Formamide, N-[(2-bromo-5-hydroxy-4-methoxyphenyl)methyl]-N-[2-(4-hydroxyphenyl)ethyl]-

Endpoint summary

Description of key information

Skin irritation:

In a K2 in vivo skin irritation study in New Zealand Whtie Rabbits according to OECD Guideline 404 and EU Method B.4 (Sanders, 2005), T002078 was observed to be non irritating to the skin. No classification is required for skin irritation or skin corrosion based on the criteria of the CLP regulation (EC) No 1272/2008.

Eye Irritation:

In a K1 Bovine Corneal Opacity and Permeability (BCOP) test, performed according to OECD guideline 437 (Westerink, 2017) T002078 did not induce occular irritation. No classification is required for eye irritation or serious eye damage based on the criteria of the CLP regulation (EC) No 1272/2008.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2005-11-22 to 2005-11-25

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Study according to OECD Guideline 404 (Acute Dermal Irritation / Corrosion) and EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion); limited information on test material and test system

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

no

Remarks:

The study was conducted in a facility operating to Good Laboratory Practice within the UK national GLP monitoring programme, but the study report has not been audited by the QA unit. No formal claim of GLP compliance is made for this study.

Specific details on test material used for the study:

no data

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS: no data

ENVIRONMENTAL CONDITIONS: no data

IN-LIFE DATES: no data

Type of coverage:

semiocclusive

Preparation of test site:

not specified

Remarks:

intact skin

Vehicle:

not specified

Controls:

other: Untreated skin areas were used as control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

up to 72 hours

Number of animals:

three

Details on study design:

TEST SITE: no data

REMOVAL OF TEST SUBSTANCE: no data

OBSERVATION TIM POINTS:
- Skin reactions were recorded at 1, 24, 48 and 72 hours after administration

SCORING SYSTEM:
- Primary Irritation Index, scoring based on observations of Erythema/Eschar formation and Oedema formation. [scoring index: 0= non-irritant, >0-2= mild irritant, >2-5= moderate irritant, >5-8= severe irritant]

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 and 72 hour readings

Score:

0.5

Max. score:

8

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animals number 19, 21, 22

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

edema score

Basis:

mean

Remarks:

animals number 19, 21, 22

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable - score 0

Irritant / corrosive response data:

- Very slight erythema was noted at two treated skin sites one hour after patch removal and at all treated skin sites at the 24-hour observation. All treated skin sites appeared normal at the 48-hour observation.

Skin Reaction	Observation Time	Individual Scores – Rabbit Number and Sex			Total
		19 Male	21 Male	22 Male
Erythema/Eschar Formation	1 Hour	0	1	1	(2)
	24 Hour	1	1	1	3
	48 Hour	0	0	0	(0)
	72 Hour	0	0	0	0
Oedema Formation	1 Hour	0	0	0	(0)
	24 Hour	0	0	0	0
	48 Hour	0	0	0	(0)
	72 Hour	0	0	0	0
Sum of 24 and 72 Hour Readings					3
Primary Irritation Index (S/6) and Classification					3/6=0.5
					Mild Irritant

( ) = Total values not used for calculation of primary irritation index

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the Primary Irritation Index (PII) was 0.5, indicating that the test substance is a mild irritant. Based on the mean scores for erythema and edema at 24, 48 and 72 hours of the 3 animals and the criteria of the CLP Regulation, the substance is considered as non irritant to the skin.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not 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:

supporting study

Study period:

2005-10-25

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Only a study summary was available for review which provided limited details on the test substance and methodology; however, sufficient information was provided to deem the study reliable with restrictions.

Qualifier:

according to guideline

Guideline:

other: SPL Standard Test Method 569.05

Deviations:

not specified

Principles of method if other than guideline:

The ocular irritancy potential of the test material was assessed using the rabbit enucleated eye test (REET). This method involved the application of the test material onto the cornea of the enucleated eye.

GLP compliance:

no

Remarks:

The study was conducted in a facility operating to Good Laboratory Practice within the UK national GLP monitoring programme, but the study report had not been audited by the QA Unit. No formal claim of GLP compliance was made for the study.

