL µl (DPBS)
- Concentration (if solution): n/a

POSITIVE CONTROL
- Amount(s) applied (volume or weight): 25 µL µl
- Concentration (if solution): An 8N potassium hydroxide solution dissolved deionised water pure was used as positive control.

Duration of treatment / exposure:

3 min & 1 hour

Number of replicates:

2

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

Experiment 1 / Run 1 (3 min)

Value:

86.83

Vehicle controls validity:

not applicable

Remarks:

The test item was applied neat to the tissues

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: Non-corrosive

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

Experiment 1 / Run 1 (1 hour)

Value:

70.83

Vehicle controls validity:

not applicable

Remarks:

The test item was applied neat to the tissues

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: Non-corrosive

Other effects / acceptance of results:

OTHER EFFECTS:
- Visible damage on test system: none
- Direct-MTT reduction: none
- Colour interference with MTT: none

ACCEPTANCE OF RESULTS:

Acceptability of the Quality Control Data of the Skin Model with Reference to Historical Batch Data:

Acceptance Criterion Result
Negative control OD ≥ 0.8 and ≤ 2.8 1.788 - 2.048

Mean viability positive control < 15% after 1-hour exposure 19.2% ( 3 min)
6.08 % (1 h)

The study met all acceptance criteria.

Group	Time / [min]	Mean OD	Mean Relative viability / [%]
Negative Control	3	2.048	100.0
Negative Control	60	1.788	100.0
Positive Control	60	0.109	6.08
Test Material	3	1.778	86.83
Test Material	60	1.267	70.83

Interpretation of results:

GHS criteria not met

Remarks:

Non-corrosive

Conclusions:

This study was performed according to GLP and the methods applied are fully compliant with OECD TG 431. Under the conditions of the present study, the test item is not considered to possess a corrosive potential to skin.

Executive summary:

 

Objective

The objective of the present study was to investigate the potential of the test item to induce skin corrosion in anin vitrohuman skin model.

 

Study Design

The test item was applied topically to a human reconstructed skin model followed by determination of the cell viability. Cell viability was determined by enzymatic conversion of vital dye MTT into a blue formazan salt and measurement of the formazan salt after extraction from tissues. The percent reduction of cell viability in comparison to untreated negative controls was used to predict the skin corrosion potential.

 

Duplicates of the human EpiDerm skin model were treated with the test item or the negative control for 3 minutes and additional 1 hour. Duplicates with the positive control were only treated for
1 hour. 25 µL of either the negative control (DPBS) or the positive control (potassium hydroxide, 8N) were applied to the tissues. Before application of 25 mg of the solid test item, 25 µL of deionised water was spread to the epidermis surface to improve the contact between the test item and the epidermis.

 

Results

Independent duplicate tissues of EpiDerm™ were exposed to either the test item, the negative control (Dulbecco's Phosphate-Buffered Saline (DPBS)) or the positive control (8.0 N KOH) for 3 minutes and 1 hour, respectively.

After exposure to the negative control the absorbance values met the required acceptability criterion of a mean OD570 ≥ 0.8 and ≤ 2.8 for both treatment intervals thereby confirming the acceptable quality of the tissues.

Exposure to the positive control induced a decrease in the relative absorbance as compared to the negative control, both for the 3 minutes exposure period and for the 1 hour exposure period. The 1 hour exposure caused a decrease of the cell viability < 15% of the negative control. The CV in the range 20 – 100% viability between the tissue replicates is ≤ 30%, thus the validity of the test system and the specific batch of the tissue models is confirmed.

After exposure of the tissues to the test item the relative absorbance value was 86.83% after 3 minutes exposure. After 1 hour exposure the relative absorbance value was 70.83%. Both values did not reach the threshold for corrosivity which is defined to be < 50% after the 3 minutes exposure or ≥ 50% after 3 minutes exposure and < 15% after the 1 hour exposure. Therefore, the test item is considered to be not corrosive.

 

Conclusion

Under the conditions of the present study, the test item is not considered to possess a corrosive potential to skin.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Jun 20, 2020 - Aug 17, 2020

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)

Version / remarks:

Commission Regulation (EU) 2017/735 of 14 February 2017 amending, for the purpose of its adaption to technical progress, the Annex to Regulation (EC) No 440/2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH).

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

PREPARATION OF THE TEST MATERIAL
The test item was prepared as a 20% (w/v) suspension in a 0.9% sodium chloride solution. The stability in the vehicle was not investigated. The test item preparation was administered within <1 hour after preparation.

