Registration Dossier

Administrative data

Description of key information

Skin irritation:

In a K2 in vivo skin irritation study in New Zealand White Rabbits equivalent to OECD Guideline 404 and EU Method B.4, T002488 was not irritating to the skin 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 and EU Method B.47, T002488 did not induce ocular irritation. No classification is required for eye irritation or serious eye damage according to the criteria of the CLP regulation (EC) No 1272/2008.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2004-11-04 to 2004-11-12
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Study is similar to OECD Guideline 404 (Acute Dermal Irritation / Corrosion) and EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion); however, the test substance is not adequately characterized and insufficient information is provided on the test animals.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
: Insufficient information on the test substance and test animals.
Qualifier:
equivalent or similar to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
: Insufficient information on the test substance and test animals.
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 and environmental conditions:
TEST ANIMALS:
- 3 male New Zealand White rabbits, no further data

ENVIRONMENTAL CONDITIONS: no data
Type of coverage:
semiocclusive
Preparation of test site:
other: intact
Vehicle:
not specified
Controls:
other: Untreated skin areas of the test animals served as control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution): no data
Duration of treatment / exposure:
Method 1: 4 hours
Method 2: 3 minutes and 1 hour
Observation period:
Method 1: 72 hours
Method 2: 72 hours
Number of animals:
Method 1: 3
Method 2: 1
Details on study design:
TEST SITE: no data

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
- Skin reactions were recorded 1, 24, 48 and 72 hours after administration.

SCORING SYSTEM:
- according to Draize
- Primary Irritation Index
0 = Non-irritant
>0 - 2 = Mild irritant
>2 - 5 = Moderate irritant
>5 - 8 = Severe irritant
Irritation parameter:
erythema score
Basis:
mean
Remarks:
following 4-hour exposure
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: A score of 0 was obtained for the three rabbits.
Irritation parameter:
edema score
Basis:
mean
Remarks:
following 4-hour exposure
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: A score of 0 was obtained for the three rabbits.
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
following 3-minute exposure
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not aplicable
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
following 3-minute exposure
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
following 1-hour exposure
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
No evidence of skin irritation was noted.
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was found to be a non-irritant with a primary irritation index of 0.0.
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

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
From 2004-10-28 to 2004-10-28
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
While only a study summary was available for review which provided limited details on the test substance and methodology, sufficient information was provided to deem the study reliable with restrictions.
Qualifier:
no guideline followed
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 rabbit, no further data
- Number of animals: no data
- 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 enucleated eyes were maintained at a temperature of 32°C +/- 1.5°C within the superfusion apparatus.
Vehicle:
not specified
Controls:
yes, concurrent negative control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL of the test material, which was found to weigh approximately 56 mg, was applied onto the cornea of each of three enucleated eyes.
- 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
Observation period (in vivo):
240 min
Number of animals or in vitro replicates:
3 enucleated eyes were treated with the test item and 2 enucleated eyes were treated with the control
Details on study design:
REMOVAL OF TEST SUBSTANCE: no data

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:
The direct effect of the test material on the cornea was assessed by evaluation of corneal thickness, corneal opacity, alteration of corneal epithelium and fluorescein uptake, throughout the duration of the study.


TOOL USED TO ASSESS SCORE:
no data
Irritation parameter:
cornea opacity score
Remarks:
mean of 3 eyes 60 and 120 min post dosing
Run / experiment:
1
Value:
0
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
not applicable
Irritation parameter:
cornea opacity score
Remarks:
mean of 3 eyes 180 and 240 min post dosing
Run / experiment:
1
Value:
1
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
not applicable
Irritation parameter:
percent corneal swelling
Remarks:
mean of 3 eyes 60 min post dosing
Run / experiment:
1
Value:
11.5
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:
10
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:
9.1
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
not applicable
Irritation parameter:
other: fluorescein uptake
Remarks:
mean of 3 eyes
Run / experiment:
1
Value:
0.67
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: 6.0 at 60 min post dosing, 1.9 at 120 minutes post dosing and 0.0 at 240 minutes post dosing

Corneal epithelium condition of test item treated eyes was normal at all timepoints.

Table 1. Results obtained for corneal opacity at 60, 120, 180, and 240 minutes post exposure.

 

Corneal Opacity

Observation Period (minutes post dosing)

60

120

180

240

Cldy

Area

Cldy

Area

Cldy

Area

Cldy

Area

Test Eyes

0

0

0

0

1

1

1

1

0

0

0

0

1

1

1

1

0

0

0

0

1

1

1

1

Control Eyes

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Cldy = Corneal opacity

 

 

Table 2. Results obtained for corneal epithelium condition at 60, 120, 180, and 240 minutes post exposure.