Specific details on test material used for the study:

no data

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

SOURCE OF COLLECTED EYES
- Source: New Zealand White rabbits
- Number of animals: 5
- Characteristics of donor animals (e.g. age, sex, weight): no data
- Storage, temperature and transport conditions of ocular tissue (e.g. transport time, transport media and temperature, and other conditions): the eyes were
maintained at a temperature of 32°C ± 1.5°C within the superfusion apparatus
- Time interval prior to initiating testing: no data
- indication of any existing defects or lesions in ocular tissue samples: no data
- Indication of any antibiotics used: no data

Vehicle:

not specified

Controls:

yes, concurrent negative control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL (which was found to be 57 mg)
- Concentration (if solution): no data

NEGATIVE CONTROL
- Amount(s) applied (volume or weight with unit): no data
- Concentration (if solution): 0.9%

Duration of treatment / exposure:

single application

Number of animals or in vitro replicates:

3 enucleated eyes were treated with the test item, 2 with enucleated eyes were treated as control

Details on study design:

REMOVAL OF TEST SUBSTANCE:
- washing: no

OBSERVATION TIME POINTS:
- corneal opacity and corneal epithelium condition: 60, 120, 180 and 240 min
- fluorescein uptake: 240 min
- corneal swelling: 60, 120 and 240 min

SCORING SYSTEM:
- No data

TOOL USED TO ASSESS SCORE:
- No data

Irritation parameter:

cornea opacity score

Remarks:

mean of 3 eyes

Run / experiment:

1

Value:

0

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not applicable

Remarks on result:

no indication of irritation

Remarks:

all scores were 0

Irritation parameter:

fluorescein retention score

Remarks:

mean of 3 eyes

Run / experiment:

1

Value:

0

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not applicable

Remarks on result:

other:

Remarks:

all scores were 0

Irritation parameter:

percent corneal swelling

Remarks:

mean of 3 eyes 60 min post dosing

Run / experiment:

1

Value:

3.6

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not applicable

Irritation parameter:

percent corneal swelling

Remarks:

mean of 3 eyes 120 min post dosing

Run / experiment:

1

Value:

2.7

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not applicable

Irritation parameter:

percent corneal swelling

Remarks:

mean of 3 eyes 240 min post dosing

Run / experiment:

1

Value:

0.6

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

not applicable

Other effects / acceptance of results:

negative control eyes:
- corneal opacity: 0 (mean of 2 eyes)
- corneal epithelium condition: normal (2 eyes)
- fluorescein uptake: 0 (mean of 2 eyes)
- corneal swelling: 2.8 at 60 min post dosing, 0.1 at 120 minutes post dosing and 0.0 at 240 minutes post dosing

Corneal epithelium condition was normal at all timepoints for all treated eyes.

Interpretation of results:

GHS criteria not met

Conclusions:

The test material is considered unlikely to have the potential to cause severe ocular irritancy in vivo.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-11-14 to 2016-12-13

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Well documented GLP study according to OECD guideline 437.

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)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: I15EB1917
- Expiration date of the lot/batch: 2017-09-07
- Purity test date: no data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature
- Stability under test conditions: no data
- Solubility and stability of the test substance in the solvent/vehicle: since no workable suspension of the test item in physiological saline could be obtained, the test item was used as delivered by the sponsor and added pure on top of the corneas.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: none, the test item was applied undiluted

Species:

other: bovine eyes

Strain:

other: not applicable

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: bovine eyes from young cattle were obtained from the slaughterhouse (Vitelco, -'s Hert ogenbosch, The Netherlands), where the eyes were excised by a slaughterhouse employee as s oon as possible after slaughter. Bovine eyes were used as soon as possible but within 4 hours after slaughter. Eyes were collected and transported in physiological saline in a suitable container under cooled conditions and tested the day of arrival in the laboratory.

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): 313.3 to 397.5 mg

NEGATIVE CONTROL
- Amount(s) applied (volume or weight with unit): 750 µL

POSITIVE CONTROL
- Amount(s) applied (volume or weight with unit): 750 µL
- Concentration (if solution): 20% Imidazole

Duration of treatment / exposure:

Corneas were incubated for 240 ± 10 minutes at 32 ± 1°C

Duration of post- treatment incubation (in vitro):

After 240 +/- 10 minutes minutes of treatment, opacity was measured with an opacitometer. The permeability measurement of the corneas was performed following the opacity measurement after an incubation period of 90 minutes ± 5 minutes.

