Registration Dossier

Administrative data

Description of key information

Skin irritation:

The dermal irritation potential of test article Hydratropaldehyde (CAS No.- 93-53-8) was determined according to the OECD 439 test guideline followed for this study. The Mean % tissue viability compared to negative control (n=3) of the test substance Hydratropaldehyde was determined to be 0.0%. Thus, substance Hydratropaldehyde (CAS No.- 93-53-8) is considered to be a skin irritant in Category 2 as per CLP Regulation.

Eye irritation:

The ocular irritation potential of test article Hydratropaldehyde (CAS No.- 93-53-8) was determined according to the OECD 492 test guideline followed for this study. The mean % tissue viability of test substance Hydratropaldehyde was determined to be 29.6%. Thus, substance Hydratropaldehyde (CAS No.- 93-53-8) is considered to be an eye irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May 05, 2017 to July 17, 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:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Principles of method if other than guideline:
The purpose of this study was to assess potential for the test articles to be dermal irritants. The dermal irritation potential of test article Hydratrop aldehyde (CAS No.- 93-53-8) may be predicted by measurement of their cytotoxic effect, as reflected in the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay, in the MatTek EpiDerm™ model (MatTek Corp., Ashland, MA).




GLP compliance:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Test material identity: Hydratropaldehyde (2-Phenylpropionaldehyde, 97%)
- Source of test material: Alfa Aesar
- Lot No.of test material: 10177315
- Date of analysis: 25.01.2013
- Expiration date of the lot/batch: 25.01.2018
- Purity test date: 96.6%
- Appearance (colour): Clear colourless liquid

RADIOLABELLING INFORMATION (Not applicable)
- Radiochemical purity: N/A
- Specific activity: N/A
- Locations of the label: N/A
- Expiration date of radiochemical substance: N/A

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Freeze storage
- Stability under test conditions: No data available
- Solubility and stability of the test substance in the solvent/vehicle: No data available
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No data available

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Test articles is tested as provided (neat).
- Preliminary purification step (if any): No data available
- Final dilution of a dissolved solid, stock liquid or gel: No data available
- Final preparation of a solid: No data available

FORM AS APPLIED IN THE TEST (if different from that of starting material): Liquid

OTHER SPECIFICS: No data available
Test system:
human skin model
Source species:
human
Cell type:
non-transformed keratinocytes
Cell source:
other: EpiDerm™ 3-dimensional human tissues used in this study
Source strain:
other: Not applicable
Details on animal used as source of test system:
- 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 epidermis. 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 EpiDerm™ 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 are included in this report. Tissue plates were appropriately labeled with study information.
Justification for test system used:
The 3-Dimensional Human Dermal Epithelial Model (EpiDerm™, MatTek, Ashland, MA) is made up of normal human keratinocytes in serum free medium. The cells form an epithelial tissue that consists of organized basal, spinous, granular, and cornified layers analogous to those found in vivo. The EpiDerm™ model also contains epidermis-specific differentiation markers such as pro-filaggrin, the K1/K10 cytokeratin pair, involucrin, and type I epidermal transglutaminase, as well as keratohyalin granules, tonofilament bundles, desmosomes, and a multi-layered stratum corneum containing intercellular lamellar lipid layers arranged in patterns characteristic of in vivo epidermis. 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). Tissue plates were appropriately labeled with study information. Bias was not a factor in this test system.


Vehicle:
unchanged (no vehicle)
Details on test system:
The tissues were exposed to the test article Hydratropaldehyde neat (undiluted) on June 28, 2017 (Run 1 of 1). EpiDerm™ 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 1 hour, with 35 minutes in an approximately 37°C, 5% CO2 humidified incubator and the remaining 25 minutes at room temperature. Following the exposure time, the tissues were rinsed and placed in fresh media for approximately 24 hours. The media was then changed again and the tissues were incubated in fresh media for another ~18 hours for a total of approximately 42 hour post-exposure recovery period. The tissue viability was then assessed by MTT assay. The tissue CoA was used instead of verification of barrier properties of the tissue.

MTT and Color Pre-tests
Pretesting for MTT auto-reduction and coloring was not performed for this study but was based on the results obtained from another study (CYP1690_R1b).