Vehicle:

physiological saline

Controls:

yes, concurrent vehicle

yes, concurrent positive control

Amount / concentration applied:

TEST MATERIAL: 750 µL (i.e. 150mg/750µL)

NEGATIVE / VEHICLE CONTROL: 750 µL

Designation: 0.9% sodium chloride solution
Supplier: B. Braun Melsungen AG, Germany
Batch: 16455011
Storage: 2 to 8°C
Released until: March 2021


POSITIVE CONTROL: 750 µL

Designation: Art. 814223
Synonym: Imidazole
Supplier: Merck KGaA, Germany
Batch: S5798623
Purity (GC) 99.8% (a/a)
Storage: At room temperature
Released until: April 30, 2023

Imidazole was dissolved with 0.9% sodium chloride solution to a concentration of 20% (w/v).

Duration of treatment / exposure:

240 minutes

Number of animals or in vitro replicates:

in vitro: triplicate design

Irritation parameter:

in vitro irritation score

Run / experiment:

Run 1 / Experiment 1

Value:

30.9

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

not determinable

Remarks:

According to OECD 437 no prediction can be made regarding the eye hazard potential of the test item.

Other effects / acceptance of results:

OTHER EFFECTS:
- Visible damage on test system: No observations (e.g. tissue peeling, residual test chemical, non-uniform opacity patterns) were seen in a visually inspection of the corneas after treatment.

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: After treatment with the negative control (0.9% sodium chloride solution) the calculated IVIS was 0.2 and, thus, within three standard deviations of the current historical mean of the negative control (IVIS: -1.4 – 3.1).
- Acceptance criteria met for positive control: After treatment with the positive control (20% Imidazole) the calculated IVIS was 103.8 and, thus, also within two standard deviations of the current historical mean of the positive control (IVIS: 83 – 131.8).

Therefore, the study fulfilled the acceptance criteria.

		Opacity	Permeability	IVIS
				per cornea	per group (mean value)	SD
Negative control	0.9% NaCl Solution	-0.2	0.012	-0.020	0.2	0.6
		-0.5	0.012	-0.320
		0.7	0.015	0.925
Positive control	20% Imidazole solution	74.2	2.639	113.785	103.8	8.8
		73.9	1.556	97.240
		70.8	1.966	100.290
Test item	Test item	31.7	-0.004	31.640	30.9	3.2
		27.4	-0.006	27.310
		33.7	-0.052	33.625

Interpretation of results:

other: Under the conditions of the present study, the eye hazard potential of the test item cannot be predicted.

Conclusions:

Under the conditions of the present study, the eye hazard potential of the test item cannot be predicted.

Executive summary:

Objective

The objective of the present study was to examine the potential of the test item to induce serious eye damage in the BCOP assay. The BCOP assay with isolated fresh bovine corneas is an accepted in vitro model for ocular hazard assessment.

 

Study Design

To determine the eye hazard potential the induced opacity and increased permeability was investigated in isolated bovine corneas after exposure to the test item as a 20% (w/v) suspension in a 0.9% sodium chloride solution. As negative control 0.9% sodium chloride solution and as positive control 20% (w/v) Imidazole was used.

 

Three corneas were used per group (negative control, positive control or test item group).

 

After a first opacity measurement of the untreated bovine corneas, 750 µL of the suspended test item, positive or negative control were applied on the corneas and incubated for 240 minutes. After the incubation phase the test item, the positive, and the negative control were rinsed from the corneas and the opacity was measured again.

 

After the opacity measurements, the permeability of the corneas was determined by application of a fluorescein solution for 90 minutes. The amount of fluorescein solution that crossed the cornea was measured spectrophotometrically.

 

The opacity and permeability assessments were combined to determine an In Vitro Irritancy Score (IVIS).

 

Results

After treatment with the negative control (0.9% sodium chloride solution) the calculated IVIS was 0.2 and, thus, within three standard deviations of the current historical mean of the negative control (IVIS: -1.4 – 3.0). After treatment with the positive control (20% Imidazole) the calculated IVIS was 103.8 and, thus, also within two standard deviations of the current historical mean of the positive control (IVIS: 83.0 – 131.8). Therefore, the study fulfilled the acceptance criteria.

 

The IVIS obtained after treatment with the test item was 30.9 and, thus higher than 3 and lower than 55, i.e.according to OECD 437 no prediction can be made regarding the eye hazard potential of the test item.

