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Administrative data

Description of key information

Skin Irritation

A Skin irritation study for test chemical was conducted on five adult male patients as in a preliminary study of a maximization test. The test chemical was applied at a 4% concentration under occlusion for 48 h to the back each patients. There was no irritation seen in any subjects. Hence the test chemical considered to be not irritating to the skin of treated subjects.

Eye Irritation

The ocular irritation potential of test article was determined according to the OECD 492 test guideline followed for this study. The MatTek EpiOcular™ model was used to assess the potential ocular irritation of the test articles by determining the viability of the tissues following exposure to the test article via MTT. The mean % tissue viability of test substance was determined to be 97.1%. Hence, under the experimental test condition it was concluded that test substance is considered to be not irritating to the human eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
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:
data from handbook or collection of data
Justification for type of information:
Data is from peer reviewed journal
Qualifier:
according to guideline
Guideline:
other: As mentioned below
Principles of method if other than guideline:
To determine the skin irritation potential of test chemical.
GLP compliance:
not specified
Species:
human
Strain:
other: not applicable
Details on test animals or test system and environmental conditions:
Sex: male
Type of coverage:
occlusive
Preparation of test site:
not specified
Vehicle:
other: Petrolatum
Controls:
not specified
Amount / concentration applied:
4%
Duration of treatment / exposure:
48 hours
Observation period:
48 hours
Number of animals:
five adult male patients
Details on study design:
- Area of exposure: Back of humans
- Type of wrap if used: closed occlusive patch
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
48 h
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
There was no irritation seen in any subjects.
Interpretation of results:
other: Not irritating
Conclusions:
The test chemical was tested at a concentration of 4 % in petrolatum which produced no irritation in a 48-hr closed-patch test in human subjects.
Executive summary:

Skin irritation study for test chemical was conducted on five adult male patients as in a preliminary study of a maximization test. The test chemical was applied at a 4% concentration under occlusion for 48 h to the back each patients. There was no irritation seen in any subjects. Hence the test chemical considered to be not irritating to the skin of treated subjects.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May 05, 2017 to July 12, 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Data is from experimental study report.
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)
Principles of method if other than guideline:
The purpose of this study was to assess potential for the test article to be ocular irritants. The ocular irritation potential of a test article Benzyl butyrate (CAS No.- 103-37-7) may be predicted by measurement of its cytotoxic effect, as reflected in the 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay, in the MatTek EpiOcular™ model (MatTek Corp., Ashland, MA).


GLP compliance:
yes
Species:
human
Strain:
other: Not applicable
Details on test animals or tissues and environmental conditions:
- Description of the cell system used:
The normal human-derived keratinocytes were cultured at the air-liquid interface in a chemically defined medium on a permeable polycarbonate insert (surface 0.5 cm2). They were cultured in chemically defined serum free medium to form a multi-layered epithelium similar to that found in native corneal mucosa. Each lot of tissues was Quality Assured by MatTek according to specific QC standards including: histology, tissue viability (MTT mean optical density), reproducibility (SD) and tissue thickness.

- Test System Identification
All of the EpiOcular™ 3-dimensional human tissues used in this study were identified by the date of arrival and the lot number. Certificate of Analysis for the tissues is included in this report. Tissue plates were appropriately labeled with study information. Bias was not a factor in this test system.

- Justification of the test method and considerations regarding applicability
Human Corneal Epithelia (HCE) by MatTek, Inc.:
The test articles and controls were evaluated for potential ocular irritancy using the EpiOcular™ 3 dimensional human tissue model purchased from MatTek Corporation (Ashland, MA). This model consists of normal human keratinocytes cultured on a permeable synthetic membrane at the air-liquid interface in a chemically defined medium. The cells form a stratified, squamous corneal epithelium resembling the corneal mucosa of the human eye. This model has been used with several common tests of cytotoxicity including MTT and interleukin 1-alpha (IL-1α). A growing body of evidence indicates that EpiOcular™ effectively provides a non-animal means to assess potential irritancy. The EpiOcular™ model closely mimics the human corneal mucosa and thus provides an important in vitro approach in the evaluation of ocular irritancy and toxicity. Each lot of tissues was Quality Assured by MatTek, Inc. according to specific QC standards including: histology (cell layers), tissue viability (MTT mean optical density) and reproducibility (SD).