MTT Assay
Following the rinsing period, the MTT assay was performed by transferring the tissues to 24-well plates containing 300 µL MTT medium (1.0 mg/mL). After 2 hours, 57 minute and 25 second MTT incubation at approximately 37°C, approximately 5% CO2 in a humidified incubator, the blue formazan salt was extracted by submerging tissues in 2 mL isopropanol in a 24-well plate. The extraction time was approximately 2 hours 04 minutes and 11 seconds with gentle shaking. 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 is 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 EpiDerm™ tissue cultures were placed in 0.9 mL of fresh Maintenance medium (in a 6-well plate). The culture inserts are incubated for ~one hour. The tissues were then transferred to 6-well plates containing 0.9 mL fresh Maintenance medium and they were incubated overnight at ~37°C, 5% CO2 in a humidified incubator.

2. Control and Test Article Exposures: On the day of dosing, the tissues are then removed from the incubator and the controls and the test articles are applied topically to tissues by pipette. Tissues were exposed to controls and the test articles for one hour, with ~35 minutes in a 37°C, 5% CO2 humidified incubator and the remaining 25 minutes at room temperature.

a) Controls
30 µL of negative control DPBS, positive control 5% SDS was applied topically to the tissue and gently spread by placing a nylon mesh on the apical surface of each tissue, if necessary.

b) Test Articles
30 µL of the test article Hydratropaldehyde was applied topically to the tissue and gently spread by placing a nylon mesh on the apical surface of each tissue, if necessary.

3. Post-exposure treatment
After the 1 hour exposure, the tissues were rinsed 20 to 25 times with 1 mL of DPBS. The apical surface was gently blotted with a cotton swab. The tissues were placed in 0.9 mL of fresh Maintenance medium (6-well plate) for either 25 hours, 38 minutes and 23 seconds or for 24 hours, 10 minutes and 09 seconds (as there were numerous tissues, they had to be broken down into 2 sets to complete dosing in a timely manner). After this initial ~24 hour incubation, the tissues were placed in 6-well plates containing 0.9 mL fresh Maintenance medium and incubated for another 17 hours, 03 minutes and 34 seconds prior to performing the MTT assay, for a total of an approximately 42 hour post-exposure incubation.

RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: The EpiDerm™ 3 dimensional human tissue model
- Tissue Lot number(s): 26459
- Date of initiation of testing: 6/08/2017

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 37°C
- Temperature of post-treatment incubation (if applicable): 37°C

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: Twice

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 300 µL MTT medium (1.0 mg/mL).
- Incubation time: After 2 hours, 57 minute and 25 second MTT incubation
- Spectrophotometer: Synergy H4 spectrophotometer
- Wavelength: 570 nm
- Filter: No data
- Filter bandwidth: No data
- Linear OD range of spectrophotometer: No data

NUMBER OF REPLICATE TISSUES: 3

CALCULATIONS and STATISTICAL METHODS
All data were background subtracted before analysis. MTT data are presented as % viable compared to negative control. Data were generated as follows:

MTT Assay
Blanks:
·        The optical density (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.

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.

Tested compound :
·        Calculate the blank corrected value ODTT= ODTTraw– ODblank.
·        The OD mean per tissue was calculated.
·        The viability per tissue was calculated: %TT = [ODTT/ mean ODNC] x 100.
·        The mean viability for all tissues was calculated: Mean TT = Σ %TT / number of tissues.
·        The standard deviation (SD), standard error of the mean (SEM) and the percent coefficient of variation (% CV) was calculated.

Data Correction Procedure for MTT Interfering Compounds (if applicable)
True viability = Viability of treated tissue – Interference from test article = ODtvt– ODktwhere 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 (if applicable)
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
 
- Evaluation of data
The results of the assay was evaluated and compared to negative control.

Table: Criteria for in vitro Interpretation:
In VitroResults In VivoPrediction
Mean tissue viability ≤50% Irritant (I), R38
Mean tissue viability >50% Non-irritant (NI)

- Assay quality controls
- Negative Controls (NC)
The Dulbecco’s phosphate buffered saline (DPBS) was used as a NC. The assay passed all acceptance criteria if the ODs of the negative control exposed tissues were between ≥0.8 and ≤2.8.
 