Number of animals or in vitro replicates:

Three corneas were selected at random for each treatment group.

Details on study design:

SELECTION AND PREPARATION OF CORNEAS:
The eyes were checked for unacceptable defects, such as opacity, scratches, pigmentation and neovascularization by removing them from the physiological saline and holding them in the light. Those exhibiting defects were discarded.
The isolated corneas were stored in a petri dish with cMEM (Eagle’s Minimum Essential Medium (Life Technologies, Bleiswijk, The Netherlands) containing 1% (v/v) L-glutamine (Life Technologies) and 1% (v/v) Foetal Bovine Serum (Life Technologies)). The isolated corneas were mounted in a corneal h older (one cornea per holder) of BASF (Ludwigshafen, Germany) with the endothelial side against the O-ring of the posterior half of the holder. The anterior half of the holder was positioned on top of the cornea and tightened with screws. The compartments of the corneal holder were filled with cMEM of 32 ± 1°C. The corneas were incubated for the minimum of 1 hour at 32 ± 1°C.
After the incubation period, the medium was removed from both compartments and replaced with fre sh cMEM.

TREATMENT METHOD:
The medium from the anterior compartment was removed and 750 µL of the negative control amd positive control were introduced onto the epithelium of the cornea. The test item was weighed in a bottle and applied directly on the corneas in such a way that the cornea was completely covered (313.3 to 397.5 mg). The holder was slightly rotated, with the corneas maintained in a horizontal position, to ensure uniform distribution of the solutions over the entire cornea. Corneas were incubated in a horizontal position for 240 ± 10 minutes at 32 ± 1°C.

REMOVAL OF TEST SUBSTANCE:
- Number of washing steps after exposure period: After the incubation the solutions and the test item were removed and the epithelium was washed at least three times with MEM with phenol red (Eagle’s Minimum Essential Medium Life Technologies). Possible pH effects of the test item on the corneas were recorded. Each cornea was inspected visually for dissimilar opacity pat terns. The medium in the posterior compartment was removed and both compartments were refilled with fresh cMEM and the opacity determinations were performed.

METHODS FOR MEASURED ENDPOINTS:
- CORNEAL OPACITY: Opacity determinations were performed on each of the corneas using an opacitometer (BASF-OP3.0, BASF, Ludwigshafen, Germany). The opacity of each cornea will be read against a cMEM filled chamber, and the initial opacity reading thus determined will be recorded. Corneas that had an initial opacity reading higher than 7 were not used.
The opacity of a cornea was measured by the diminution of light passing through the cornea. The light was measured as illuminance (l = luminous flux per area, unit: lux) by a light meter. The opacity value (measured with the device OP-KIT) was calculated according to: opacity = ((I0/I)-0.9894)/0.0251
With I0 the empirically determined illuminance through a cornea holder but with windows and medium, and I the measured illuminance through a holder with cornea before/after test item treatment. The change of opacity for each individual cornea (including the negative control) was calculated by subtracting the initial opacity reading from the final post-treatment reading. The corrected opacity for each positive control or test item treated cornea was calculated by subtracting the average change in opacity of the negative control corneas from the change in opacity of each positive control or test item treated cornea. The mean opacity value of each treatment group was calculated by averaging the corrected opacity values of the treated corneas for each treatment group.

- CORNEAL PERMEABILITY: passage of sodium fluorescein dye measured with the aid of microtiter plate reader (OD490)
The medium of both compartments (anterior compartment first) was removed. The posterior compa rtment was refilled with fresh cMEM. The anterior compartment was filled with 1 mL of 5 mg Nafluorescein/mL cMEM solution (Sigma-Aldrich Chemie GmbH, Germany). The holders were slightly rotated, with the corneas maintained in a horizontal position, to ensure uniform distribution of the sodium-fluorescein solution over the entire cornea. Corneas were incubated in a horizontal position for 90 ± 5 minutes at 32 ± 1°C.
After the incubation period, the medium in the posterior compartment of each holder was removed and placed into a sampling tube labelled according to holder number. 360 μL of the medium from each sampling tube was transferred to a 96-well plate. The optical density at 490 nm (OD490) of each sampling tube was measured in triplicate using a microplate reader (TECAN Infinite® M200 Pro Plate Reader). Any OD490 that was 1.500 or higher was diluted to bring the OD490 into the acceptable ra nge (linearity up to OD490 of 1.500 was verified before the start of the experiment). OD490 values of less than 1.500 were used in the permeability calculation.