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): 50 µL
- Concentration (if solution): neat (undiluted)

VEHICLE (no vehicle)
- Amount(s) applied (volume or weight with unit): none
- Concentration (if solution): none
- Lot/batch no. (if required): none
- Purity: none

NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 50 µL
- Concentration (if solution): neat

POSITIVE CONTROL
- Amount(s) applied (volume or weight): 50 µL
- Concentration (if solution): neat
Duration of treatment / exposure:
Tissues were exposed for approximately 30 minutes for liquid test article and controls, at approximately 37°C, 5% CO2 in a humidified incubator.
Observation period (in vivo):
Not applicable
Duration of post- treatment incubation (in vitro):
Following the post soak, the tissues were rinsed and incubated at approximately 37°C, 5% CO2 in a humidified incubator for a post-exposure recovery time totaling ~2 hours for liquid test article and controls.
Number of animals or in vitro replicates:
3 tissues were used for test compound and control.
Details on study design:
- Details of the test procedure used
The tissues were exposed to the test article Benzyl butyrate neat (undiluted). EpiOcular™ tissues were purchased from MatTek. Quality control of the tissues was performed by MatTek and the Certificate of Analysis (CoA) for the tissues is provided and is kept in the study binder. Tissues were exposed for approximately 30 minutes for liquid test articles and controls, at approximately 37°C, 5% CO2 in a humidified incubator. After the exposure, the test article was rinsed off the tissues and the tissues were soaked in media for ~12 minutes for liquid test articles and controls. Following the post soak, the tissues were rinsed and incubated at approximately 37°C, 5% CO2 in a humidified incubator for a post-exposure recovery time totaling ~2 hours for liquid test article and controls. Tissue viability was assessed by 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.

- MTT Auto reduction and colouring assessment
MTT Pre-test
The test article was assessed for the potential to interfere with the assay. Approximately 50 µL of liquid test article Benzyl butyrate was added to 1 mL of MTT media (~1 mg/mL) and incubated in a humidified incubator at approximately 37°C and approximately 5% CO2 for 2 hours, 55 minutes and 02 seconds. 50 µL of ultrapure water was used as a negative control.

- Test Article Color Test
Approximately 50 µL of Benzyl butyrate was added to 1.0 mL of ultrapure water and 2.0 mL isopropanol and incubated in a humidified incubator at approximately 37°C and approximately 5% CO2 for 2 hours, 04 minutes and 35 seconds. Samples were then added to the wells of a clear 96-well plate and the plate was read on a BioTek Synergy H4 (or equivalent) plate reader set to 570 nm. Test articles that tested positive for excessive coloration (OD >0.08) were assessed on living-tissue controls that were incubated in both culture media and MTT media as well (n=3 for both conditions).

- MTT Assay
After the recovery period, the MTT assay was performed on run 1 tissues by transferring the tissues to 24-well plates containing 300 µL MTT medium (1.0 mg/mL). After 2 hours 50 minutes and 14 seconds (liquids) of MTT incubation at approximately 37°C, approximately 5% CO2 in a humidified incubator, the tissues were rinsed twice with DPBS. The blue formazan salt was extracted by submerging tissues in 2 mL isopropanol in a 24-well plate. The extraction for liquid exposed tissues was overnight incubation (22 hours 17 minutes and 52 seconds) with a 20 minute 24 second shake the following morning. The optical density of the extracted formazan (200 µL/well of a 96-well plate) was determined using a Synergy H4 spectrophotometer at 570 nm. Relative cell viability was calculated for each tissue as % of the mean negative control tissues.