 

Corneal Epithelium Condition

Observation Period (minutes post dosing)

60

120

180

240

Test Eyes

Normal

Normal

Normal

Normal

Normal

Normal

Normal

Normal

Normal

Normal

Normal

Normal

Control Eyes

Normal

Normal

Normal

Normal

Normal

Normal

Normal

Normal

 

 

Table 3. Results obtained for fluorescein uptake 240 minutes post exposure.

 

Fluorescein Uptake (240 minutes)

Test Eyes

Control Eyes

Int

1

1

0

0

0

Area

1

1

0

0

0

Int = Intensity of fluorscein uptake

 

Table 4. Results obtained for corneal swelling at 60, 120, and 240 minutes post exposure.

 

Corneal Swelling (%)(minutes post dosing)

60

120

240

Test Eyes

11.5

10.0

9.1

Control Eyes

6.0

1.9

0.0

Test eyes results are the mean of three eyes while control eyes are the mean of two 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.
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 2015-11-16 to 2015-11-17
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Well documented GLP study according to OECD guideline 437 and EU method B.47.
Qualifier:
according to
Guideline:
OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
Deviations:
no
Qualifier:
according to
Guideline:
EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)
Deviations:
no
Principles of method if other than guideline:
The study procedures were also in compliance with the following guidelines:
- The Ocular Toxicity Working Group (OTWG) of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and the National Interagency Centre for the Evaluation of Alternative Toxicological Methods (NICEATM), Background Review Document (BRD): current status of in vitro test methods for identifying ocular corrosives and severe irritants: The Bovine Corneal Opacity and Permeability (BCOP) Test Method, March 2006.
- In Vitro Techniques in Toxicology Database (INVITTOX) protocol 127. Bovine Opacity and Permeability (BCOP) Assay, 2006.
- Gautheron P, Dukic M, Alix D and Sina J F, Bovine corneal opacity and permeability test: An in vitro assay of ocular irritancy. Fundam Appl Toxicol 18:442-449, 1992.
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
- Name of test material (as cited in study report): JNJ-4754724-AAA (T002488)
- Substance type: Light brown powder
- Physical state: solid
- Analytical purity: 102.2 % (HPLC determination with specification >=95%)
- Impurities (identity and concentrations): T002487 – RRT.55 < 0.01 % (w/w); total impurities <0.10 % (w/w)
- Purity test date: 1 July 2015
- Lot/batch No.: I15FC2164
- Expiration date of the lot/batch: 23 June 2017 (retest date)
- Storage condition of test material: At room temperature
Species:
other: bovine eyes
Strain:
other: not applicable
Details on test animals or tissues and environmental conditions:
TEST SYSTEM
- Source: bovine eyes from young cattle were obtained from the slaughterhouse (Vitelco, -'s Hertogenbosch, The Netherlands), where the eyes were excised by a slaughterhouse employee as soon 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.

- 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 holder (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.
Controls:
other: negative control (physiological saline) and positive control (20% (w/v) Imidazole solution in physiological saline)
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 305.9 to 346.2 mg
- 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.

POSITIVE CONTROL
- Amount applied: 750 µL
- Concentration (if solution): 20% (w/v) imidazole solution prepared in physiological saline

NEGATIVE CONTROL
- Amount(s) applied (volume or weight with unit): 750 µl
Duration of treatment / exposure:
Corneas were incubated for 240 ± 10 minutes at 32 ± 1°C
Observation period (in vivo):
After 240 ± 10 minutes of treatment, opacity was measured with an opacitometer. The permeability measurement of the corneas was performed after the incubation period of 90 minutes ± 5 minutes following the opacity measurement.
Number of animals or in vitro replicates:
Three corneas were selected at random for each treatment group
Details on study design:
CORNEA SELECTION AND OPACITY READING
After the incubation period, the medium was removed from both compartments and replaced with fresh cMEM. Opacity determinations were performed on each of the corneas using an opacitometer (BASF-OP3.0, BASF, Ludwigshafen, Germany). The opacity of each cornea was read against an air filled chamber, and the initial opacity reading thus determined was recorded. Corneas that had an initial opacity reading higher than 7 were not used. Three corneas were selected at random for each treatment group.

