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Administrative data

Description of key information

GLP OECD 437: IVIS=21.7, no preduction possible on eye irritation

GLP OECD 492: viability=3.5 %, irritant to the eye

GLP OECD 439: skin irritation assy was negative

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:
2015-04-23 - 2015-06-19
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
Qualifier:
according to
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Qualifier:
according to
Guideline:
other: Skinethic skin irritation test -42bis Standard operating procedure (SOP) 2009
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
Designation: Art. 803057
Synonym: 4-(Dimethylamino)benzaldehyde
Batch: S6886257
CAS-No.: 100-10-7
Assay (GC, area%): 99.6% (a/a)
Appearance: Grey-blue, crystalline powder
Released until: May 31, 2019
Storage: Tightly closed, dark at room temperature (15 to 25°C)
Test system:
human skin model
Source species:
human
Cell type:
non-transformed keratinocytes
Cell source:
foreskin from a single donor
Justification for test system used:
standard model
Vehicle:
unchanged (no vehicle)
Remarks:
No vehicle used in this study; The test item was applied neat to the tissues.
Details on test system:
CELL CULTURE
- Supplier: EpiSkin/SkinEthic Laboratories, Lyon, France)
- Source: human keratinocytes cultured on a polycarbonate filter in conditions which permit their terminal differentiation
- Format: 24 well plate
- Batch: 15-RHE-059
- Expires: May 18, 2015

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment: room temperature
- Temperature of post-treatment incubation: 37°C

REMOVAL OF THE TEST MATERIAL AND CONTROL
After the end of the treatment interval, the residual test item was removed immediately by gently rinsing with a minimum volume of 25 mL DPBS using a pipette. Excess DPBS was removed by gently shaking the inserts and blotting the bottom with blotting paper.

Control samples:
yes, concurrent negative control
Amount/concentration applied:
TEST MATERIAL: 16 mg of solid test material
NEGATIVE CONTROL: 16 µL (Dulbecco`s Phosphate-Buffered Saline)
POSITIVE CONTROL: 16 µL (5% aqueous solution of sodium dodecyl sulfate in deionised water)
Duration of treatment / exposure:
42 min (± 1 minute)
Duration of post-treatment incubation (if applicable):
42 hours (± 1 hour)
Number of replicates:
3
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
Experiment 1 / Run 1
Value:
95.6
Vehicle controls validity:
not applicable
Remarks:
The test item was applied neat to the tissues
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Other effects / acceptance of results:
OTHER EFFECTS:
- Visible damage on test system: none
- Direct-MTT reduction: none
- Colour interference with MTT: none

ACCEPTANCE OF RESULTS:
Acceptability of the Quality Control Data of the Skin Model with Reference to Historical Batch Data:
The negative control OD values were 2.366, 2.297 and 2.516 and, thus, in the range of ≥0.8 and ≤3.0.

Acceptability of the Positive and Negative Control:
After treatment with the negative control (DPBS-buffer) the mean OD was 2.393 (standard deviation: 4.68%) and, thus, higher than the historically established boundary of 1.388.
After treatment with the positive control (5% aqueous solution of sodium dodecyl sulfate) the mean viability value was 1.02% (standard deviation: 10.96%) and, thus, lower than the historically established boundary of 3.51%.
The standard deviation of the negative control and the positive control was ≤18%, respectively.

Test Substance Data Acceptance Criteria:
The standard deviation of the three tissues treated with the test item was 1.13% and, thus, ≤18%.

Therefore, the study fulfilled the validity criteria.


 Group Time / [min]  Mean OD  Mean Relative viability / [%]
 Negative Control 42  2.393 100 
 Positive Control 42

0.024

1.02

 Test Material

42

2.288

95.60

Interpretation of results:
not irritating
Remarks:
UN GHS: No Caterory (according to OECD TG 439)
Conclusions:
This study was performed according to GLP and the methods applied are fully compliant with OECD TG 439. The test material was not irritating in this in vitro assay.
Executive summary:

This study was performed according to GLP and the methods applied are fully compliant with OECD TG 439. The test material was negative in this in vitro assay.