The mean OD490 for each treatment was calculated using cMEM corrected OD490 values. If a dilution was performed, the OD490 of each reading was corrected for the mean negative control OD490 before the dilution factor was applied to the readings.

SCORING SYSTEM: In Vitro Irritancy Score (IVIS) The mean opacity and mean permeability values (OD490) were used for each treatment group to c alculate an in vitro score: In vitro irritancy score (IVIS) = mean opacity value + (15 x mean OD490 value) Additionally the opacity and permeability values were evaluated independently to determine whether the test item induced irritation through only one of the two endpoints.
The IVIS cut-off values for identifying the test items as inducing serious eye damage (UN GHS Category 1) and test items not requiring classification for eye irritation or serious eye damage (UN GHS No Category) are given hereafter:
In vitro score range UN GHS
≤ 3 No Category
> 3; ≤ 55 No prediction can be made
>55 Category 1

Irritation parameter:

in vitro irritation score

Remarks:

mean

Run / experiment:

Test item after 240 minutes of exposure-1st test

Value:

4.8

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other:

Remarks:

range of IVIS score of test item 1.2 to 7.5

Irritation parameter:

cornea opacity score

Remarks:

mean

Run / experiment:

Test item after 240 minutes of exposure-1st test

Value:

3.3

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other:

Remarks:

Range of corneal opacity score of test item 0.5 to 6.1

Irritation parameter:

other: permeability value mean

Run / experiment:

Test item after 240 minutes of exposure-1st test

Value:

0.102

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other:

Remarks:

Range of permeability value of test item 0.049 to 0.163

Irritation parameter:

in vitro irritation score

Remarks:

mean

Run / experiment:

Test item after 240 minutes of exposure-2nd test

Value:

0.5

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other:

Remarks:

Range of IVIS score of test item -1.1 to 1.5

Irritation parameter:

cornea opacity score

Remarks:

mean

Run / experiment:

st item after 240 minutes of exposure-2nd test

Value:

-0.2

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other:

Remarks:

Range of corneal opacity score of test item -1.3 to 0.6

Irritation parameter:

other: permeability value

Remarks:

mean

Run / experiment:

Test item after 240 minutes of exposure-2nd test

Value:

0.051

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other:

Remarks:

Range of permeability value of test item 0.013 to 0.081

Other effects / acceptance of results:

1st Test
mean in vitro irritancy score (range):
negative control: 1.8 (1.2 to 2.6)
positive control: 149.1 (123.3 to 199.6)

mean opacity scores (range):
negative control: 1.5 (1.0 to to 2.3)
positive control: 120.6 (96.4 to 158.8)

mean permeability scores (range):
negative control: 0.018 (0.012 to 0.022)
positive control: 1.897 (1.107 to 2.717)

Other effects:
The corneas treated with the positive control were turbid with spots after the 240 minutes of treatment. All corneas were translucent with spots after the 240 minutes of treatment with the test item. No pH effect of the test item was observed on the rinsing medium.

Interpretation: Since the IVIS scores were spread over two categories, the experiment was repeated.

2nd Test
mean in vitro irritancy score (range):
negative control: 2.4 (2.1 to 2.8)
positive control: 159.7 (142.7 to 184.0)

mean opacity scores (range):
negative control: 1.8 (1.3 to 2.4)
positive control: 135.9 (121.9 to 162.9)

mean permeability scores (range):
negative control: 0.037 (0.027 to 0.053)
positive control: 1.588 (1.330 to 2.024)

Other effects:
The corneas treated with the positive control were turbid with spots after the 240 minutes of treatment. All corneas were slightly translucent after the 240 minutes of treatment with the test item. No pH effect of the test item was observed on the rinsing medium.

Interpretation:
Over two experiments, the test item did not induce ocular irritation through both endpoints with an IVIS <3 in 4 out of 6 eyes, resulting in a mean in vitro irritancy score of 2.7 (-1.1 to 7.5) after 240 minutes of treatment.Since the test item induced an IVIS ≤ 3, no classification is required for eye irritation or serious eye damage.

