Registration Dossier

Administrative data

Description of key information

Skin irritation

In a key acute dermal irritation/corrosion study in New Zealand White rabbits similar to OECD Guideline 404, no evidence for skin irritation was noted for T000625 and the substance is not classified according to criteria in the CLP regulation (Sanders, 2004).

Eye irritation

In a key, in vitro eye irritation study performed according to OECD Guideline 437 and the criteria of the CLP Regulation (EC) No 1272/2008, no classification is required for eye irritation or serious eye damage (Eurlings, 2016).

 

Based on the results of Rabbit Enucleated Eye Test (REET), the test material was considered unlikely to have the potential to cause severe ocular irritancy in vivo.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Non GLP and provided limited information on materials and methods. However, the report stated that the methods in the study followed OECD guideline 404.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
limited information on test item and test system
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 complicance 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 test system and environmental conditions:
No data
Type of coverage:
semiocclusive
Preparation of test site:
not specified
Vehicle:
not specified
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
Skin reactions were recorded 1, 24, 48 and 72 hours after administration.
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: No data
- % coverage: No data
- Type of wrap if used: No data


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


SCORING SYSTEM: Classification categories for irritant were from Draize J H (1995) "Dermal Toxicity" in Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Assoc. of Food and Drug Officials of the US, Austin, Texas p47. Classification was based on the Primary Irritation Index (calculated from erythema/eschar formation and oedema formation scores) from the 24 and 72 hour time points.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: Based on 24 and 72 hour time points
Score:
ca. 0
Max. score:
6
Remarks on result:
other: All three animals scored a 0 for erythema/eschar formation and oedema formation at all time points evaluated.
Irritation parameter:
erythema score
Basis:
mean
Remarks:
3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
No evidence of skin irritation (erythema/eschar formation and oedema formation) was noted at any of the time points evaluated (1, 24, 48 and 72 hours).
Interpretation of results:
GHS criteria not met
Conclusions:
The test item was determined to be a non-irritant, based on a primary index score of 0.0. Based on the criteria of the CLP regulation (EC) 1272/2008, the test item did not meet the criteria for classification.
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:
key study
Study period:
From 2016-05-30 to 2016-06-14
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
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
Qualifier:
according to guideline
Guideline:
EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)
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: 16AB0081
- Expiration date of the lot/batch: 2018-01-11 (retest date)
- 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

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: none, the test item was added pure on top of the corneas.
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 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.

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent positive control
yes, concurrent negative control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 330 to 397 mg

NEGATIVE CONTROL
- Amount applied: 750 µL

POSITIVE CONTROL
- Amount applied: 750 µL
- Concentration: 20% (w/v) imidazole solution
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 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:
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 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.
After the incubation period, the medium was removed from both compartments and replaced with fresh cMEM.

TREATMENT METHOD:
The medium from the anterior compartment was removed and 750 µL of either the negative control, positive control (20% (w/v) Imidazole solution) or 20% (w/v) test item was 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.

REMOVAL OF TEST SUBSTANCE
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.

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 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.
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 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.
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.

SCORING SYSTEM: In Vitro Irritancy Score (IVIS)
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
Remarks:
mean of 3 eyes
Run / experiment:
1
Value:
0.4
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Remarks:
IVIS score range of test substance: -1.5 to 2.3
Irritation parameter:
cornea opacity score
Remarks:
mean of 3 eyes
Run / experiment:
1
Value:
0.4
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: range of corneal opacity score of test substance: -1.3 to 2.4
Irritation parameter:
other: permeability value
Remarks:
mean of 3 eyes
Run / experiment:
1
Value:
0.002
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: range of permeability value of test substance: -0.011 to 0.026
Irritation parameter:
in vitro irritation score
Remarks:
mean of 3 eyes
Run / experiment:
2
Value:
-2.1
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Remarks:
IVIS range of test substance: -4.0 to -0.6
Irritation parameter:
cornea opacity score
Remarks:
mean of 3 eyes
Run / experiment:
2
Value:
-2.2
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: range of corneal opacity score of test substance: -3.9 to -0.9
Irritation parameter:
other: permeability value
Remarks:
mean of 3 eyes
Run / experiment:
2
Value:
0.006
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: range of permeability value: -0.002 to 0.020
Other effects / acceptance of results:
FIRST TEST
mean in vitro irritancy score (range):
negative control: 1.2 (1.0 to 1.5)
positive control: 117.6 (107.6 to 132.0)

mean opacity scores (range):
negative control: 0.9 (0.7 to 1.2)
positive control: 101.6 (93.2 to 116.9)

mean permeability scores (range):
negative control: 0.019 (0.017 to 0.021)
positive control: 1.063 (0.960 to 1.224)