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:
May 6, 2015 - July 13, 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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)
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
Designation: Art. 803057
Synonym: 4-(Dimethylamino)benzaldehyde
CAS-No.: 100-10-7
Batch: S6886257
Assay (GC, area%): 99.6% (a/a)
Appearance: Grey-blue, crystalline powder
Released until: May 31, 2019
Storage: Tightly closed, dark at room temperature (15 to 25°C)

PREPARATION OF THE TEST MATERIAL
The test item Art. 803057 was prepared as a 20% (w/v) suspension in a 0.9% sodium chloride solution. The stability in the vehicle was not investigated. The test item preparation was administered within <1 hour after preparation.
Vehicle:
physiological saline
Controls:
yes, concurrent vehicle
yes, concurrent positive control
Amount / concentration applied:
TEST MATERIAL: 750 µL (i.e. 150mg/750µL)

NEGATIVE / VEHICLE CONTROL: 750 µL

Designation: 0.9% sodium chloride solution
Supplier: B. Braun Melsungen AG, Germany
Batch: 13445011
Released until: September 2016

POSITIVE CONTROL: 750 µL

Designation: Art. 814223
Synonym: Imidazole
Supplier: Merck KGaA, Germany
Batch: S6746923
Released until: August 31, 2018
Imidazole was dissolved with 0.9% sodium chloride solution to a concentration of 20% (w/v)
Duration of treatment / exposure:
240 minutes
Number of animals or in vitro replicates:
in vitro: triplicate design
Irritation parameter:
in vitro irritation score
Run / experiment:
Run 1 / Experiment 1
Value:
21.7
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
not determinable
Other effects / acceptance of results:
OTHER EFFECTS:
- Visible damage on test system: No observations (e.g. tissue peeling, residual test chemical, non-uniform opacity patterns) were seen in a visually inspection of the corneas after treatment.

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: After treatment with the negative control (0.9% sodium chloride solution) the calculated IVIS was 0.7 and, thus, within three standard deviations of the current historical mean of the negative control (IVIS: -1.4 – 3.6).
- Acceptance criteria met for positive control: After treatment with the positive control (20% Imidazole) the calculated IVIS was 99.2 and, thus, also within two standard deviations of the current historical mean of the positive control (IVIS 74.7 – 138.6). Therefore, the study fulfilled the validity criteria.

Opacity
Permeability
IVIS
per cornea
per group
(mean value)
SD
Negative control
0.9% NaCl Solution
1.845
-0.003
1.800
0.7
1.0
0.383
0.000
0.388
-0.064
-0.004
-0.124
Positive control
20% Imidazole solution
64.464
2.223
97.807
99.2
2.0
59.362
2.808
101.486
67.395
2.058
98.263
Test item
Art. 803057
24.942
-0.002
24.910
21.7
3.1
18.783
-0.001
18.766
21.504
-0.005
21.427


Interpretation of results:
other: could not be determined
Conclusions:
Under the conditions of the present study, the eye hazard potential of the test item Art. 803057 (4-(Dimethylamino)benzaldehyde) cannot be predicted.
Executive summary:

This study was performed according to GLP and the methods applied are fully compliant with OECD TG 437. Under the conditions of the present study, the eye hazard potential of the test item Art. 803057 (4-(Dimethylamino)benzaldehyde) cannot be predicted.

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21.11.2016 - 09.03.2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
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)
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
Identification:
Art. 803057 (4-(Dimethylamino)benzaldehyde)
Batch:
S6886257
Purity:
99.6% (GC, area%)
Appearance:
Grey-blue, crystalline powder
Expiry Date:
31 May 2019
Storage Conditions:
At room temperature, protected from light*
Stability in Solvent:
Not relevant
Vehicle:
unchanged (no vehicle)
Controls:
yes
yes, concurrent positive control
yes, concurrent negative control
Amount / concentration applied:
50 mg
Duration of treatment / exposure:
6 h
Number of animals or in vitro replicates:
triplicate
Details on study design:
According to guideline
Irritation parameter:
other: cell viability
Run / experiment:
mean value
Value:
3.4
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
positive indication of irritation
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
In conclusion, it can be stated that in this study and under the experimental conditions reported, Art. 803057 (4-(Dimethylamino)benzaldehyde) possesses an eye irritating potential.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on the available information it is justified to:

- not classify for skin irritation

- classify according to GHS Cat 2 for eye irritation (1)

References:

1. Kolle SN, Kandárová H, Wareing B, van Ravenzwaay B, Landsiedel R. In-house validation of the EpiOcular(TM) eye irritation test and its combination with the bovine corneal opacity and permeability test for the assessment of ocular irritation. Altern Lab Anim. 2011 Sep;39(4):365–87.