TREATMENT OF CORNEAS AND OPACITY MEASUREMENTS
The medium from the anterior compartment was removed and 750 µL of the negative control and 20% (W/v) Imidazole solution (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. 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. After the incubation the solutions and the test compound 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 patterns. The medium in the posterior compartment was removed and both compartments were refilled with fresh cMEM and the opacity determinations were performed.

OPACITY MEASUREMENT
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.

APPLICATION OF SODIUM FLUORESCEIN
Following the final opacity measurement, permeability of the cornea to Na-fluorescein (Merck) was evaluated.

The medium of both compartments (anterior compartment first) was removed. The posterior compartment was refilled with fresh cMEM. The anterior compartment was filled with 1 mL of 5 mg Na-fluorescein/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.

PERMEABILITY DETERMINATIONS
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 range (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.

ELECTRONIC DATA CAPTURE
Observations/measurements in the study were recorded electronically using the following programme: Magellan Tracker 7.0 (TECAN, Austria) for optical density measurement.

INTERPRETATION
The mean opacity and mean permeability values (OD490) were used for each treatment group to calculate 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
Value:
-0.4
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: range: -0.9 to 0.4
Irritation parameter:
cornea opacity score
Value:
-0.5
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: range: -1.0 to 0.3
Irritation parameter:
other: permeability score
Value:
0.005
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: range: 0.003 to 0.007
Other effects / acceptance of results:
mean in vitro irritancy score (range):
negative control: 0.2 (from - 0.6 to 1.4)
positive control:136.9 (from 115.1 to 178.4)
test item: -0.4 (from -0.9 to 0.4)

mean opacity scores (range):
negative control: 0.1 (from -0.6 to 1.3)
positive control: 109.4 (from 85.8 to 148.1)
test item: -0.5 (from -1.0 to 0.3)

mean permeability scores (range):
negative control: 0.004 (from -0.002 to 0.007)
positive control: 1.834 (from 1.395 to 2.089)
test item: 0.005 (from 0.003 to 0.007)

The corneas treated with the positive control were turbid after the 240 minutes of treatment.
The corneas treated with the test item were clear after the 240 minutes of treatment. No pH effect of the test item was observed on the rinsing medium.

Interpretation:

The IVIS of all replicates was within one category.

Discussion:

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) was 136.9 (115.1 to 178.4) and within the historical positive control data range. Furthermore the opacity and permeability values of the positive control were within two standard deviations of the current historical mean. It was therefore concluded that the test conditions were adequate and that the test system functioned properly.

The test item did not induce ocular irritation through both endpoints, resulting in a mean in vitro irritancy score of -0.4 (-0.9 to 0.4) after 240 minutes of treatment.

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

Interpretation of results:
GHS criteria not met
Conclusions:
The test item did not induce ocular irritation through both endpoints, resulting in a mean in vitro irritancy score of -0.4 (-0.9 to 0.4) after 240 minutes of treatment. 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:

Sanders (2004) investigated acute dermal irritation of T002488 in 3 male New Zealand White rabbits after 4 hours (Method 1), 3 minutes and 1 hour (Method 2) of exposure to 0.5 mg of test item. Skin reactions for both methods were recorded 1, 24, 48, and 72 hours after administration. Under the conditions of this study, no evidence of skin irritation was noted. Based on the results of this study, the test item does not meet the criteria for classification as irritant or corrosive according to the criteria of the CLP regulation (EC) No 1272/2008.

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:

Eurlings (2016) investigated eye irritation in an in vitro bovine corneal opacity-permeability (BCOP) assay according to OECD Guideline 437 and EU Method B.47. 305.9 to 346.2 mg of test item was applied pure on the top of 3 corneas for 240 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 T002488 were clear after the 240 minutes of treatment. The test item did not induce ocular irritation through both endpoints, resulting in a mean in vitro irritancy score of -0.4 (-0.9 to 0.4) after 240 minutes. 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 (2004) to assess the ocular irritancy potential of T002488. Three enucleated eyes, obtained from the New Zealand White strain of rabbit, were treated with 0.1 mL of test item (which weighed approximately 56 mg) of T002488. 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 ocular 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 5.0 - December 2016 (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, no skin irritation was noted for T002488. The test item did not meet the criteria for classification as irritant or corrosive according to the criteria of the CLP regulation (EC) No 1272/2008.

Eye irritation:

According to the in vitro eye irritation study (BCOP), T002488 induced no ocular irritation. No classification is required for eye irritation or serious eye damage according to the criteria of the CLP regulation (EC) No 1272/2008.