REPEAT TEST
mean in vitro irritancy score (range):
negative control: 0.2 (-3.3 to 2.5)
positive control: 104.7 (99.1 to 115.8)

mean opacity scores (range):
negative control: 0.1 (-3.4 to 2.5)
positive control: 78.9 (64.0 to 101.2)

mean permeability scores (range):
negative control: 0.005 (0.000 to 0.008)
positive control: 1.717 (0.974 to 2.337)

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

The IVIS of all replicates was within one category.

The test was accidently repeated however not needed since the IVIS scores of the eyes treated with test item were within the same category. 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.

In the first test, 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. One of the corneas treated with the negative control was excluded due to spots observed after the treatment. The mean in vitro irritancy score of the positive control (20% (w/v) Imidazole) was 118 (108 to 132) 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.

In the repeat test, 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 was 105 (99 to 116) 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.
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 (-1.5 to 2.3) and -2.1 (-4.0 to -0.6) (first and repeat test, respectively) 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:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2004-02-23
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:
no guideline available
Principles of method if other than guideline:
The ocular irritancy potential of the test material was assessed using the Rabbit Enucleated Eye Test (REET).
GLP compliance:
no
Remarks:
The study was conducted in a facility operating to GLP, but the study report has not been audited by the QA unit. No formal claim of GLP compliance is made.
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:
TEST SYSTEM
- five enucleated eyes, obtained from the New zealand White strain of rabbit

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 32+/- 1.5°C within the superfusion apparatus
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent negative control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL = approx. 85 mg, applied onto the cornea of each of three enucleated eyes.

NEGATIVE CONTROL
- Amont applied: 0.1 mL
Duration of treatment / exposure:
4 hours
Observation period (in vivo):
1, 2, 3 and 4 hours after dosing
Number of animals or in vitro replicates:
Test substance was tested on 3 eyes.
Two enucleated eyes were treated for control purposes with saline solution
Details on study design:
REMOVAL OF TEST SUBSTANCE: no data

SCORING SYSTEM: McDonald-Shadduck Score System

CORNEA:
- The direct effect of the test material on the cornea was assessed by evalution of corneal thikness, corneal opacity, alteration of corneal epithelium and fluorescein uptake, throughout the duration of the study. The data for all endpoints was assessed and an estimate of the ocular irritancy potential made.
- The scoring scheme measures the severity of corneal cloudiness and the area of the cornea involved.

Severity of corneal cloudiness is graded as follows:
0 = Normal cornea. Appears with the slit-lamp as having a bright grey line on the epithelial surface and a bright grey appearance of the stroma.
1 = Some loss of transparency. Only the anterior half of the stroma is involved as observed with an optical section of the slit-lamp. The underlying structures are clearly visible with diffuse illumination, although some cloudiness can be readily apparent with diffuse illumination.
2= Moderate loss of transparency. In addition to involving the anterior stroma, the cloudiness extends all the way to the endothelium. The stroma has lost its marble-like appearance and is homogeneously white. With diffuse, illumination, underlying structures are clearly visible.
3 = Involvement of the entire thickness of the stroma. With optical section, the endothelial surface is still visible. However, with diffuse illumination the underlying structures are just visible.
4 = Involvement of the entire thickness of the stroma. With the optical section cannot clearly visualise the endothelium. With diffuse illumination, the underlying structures cannot be seen.

The surface of the cornea relative to the area of cloudiness is divided into five grades from 0 to 4:
0 = Normal cornea with no area of cloudiness
1 = 1 to 25% area of stromal cloudiness
2 = 26 to 50% area of stromal cloudiness
3 = 51 to 75% area of stromal cloudiness
4 = 76 to 100% area of stromal cloudiness

FLUORESCEIN
- The use of fluorescein is a valuable aid in defining epithelial damage for fluorescein staining. The area can be judged as a 0 to 4 scale using the same terminology as for corneal cloudiness. The intensity of fluorescein staining can be divided into a 0 to 4 scale.
0 = Absence of fluorescein staining
1 = Slight fluorescein staining confined to a small focus. With diffuse illumination the underlying structures are clearly visible, although there is some loss of detail.
2 = Moderate fluorescein staining confined to a small focus. With diffuse illumination the underlying structures are clearly visible, although there is some loss of detail.
3 = Marked fluorescein staining. Staining may involve a larger portion of the cornea. With diffuse illumination underlying structures are barely visible but are not completely obliterated.
4 = Extreme fluorescein staining. With diffuse illumination the underlying structures cannot be seen.