- Positive Controls (PC)
5% solution of sodium dodecyl sulfate was used as a PC. The assay is meeting the acceptance criteria if the viability of the PC is ≤20% of the negative control.
 
- Standard Deviation (SD)
The standard deviation (SD) calculated from individual percent tissue viabilities of the test article exposed replicates was ≤18.
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 30 µL
- Concentration (if solution): neat

VEHICLE (Not used)
- 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): 30 µL
- Concentration (if solution): neat

POSITIVE CONTROL
- Amount(s) applied (volume or weight): 30 µL
- Concentration (if solution): 5% solution of sodium dodecyl sulfate
Duration of treatment / exposure:
The exposure times were approximately 1 hour, with ~35 minutes exposure in the incubator and ~25 minutes at room temperature.
Duration of post-treatment incubation (if applicable):
For a total of an approximately 42 hour post-exposure incubation.
Number of replicates:
3 tissues were used for test compound and control.
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
Run 1
Value:
0
Vehicle controls validity:
not specified
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
positive 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 1.195 and 1.430. Also, the positive control, 5% sodium dodecyl sulfate (SDS), reduced tissue viability to 4.5% of negative control and the standard deviation (SD) calculated from individual percent tissue viabilities of the test article exposed replicates was 0.0 passing the acceptance criteria.
Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Conclusions:
The dermal irritation potential of test article Hydratropaldehyde (CAS No.- 93-53-8) was determined according to the OECD 439 test guideline followed for this study. The Mean % tissue viability compared to negative control (n=3) of the test substance Hydratropaldehyde was determined to be 0.0%. Thus, substance Hydratropaldehyde (CAS No.- 93-53-8) is considered to be a skin irritant in Category 1 as per CLP Regulation.
Executive summary:

The dermal irritation potential of test article Hydratropaldehyde (CAS No.- 93-53-8) was determined according to the OECD 439 test guideline followed for this study. The MatTek EpiDerm™ model was used to assess the potential dermal irritation of the test article by determining the viability of the tissues following exposure to the test article via MTT. The objective of this study was to assess the dermal irritation potential of test article. Tissues were exposed to test article and controls for ~one hour, followed by a 42 hour post-exposure recovery period. 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 1.195 and 1.430. Also, the positive control, 5% sodium dodecyl sulfate (SDS), reduced tissue viability to 4.5% of negative control and the standard deviation (SD) calculated from individual percent tissue viabilities of the test article exposed replicates was 0.0 passing the acceptance criteria.

 

The Mean % tissue viability compared to negative control (n=3) of the test substance Hydratropaldehyde was determined to be 0.0%.

 

Hence, under the experimental test conditions it was concluded that test substance Hydratropaldehyde (CAS No.- 93-53-8) is considered to be irritating to the human skin and being classified as ''Irritating to skin in Category 1” as per CLP Regulation.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data is from peer reviewed journal
Qualifier:
according to
Guideline:
other: as below
Principles of method if other than guideline:
Hydratropic aldehyde was administered undiluted into rabbit eyes and toxic effects were observed
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
No data
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
Full strength
Duration of treatment / exposure:
24 hours exposure
Observation period (in vivo):
no data
Number of animals or in vitro replicates:
Not reported
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 hours
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Conjunctival Irritation observed
Interpretation of results:
irritating
Conclusions:
Conjunctival irritation produced by undiluted hydratropic aldehyde in the rabbit eye cleared by 24 hours.
Since the irritation cleared by 24 hours, it can be concluded that hydratropic aldehyde is irritating to rabbit eyes
Executive summary:

Eye irritation study was carried out on rabbits.

Hydratropic aldehyde was administered undiluted into rabbit eyes and toxic effects were observed. Conjunctival irritation produced by undiluted hydratropic aldehyde in the rabbit eye cleared by 24 hours.