 

Conclusion

Under the conditions of the present study, the eye hazard potential of the test item cannot be predicted.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Feb 25, 2020 - May 27, 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 492 (Reconstructed Human Cornea-like Epithelium (RhCE) Test Method for Identifying Chemicals Not Requiring Classification and Labelling for Eye Irritation or Serious Eye Damage)

Version / remarks:

July 28, 2015

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: DB-ALM Protocol No. 164: Ocular Irritation Assay for Chemicals using EpiOcular™ EIT,

Version / remarks:

September 14, 2015

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: EpiOcular Eye Irritation Test (OCL-200-EIT) for the prediction of acute ocular irritation of chemicals; For use with MatTek Corporation`s Reconstructed Human EpiOcular Model; MatTek Corporation

Version / remarks:

June 29, 2015

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: No pre-treatment, the test item was applied neat to the tissues.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent positive control

yes, concurrent negative control

Amount / concentration applied:

TEST MATERIAL: 50 mg per tissue

NEGATIVE / VEHICLE CONTROL: 50 µL per tissue

Sterile deionized water was used as negative control.


POSITIVE CONTROL: 50 µL per tissue

Designation: Art. 8.09711
Synonym: Methyl acetate
Supplier: Merck KGaA
CAS No.: 79-20-9
Batch No.: S7451611
Appearance: Liquid
Assay (GC, area%): 99.6 % (a/a)
Minimum shelf life: June 30, 2022
Storage conditions: Tightly closed, dark, at room temperature (15 – 25°C)

Duration of treatment / exposure:

6 hours

Number of animals or in vitro replicates:

in vitro: duplicate design

Irritation parameter:

other: Viability %

Run / experiment:

Run 1 / Experiment 1

Value:

1.6

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

positive indication of irritation

Remarks:

According to OECD 492 no prediction can be made regarding the eye irritating potential.

Other effects / acceptance of results:

OTHER EFFECTS:
- Visible damage on test system: No observations

ACCEPTANCE OF RESULTS:
1. The negative control OD is >0.8 and <2.5 (1.671 and 1.474).
2. The mean relative viability of the positive control is below 50% of the negative control viability (40.0%).
3. The difference of viability between the two relating tissues of a single chemical is <20% (values between 1.1% to 12.5%) in the same run (for positive and negative control tissues and tissues of single chemicals).

The study met all acceptance criteria

	Mean OD	Mean Viability
Negative Control	1.573	100.0 %
Positive Control	0.629	40.0 %
Test Item	0.025	1.6 %

Interpretation of results:

other: UN GHS Category 1 or Category 2

Conclusions:

Under the conditions of the present study, the test item did show an eye hazard potential. The test item is considered to be UN GHS Category 1 or Category 2.

Executive summary:

Objective

The objective of the present study was to investigate the potential of the test item to induce eye irritation in an in vitro human cornea model.

 

Study Design

The test item was applied topically to a reconstructed human cornea-like epithelium model (EpiOcular) followed by determination of the cell viability. Cell viability was determined by enzymatic conversion of vital dye MTT into a blue formazan salt and measurement of the formazan salt after extraction from tissues. The percent reduction of cell viability in comparison to untreated negative controls was used to predict the eye irritation potential. Duplicates of the EpiOcular-model were treated with the test item, the negative or the positive control for 6 hours (± 15 minutes). 50 mg of the test item and 50 µL of either the negative control (sterile deionized water) or the positive control (methyl acetate) were applied to the tissues.

 

Results

After treatment with the negative control (sterile deionized water) the mean OD was 1.573 (study acceptance criterion: >0.8 and <2.5). Treatment with the positive control (methyl acetate) revealed a mean viability value of 40.0 % (study acceptance criterion: < 50 %). Thus, the acceptance criteria were met.

 

Following treatment with the test item, the tissue viability was 1.6 % and, thus, lower than 60%, i.e.according to OECD 492 the test item is considered to be UN GHS Category 1 or Category 2.

 

Conclusion

Under the conditions of the present study, the test item did show an eye hazard potential. The test item is considered to be UN GHS Category 1 or Category 2.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Justification for classification or non-classification

Based on the provided information the test item must be classified for skin irritation Category 2, as worst case assumption for eye corrosion Category 1 and respiratory tract irritation STOT SE 3 according to the EU Regulation (EC) No 1272/2008 on Classification, Labelling and Packaging of Substances and Mixtures.