TOOL USED TO ASSESS SCORE: hand-slit lamp, biomicroscope and fluorescein dye
Irritation parameter:
cornea opacity score
Remarks:
mean of 3 eyes, 60, 120, 180 and 240 min post dosing
Run / experiment:
1
Value:
0
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
not applicable
Irritation parameter:
other: fluorescein uptake
Remarks:
mean of 3 eyes, 240 min post dosing
Run / experiment:
1
Value:
0
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
not applicable
Irritation parameter:
percent corneal swelling
Remarks:
60 min post dosing
Run / experiment:
1
Value:
7.6
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
not applicable
Irritation parameter:
percent corneal swelling
Remarks:
120 min post dosing
Run / experiment:
1
Value:
8.3
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
not applicable
Irritation parameter:
percent corneal swelling
Remarks:
240 min post dosing
Run / experiment:
1
Value:
7.9
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
not applicable
Other effects / acceptance of results:
negative control results:
- corneal opacity: 0 (60, 120, 180 and 240 min post dosing, mean of 2 eyes)
- corneal eptithelium condition: noram at all timepoints (60, 120, 180 and 240 min post dosing, 2 eyes)
- fluorescein uptake: 0 (240 min post dosing, mean of 2 eyes)
- corneal swelling (%): 5.3 at 60 min post dosing, 3.0 at 120 min post dosing, 2.5 at 240 min post dosing

Corneal epithelium condition was normal at all timepoints for all test item treated eyes.
Interpretation of results:
GHS criteria not met
Conclusions:
Following assessment of the data for all endpoints the test material was considered unlikely to have the potential to cause severe ocular irritancy in vivo.
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 T000625 in 3 male rabbits (after 4 hours of exposure to 0.5 g of test item/animal). Skin reactions were recorded 1, 24, 48 and 72 hours after exposure (removal of the dressing, gauze patch and test item) and scored according to the Draize scale.

No evidence of skin irritation was noted. The test item did not meet the criteria for classification as irritant or corrosive to the skin according to the criteria of the CLP Regulation (EC) No 1272/2008.

 

The in vitro skin irritation study has been waived because adequate data from an in vivo skin irritation study are available.

 

Eye irritation:

Eurlings (2016) investigated the eye hazard potential of the test item by an in vitro bovine corneal opacity-permeability (BCOP) assay. This K1 study was selected as key study. An amount of 330 to 397 mg of T000625 (as supplied) was applied pure for 240 minutes in the first test. The test was repeated, however, this was not needed since the IVIS scores of the eyes treated with test items were within the same category. 

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). In the first test, the test item did not induce ocular irritation through both endpoints, resulting in a mean in vitro irritancy score of 0.4 (-1.5 to 2.3) after 240 minutes of treatment. In the second test, a mean in vitro irritancy score of -2.1 (4.0 to -0.6) was calculated after 240 minutes of treatment. Since the test item induced an IVIS≤3 in both tests, no classification is required for eye irritation or serious eye damage. In both tests, the acceptability criteria were met and it was concluded that the test conditions were adequate and the test system functioned properly.

 

In addition, a rabbit enucleated eye test (REET) was performed by Sanders (2004) to assess the ocular irritancy potential of T000625 (K2, supporting study). Five enucleated eyes of New Zealand White rabbits were treated with 0.1 mL (approx. 85 mg) (undiluted) of T000625. Corneal opacity, corneal swelling and fluorescein uptake were observed at 60, 120, 180 and 240 minutes after application and scored. No indication of irritation was noted. The test item was considered unlikely to have the potential to cause severe ocular irritancy in vivo.

Justification for classification or non-classification

Skin irritation:

According to an in vivo acute dermal irritation study, no evidence for skin irritation was noted for T000625. 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:

In the key, in vitro eye irritation study (BCOP) , T000625 showed no irritating effects. No classification is required for eye irritation or serious eye damage according to the criteria of the CLP Regulation (EC) No 1272/2008..