- Evaluation of Test Article in the cell Models
1. Cell System:
Upon receipt, the MatTek EpiOcular™ tissue cultures were placed in 1.0 mL of fresh Maintenance medium (in a 6-well plate) for 55 minutes and 16 seconds. The tissues were not incubated overnight.

2. Control and Test Article Exposures:
20 µL of calcium and magnesium free DPBS was added to each tissue and the tissues placed back into the incubator for 31 minutes 00 seconds. The controls and the test article will be applied topically to tissues by pipette. Three tissues will be used per test compound and control.

a)Controls:
50 µL of negative control sterile ultrapure water, positive control methyl acetate were added to the tissues. The tissues were placed into the ~37°C humidified incubator with 5% CO2 for the approximately 30 minute exposure time.

b)Test Article:
50 µL of Benzyl butyrate were added to the tissues. The tissues were placed into the ~37°C humidified incubator with 5% CO2 for the approximately 30 minute exposure time.

3. Post exposure treatment:
After the exposure, the tissues were rinsed 20 to 25 times with ~1 mL of DPBS to remove test material. The apical surface was gently blotted with a cotton swab and cultures were immediately transferred to a 12-well plate containing 5 mL of media per well. Tissues exposed to liquid test articles (and the respective control) were incubated, submerged in the media for ~12 minutes at room temperature. Tissuses were then transferred to 6-well plates containing 1.0 mL fresh Maintenance medium per well and incubated for a post-exposure recovery period for 2 hours 01 minutes at approximately 37 degC, 5% CO2 in a humidified incubator.

- Doses of test chemical and control substances used
Test Article:
50 µL of Benzyl butyrate were added to the tissues. The tissues were placed into the ~37°C humidified incubator with 5% CO2 for the approximately 30 minute exposure time.

Controls:
50 µL of negative control sterile ultrapure water, positive control methyl acetate were added to the tissues. The tissues were placed into the ~37°C humidified incubator with 5% CO2 for the approximately 30 minute exposure time.

- Duration and temperature of exposure, post-exposure immersion and post-exposure incubation periods:
Tissues were exposed for approximately 30 minutes for liquid test article and controls, at approximately 37°C, 5% CO2 in a humidified incubator.
Following the post soak, the tissues were rinsed and incubated at approximately 37°C, 5% CO2 in a humidified incubator for a post-exposure recovery time totaling ~2 hours for liquid test article and controls.

- Justification for the use of a different negative control than ultrapure H2O (Not applicable)

- Justification for the use of a different positive control than neat methyl acetate (Not applicable)


- Number of tissue replicates used per test chemical and controls: 3 tissues were used for test compound and control.

- Description of the method used to quantify MTT formazan
The blue formazan salt was extracted by submerging tissues in 2 mL isopropanol in a 24-well plate. The extraction for liquid exposed tissues was overnight incubation (22 hours 17 minutes and 52 seconds) with a 20 minute 24 second shake the following morning. The optical density of the extracted formazan (200 µL/well of a 96-well plate) was determined using a Synergy H4 spectrophotometer at 570 nm.

- Description of evaluation criteria used including the justification for the selection of the cut-off point for the prediction model
Calculations and Statistical Methods
MTT Assay
Blanks:
·  The OD mean from all replicates for each plate (ODblank).

Negative Controls (NC):
·  The blank corrected value was calculated: ODNC= ODNCraw– ODblank.
·  The OD mean per NC tissue was calculated.
·  The mean OD for all tissues corresponds to 100% viability.
·  The mean, standard deviation (SD), standard error of the mean (SEM) and the percent coefficient of variation (% CV) was calculated.

ODblank= optical density of blank samples (isopropanol alone).
ODNCraw= optical density negative control samples.
ODNC= optical density of negative control samples after background subtraction.