As though the irritation was cleared by 24 hours, it can be concluded that hydratropic aldehyde is irritating to rabbit eyes.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

In different studies, Hydratropaldehyde has been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vitro and in vivo experiments in rabbits along with human data for target chemical and its structurally similar read across substance, 1-phenylethanol [CAS: 98-85-1].

The dermal irritation potential of test article Hydratropaldehyde (CAS No.- 93-53-8) was determined according to the OECD 439 test guideline followed for this study. The MatTek EpiDerm™ model was used to assess the potential dermal irritation of the test article by determining the viability of the tissues following exposure to the test article via MTT. The objective of this study was to assess the dermal irritation potential of test article. Tissues were exposed to test article and controls for ~one hour, followed by a 42 hour post-exposure recovery period. 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 1.195 and 1.430. Also, the positive control, 5% sodium dodecyl sulfate (SDS), reduced tissue viability to 4.5% of negative control and the standard deviation (SD) calculated from individual percent tissue viabilities of the test article exposed replicates was 0.0 passing the acceptance criteria.

 

The Mean % tissue viability compared to negative control (n=3) of the test substance Hydratropaldehyde was determined to be 0.0%.

 

Hence, under the experimental test conditions it was concluded that test substance Hydratropaldehyde (CAS No.- 93-53-8) is considered to be irritating to the human skin and being classified as ''Irritating to skin in Category 2” as per CLP Regulation.

In a supporting study, the irritant effect by (D.L.J. Opdyke, 1975) of Hydratropaldehyde was assessed in human. Human volunteers were exposed to 2% in petrolatum concentration of Hydratropic aldehyde. They were exposed to 48 hrs closed patch test and found to be mild irritating. As Hydratropaldehyde was found to be mildly irritating in human volunteer, it can be concluded that Hydratropaldehyde can be classified as “skin irritant “in accordance with CLP criteria.

 

Further supported by the study where Hydratropic aldehyde applied full strength to intact or abraded rabbit skin for 24 hr under occlusion was severely irritating.

As per CLP regulation the chemical was found to be irritating.

Also in a supporting study Repeated Insult Patch test on Humans was conducted to evaluate the irritation potential of the Hydratropic aldehyde.

The test procedure was an adaptation of the repeated insulted patch procedure suggested by Draize(1959). Subjects were furnished by churches, Parent-Teachers Associations and similar organizations in suburban areas around Cincinnati. The test was initiated on 10 human volunteers but completed by 7. The test patch was one-inch square of Webril (absorbent. non-woven cotton fabric) affixed to the center of a 1 x 3-inch strip of adhesive elastic bandage material.The test bandages were specially prepared by Duke Laboratories, Inc.

Immediately before application to each subject 0.5 ml of sample was added to the Webril swatch and the bandage was then placed on the subject’s upper arm.The subjects removed the bandages 24 hours after application.

Under the conditions of the test , Hydratropic aldehyde caused occasional primary irritation on the test subjects.

As per above experiment chemical was found to be irritating.

Further supported by Repeated Insult Patch test on Humans was conducted to evaluate the irritation potential of the Hydratropic aldehyde. The test procedure was an adaptation of the repeated insulted patch procedure suggested by Draize(1959). Subjects were furnished by churches, Parent-Teachers Associations and similar organizations in suburban areas around Cincinnati. The test was initiated on 43 human volunteers but completed by 39.

The test patch was one-inch square of Webril (absorbent. non-woven cotton fabric) affixed to the center of a 1 x 3-inch strip of adhesive elastic bandage material.The test bandages were specially prepared by Duke Laboratories, Inc.

 

Immediately before application to each subject 0.5 ml of sample was added to the Webril swatch and the bandage was then placed on the subject’s upper arm.The subjects removed the bandages 24 hours after application.

Under the conditions of the test , Hydratropic aldehyde caused little or no primary irritation on the test subjects.

According to the above experiment the chemical was found to be irritating.

In a supporting study conducted on Read across substance methyl benzyl alcohol ,Preliminary irritation screen for a modified Draize sensitization study in Hartley strain albino guinea pigs was performed.

  The test compound was applied intradermally at a concentration of0.25%.Four animals of the same sex and weighing about 450 g were each injected intradermally on the shaved flanks with 0.1 ml aliquots of a range of concentration of test material in a suitable solvent.