Acceptance of results:
The negative control responses for opacity and permeability were less than the upper limits of the laboratory historical range indicating that the negative control did not induce irritancy on the corneas . The mean in vitro irritancy score of the positive control (20% (w/v) Imidazole) were 149.1 and 159.7 (123.3 to 199.6 and 142.7 to 184.0) ) and was within the current historical positive control data range. The opacity for one of the positive control eyes was just above the historical mean + 2 SD in the second experiment. Since the mean opacity of the positive control eyes in the second experiment is lower than the historical mean +2 SD, this does not affect study outcome. It was therefore concluded that the test conditions were adequate and that the test system functioned properly.

Interpretation of results:

GHS criteria not met

Conclusions:

Since the test item induced an IVIS ≤ 3, no classification is required for eye irritation or serious eye damage.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation / corrosion:

Sanders (2005) investigated acute dermal irritation of T002078 in 3 male New Zealand White rabbits (semi-occlusive patch) after 4 hours of exposure to 0.5 g of test item. Skin reactions were recorded 1, 24, 48, and 72 hours after patch removal.

Very slight erythema was noted at two treated skin sites one hour after patch removal and at all treated skin sites at the 24-hour observation. All treated skin sites appeared normal at the 48-hour observation.

Based on the mean scores for erythema and edema at 24, 48 and 72 hours of the 3 animals and the criteria of the CLP Regulation (EC) No 1272/2008, the test item is considered as non irritant to the skin.

An in vitro skin irritation study was waived based on the justification that adequate data from an in vivo skin irritation study are available.

Eye irritation:

Westerink (2017) investigated eye irritation in an in vitro bovine corneal opacity-permeability (BCOP) assay. 313.3 to 397.5 mg of the test item was applied on the top of 3 corneas for 240 +/- 10 minutes. Both opacity and permeability were measured and the resulting objective values were combined in an empirically derived formula to generate an In Vitro Irritancy Score (IVIS). The corneas treated with T002078 were translucent with spots after the 240 minutes of treatment. The mean in vitro irritancy score was 4.8 (1.2 to 7.5), since the IVIS scores were spread over two categories, the experiment was repeated. The IVIS scores of the second test was 0.8 (-1.2 to 2.5) after 240 +/- 10 minutes.

Over two experiments, the test item did not induce ocular irritation through both endpoints with an IVI S <3 in 4 out of 6 eyes, resulting in a mean in vitro irritancy score of 2.7 (-1.1 to 7.5) after 240 minutes of treatment. Since the test item induced an IVIS ≤ 3, no classification is required for eye irritation or serious eye damage.

In addition, a rabbit enucleated eye test (REET) was performed by Sanders (2005) to assess the ocuar irritancy potential of T002078. Three enucleated eyes, obtained from the New Zealand White strain of rabbit, were treated with 0.1 mL (which was found to be 57 mg of T002078). Corneal opacity (60, 120, 180 and 240 minutes after application), corneal swelling (60, 120 and 240 minutes after application) and fluorescein uptake (240 minutes after application) were observed and scored. No indication of irritation was noted.

The test item was not considered to have the potential to cause severe occular irritancy in vivo.

The BCOP study is considered the key result for assessing the eye irritation endpoint. According to Chapter R.7a: Endpoint specific guidance Version 6.0 - July 2017 (R.7.2.11.2), data obtained from non-validated suitable in vitro tests can only be used according to the criteria set out in section 1.4 of Annex XI to the REACH Regulation, i.e. only positive results can be accepted in a weight of evidence approach. As the result of the non-validated REET test was negative, this study was added to the dossier as supporting evidence and the newly conducted and validated BCOP study is selected as key study for classification purposes.

Justification for classification or non-classification

Skin irritation:

According to the in vivo acute dermal irritation study, very slight erythema was noted at one hour and 24 hours after the test item was removed, but all sites were normal after 48 hours. Based on the results of this study and the criteria of the CLP Regulation (EC) No 1272/2008, the test item does not meet the criteria for classification as irritant or corrosive.

Eye irritation:

According to the in vitro eye irritation study (BCOP), T002078 induced no ocular irritation over two experiments, resulting in a mean in vitro irritancy score of 2.7. The test item did not meet the criteria for classification and no classification is required for eye irritation of serious eye damage according to the criteria of the CLP regulation (EC) No 1272/2008.