Positive Control (PC):
·        Calculate the blank corrected value: ODPC= ODPCraw– ODblank.
·        The OD mean per PC tissue was calculated.
·        The viability per tissue was calculated: %PC = [ODPC/ mean ODNC] x 100.
·        The mean viability for all tissues was calculated: Mean PC = Σ %PC / number of tissues.
·        The standard deviation (SD), standard error of the mean (SEM) and the percent coefficient of variation (% CV) was calculated.
ODPCraw= optical density positive control samples.
ODPC= optical density of positive control samples after background subtraction.

Tested Articles:
·  Calculate the blank corrected value ODTT= ODTTraw– ODblank.
·  The OD mean per tissue is calculated.
·  The viability per tissue is calculated: %TT = [ODTT/ mean ODNC] x 100.
·  The mean viability for all tissues is calculated: Mean TT = Σ %TT / number of tissues.
·  The standard deviation (SD) and the percent coefficient of variation (% CV)for the controls and the test articles will be calculated.
ODTTraw= optical density test article samples.
ODPC= optical density of test article samples after background subtraction.

Data Correction Procedure for MTT Interfering Compounds
True viability = Viability of treated tissue – Interference from test article = ODtvt – ODkt where ODkt = (mean ODtkt – mean ODukt).
ODtvt = optical density of treated viable tissue
ODkt = optical density of killed tissues
ODtkt = optical density of treated killed tissue
ODukt = optical density of untreated killed tissue (NC treated tissue)

Data Correction Procedure for Colored Compounds
True viability = Viability of treated tissue incubated in MTT media – Viability of treated tissue incubated in media without MTT = ODtvt – ODvt.
ODtvt = optical density of treated viable tissue incubated in MTT media
ODvt = optical density of viable tissues incubated in media alone.

Proposed Statistical methods
The mean, standard deviation (SD) and the percent coefficient of variation (% CV) for the controls and the test article will be calculated.

- Evaluation of data
The results of the assay was evaluated and compared to negative control.

Table: Irritancy Prediction
In VitroResults In VivoPrediction
Mean tissue viability ≤60% Irritant (I) – Category 1 or 2
Mean tissue viability >60% Non-irritant (NI) – No Category

- Assay quality controls
- Negative Controls (NC)
The assay is meeting the acceptance criterion if the mean viability of the NC in terms of Optical Density (OD570) of the NC tissues (treated with sterile ultrapure water) in the MTT assay are >0.8 to <2.5. This is an indicator of tissue viability following shipping and conditions under use.
 
- Positive Controls (PC)
Methyl acetate was used as a PC and tested concurrently with the test article. The assay is meeting the acceptance criteria if the viability of the PC is <50% of the negative control.
 
- Standard Deviation (SD)
Each test of ocular irritancy potential is predicted from the mean viability determined on 3 single tissues. The assay meets the acceptance criteria if SD calculated from individual percent tissue viabilities of the replicates is <18% for three replicate tissues.

 
Irritation parameter:
other: mean % tissue viability
Run / experiment:
Run 1
Value:
97.1
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Other effects / acceptance of results:
The MTT data show the assay quality controls were met, as the OD of the negative control tissues was between 0.981 and 1.284 in run 1. Also, the positive control, methyl acetate, reduced tissue viability to be 22.1% (for 30 minute exposures with liquids) of negative control in run one and the standard deviation (SD) calculated from individual percent tissue viabilities of the test article exposed replicates was 6.0 passing the acceptance criteria.