 Slight irritation was noted at the tested concentration.

The test material methyl benzyl alcohol is slightly irritating to the skin of Guinea pigs. The chemical was found to be irritating.

On the basis of available information for the target and read across substance, the test substance Hydratropaldehyde can be considered as irritating to the skin, can be classified as a skin irritant , in accordance with the CLP criteria.

Eye irritation

The eye irritant effect by (D.L.J. Opdyke, 1975) of Hydratropaldehyde was assessed in rabbit.Eye irritation study was carried out on rabbits. Hydratropic aldehyde was administered undiluted into rabbit eyes and toxic effects were observed. Conjunctival irritation produced by undiluted hydratropic aldehyde in the rabbit eye cleared by 24 hours. It can be concluded that Hydratropic aldehyde is irritating to rabbit eye.Based on the above information the test substance Hydratropaldehyde was classified as eye irritant as per CLP regulation.

The eye irritation potential for Hydratropic aldehyde is estimated using OECD QSAR toolbox Version 3.3.The test substance Hydratropic aldehyde was estimated to be irritating in rabbit’s eye.It can be concluded that Hydratropic aldehyde is irritating to rabbit eye.Based on the above information that the test substance Hydratropaldehyde was classified as eye irritant as per CLP regulation.

In another supporting study by (Sustainability Support Services (Europe) AB has the letter of access, 2014) with similar substance (98-85-1) was assessed in rabbit.0.1 ml of test item was instilled in the other (treated) eye of each rabbit. The eye was observed at 1, 24, 48, 72 hour, day 7, day 14 and day 21 for animal no. 1 and 3 whereas at 1, 24, 48, 72 hour, day 7 and day 14 for animal no. 2 after test item instillation. Ophthalmoscope was used for scoring of eye lesions. In the initial test, 0.1 ml of test item (as such) was applied into the conjunctival sac of the right eye of animal no.1 whereas the left eye of the rabbit served as the control. As animal no. 1 showed no severe ocular lesions. Under the experimental conditions tested, all the three animals were fully reversible within an observation period of 14 for animal no. 2. and 21 days for animal no. 1 and 3.  Hence under the experimental test conditions, “1-phenylethanol (CAS No. - 98-85-1)” is“An Eye Irritant (Irritating to Eyes)”of New Zealand White Female rabbit eyes.

In another supporting study by (Carpenter, C.P. et al., 1946) with similar substance (98-85-1) was assessed in rabbit.Eye irritation study was conducted to evaluate the eye irritation potential of the test compound 1-pheny ethanol. Application of 0.005 mL of a 40% solution of alpha-methylbenzyl alcohol caused severe injury in rabbits (scored over 5 where 5 is severe injury; graded 7/10. the study suggests the chemical to be an eye irritant.

In another supporting study by (Carpenter, C.P. et al., 1946) with similar substance (98-85-1) was assessed in rabbit.2 mg of 1-phenylethanol instilled into rabbit eye caused severe irritation.

On the basis of available information for the target and read across substance, the test substance can be considered as irritating tothe eye, inaccordance with the CLP criteria.


Justification for selection of skin irritation / corrosion endpoint:
The irritant effect by (D.L.J. Opdyke, 1975) of Hydratropaldehyde was assessed in human. Human volunteers were exposed to 2% in petrolatum concentration of Hydratropic aldehyde. They were exposed to 48 hrs closed patch test and found to be mild irritating. As Hydratropaldehyde was found to be
mildly irritating in human volunteer.

Justification for selection of eye irritation endpoint:
Eye irritation study was carried out on rabbits. Hydratropic aldehyde was administered undiluted into rabbit eyes and toxic effects were observed. Conjunctival irritation produced by undiluted hydratropic aldehyde in the rabbit eye cleared by 24 hours. It can be concluded that Hydratropic aldehyde is irritating to rabbit eye.

Effects on skin irritation/corrosion: moderately irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

Based on the above information,the test substance Hydratropaldehyde can be considered as irritating to the skin and eye but not corrosive ,it can be classified as in skin and eye irritant category 2, in accordance with the CLP criteria.