Interpretation of results:
other: not irritating
Conclusions:
The ocular irritation potential of test article was determined according to the OECD 492 test guideline followed for this study. The mean % tissue viability of test substance was determined to be 97.1%. Thus, the test substance was considered to be "not irritating" to the human eye.
Executive summary:

The ocular irritation potential of test chemical was determined according to the OECD 492 test guideline followed for this study. The MatTek EpiOcular™ model was used to assess the potential ocular irritation of the test articles by determining the viability of the tissues following exposure to the test article via MTT. The objective of this study was to assess the ocular irritation potential of test article. Tissues were exposed to liquid test article and controls for ~30 minutes, followed by a ~12 minute post-soak and approximately 2 hour recovery after the post-soak.  The viability of each tissue was determined by MTT assay. The MTT data show the assay quality controls were met, as the OD of the negative control tissues was between 0.981 and 1.284 in run 1. Also, the positive control, methyl acetate, reduced tissue viability to be 22.1% (for 30 minute exposures) of negative control in run one and the standard deviation (SD) calculated from individual percent tissue viabilities of the test article exposed replicates was 6.0 passing the acceptance criteria. The mean % tissue viability of test substance was determined to be 97.1%. Hence, under the experimental test condition it was concluded that test substance was considered to be not irritating to the human eye and being classified as “Not classified’’ as per CLP Regulation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation:

Various studies have been investigated for the test chemical to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in-vivo experiments conducted for target chemical in humans and rabbits. The results are mentioned below:

Skin irritation study for test chemical was conducted on five adult male patients as in a preliminary study of a maximization test. The test chemical was applied at a 4% concentration under occlusion for 48 h to the back each patients. There was no irritation seen in any subjects. Hence the test chemical considered to be not irritating to the skin of treated subjects.

This result is supported by a skin irritation study was performed in humans to assess the irritation potential of test chemical. When the test chemical was tested 4% in petrolatum for 48 hours closed patch test, no known signs of irritation was observed in treated subjects. Thus the test chemical was considered to be not irritating to the skin of treated subjects.

These results are further supported by a similar skin irritation study conducted on rabbits to determine the irritation efficacy of test chemical. No irritation was observed when test chemical was applied topically to five rabbits at a dose of 5000 mg/kg. Hence the test chemical was considered to be not irritating to the skin of rabbits.

These results are also supported by another skin irritation study conducted on rabbits to determine the skin irritating effects caused by the chemical. The undiluted test chemical was applied on the intact and abraded skin of each rabbit for 24 hours under occlusive condition. As no known signs of irritation was observed, the test chemical was considered to be not irritating to the skin of treated rabbits under occlusive condition.

All of the above results are lent support by a skin irritation study of test chemical conducted on 13 male and female patients to assess the irritation potential of test chemical. The test chemical was applied under an adhesive bandage to the arm of 13 male and female patients for 24 h. The sites were observed for five days at 24 h intervals. The test chemical caused mild irritation in one subject only while the remaining subjects had not developed any signs of irritation. Thus the test chemical was considered to be not irritating to the skin of human subjects.

Based on the above studies for target chemical, it can be concluded that the test chemical is unable to cause dermal irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Eye Irritation:

In different studies, the test chemical has been investigated for potential for ocular irritation to a greater or lesser extent. The studies are based on in- vitro and in-vivo experimental studies performed using the test chemical and the results are mentioned below:

The ocular irritation potential of test article was determined according to the OECD 492 test guideline followed for this study. The MatTek EpiOcular™ model was used to assess the potential ocular irritation of the test articles by determining the viability of the tissues following exposure to the test article via MTT. The objective of this study was to assess the ocular irritation potential of test article. Tissues were exposed to liquid test article and controls for ~30 minutes, followed by a ~12 minute post-soak and approximately 2 hour recovery after the post-soak.  The viability of each tissue was determined by MTT assay.  The MTT data show the assay quality controls were met, as the OD of the negative control tissues was between 0.981 and 1.284 in run 1. Also, the positive control, methyl acetate, reduced tissue viability to be 22.1% (for 30 minute exposures) of negative control in run one and the standard deviation (SD) calculated from individual percent tissue viabilities of the test article exposed replicates was 6.0 passing the acceptance criteria. The mean % tissue viability of test substance was determined to be 97.1%. Hence, under the experimental test condition it was concluded that test substance is considered to be not irritating to the human eye.

The in vitro result is supported by an acute Ocular Irritation/corrosion Study performed in Rabbits as per OECD guideline No. 405 for the test chemical. Rabbits free from injury of eye were selected for the study. The eyes of all the rabbits were examined 24 hours prior to treatment. One eye of each rabbit served as control and other as treated. Control eye was left untreated whereas;0.1 ml of test item (as such)was instilled in the other (treated) eye of rabbits.The eye was observed at 1, 24, 48, 72 hours after test item instillation. Ophthalmoscope was used for scoring of eye lesions. In the initial test,0.1 ml of test itemwas applied into the conjunctival sac of the right eye of Animal No.1. The left eye of the rabbit served as the control. Animal No. 1 presented ocular lesions at 1 hour observation period. Hence the confirmatory test was conducted on additional two rabbits (Animal No. 2 and 3);0.1 ml of test item was instilled into the conjunctival sac of right eye and left eye served as the control. Ocular lesions were observed at 1, 24 and 48 hour in Animal Number 2 whereas in Animal Number 3 ocular lesions presented only at 1 hour observation period. Untreated eye of the treated rabbits was normal throughout the experimental period of 72 hours. The following grading scores were observed in treated eye of tested rabbits. Observation at 1 hour after instillation of test item revealed: Cornea-No ulceration or opacity in all 3 animals; Area of Opacity-Zero in all the animals;Iris:Normal in all the animals.Conjunctivae -Some blood vessels definitely hyperaemic (injected) in all the animals;Chemosis:Some swelling above normal (includes nictating membranes) were observed in animal number 1 and 3 whereas animal number 2 was normal. Observation at 24 hours after instillation of test item revealed: Cornea-No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals;Iris:Normal in all the animals.Conjunctivae -Some blood vessels definitely hyperaemic (injected) was observed in animal no. 2. Animal no. 1 and 3 recovered to normal;Chemosis:No swelling was observed in all the Animals. At 24 hours observation the rabbits were examined for corneal epithelium cell damage using sodium fluorescein strips and noticed 0 % damage in Animal Nos 1, 2 and 3, respectively. Observation at 48 and 72 hours after instillation of test item revealed: Cornea-No ulceration or opacity in all the animals; Area of Opacity-Zero in all the animals;Iris:Normal in all the animals. Conjunctivae -Some blood vessels definitely hyperaemic (injected) was observed in animal no. 3 at 48 hours which was recovered to normal at 72 hours observation whereas blood vessels were normal in Animal Numbers 1 and 3 at 48 and 72 hours observation;Chemosis: No swelling was observed in all the animals. The individual mean score for Animal Nos. 1, 2 and 3at 24, 48, 72 hoursfor Corneal opacity, iris, conjunctiva, chemosis were found 0.00, 0.00, 0.00, 0.00 ; 0.00, 0.00, 0.67, 0.00 and 0.00, 0.00, 0.00, 0.00, respectively. Under the experimental conditions tested, eye irritation and reversibility of effects on eyes of rabbits was observed at 72 hours.  Under the experimental conditions tested, eye irritation and reversibility of effects on eyes of rabbits was observed at 72 hours. Hence under the experimental test conditions, the test chemical is “Non Irritant” to New Zealand White Male rabbit eyes.

These results are further supported by a similar eye irritation test conducted to evaluate the irritation potential of test chemical. The test was performed in accordance with the Draize test procedure. Six albino rabbits received a 0.1-mL aliquot of benzyl acetate in the right eye.The left eye served as the control. The eyes were examined at 24, 48 and 72 h; then again on days 4 and 7.After 7 days of observation, no irritation was observed. Hence the test chemical was considered to be not irritating to the eyes of albino rabbits. 

Based on the available results, it can be concluded that the test chemical is unable to cause ocular irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Justification for classification or non-classification

Based on the available results, the test chemical is not likely to cause any irritation to skin and eyes. Hence the test chemical can be considered to be not irritating to skin and eyes, and classified under the category "Not Classified" as per CLP Regulation.

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