Registration Dossier

Administrative data

Description of key information

In a reliable in vitro skin corrosion study human skin tissue (eipdermis keratinocytes) was exposed to the substance for 3-minutes and 1-hour. There was 103.1% and 89.2% tissue viability following the 3-minutes and 1-hour exposure points, respectively. Resultantly, the substance is considered to be a non-corrosive to skin.

In an in vitro skin irritation study, human skin tissue (eipdermis keratinocytes) was exposed to the substance for 60-minutes. There was 99.79% tissue viability following the 60-minute exposure point. Resultantly, the substance is considered to be a non-irritant to human skin.

The eye hazard potential of the substance as measured by its ability to induce opacity and increase permeability in an isolated bovine cornea was assessed using the Bovine Corneal Opacity and Permeability test (BCOP test). The substance did not induce ocular irritation through both endpoints (opacity and permeability), resulting in a mean in vitro irritancy score (IVIS) of 19.89 after 4 hours of treatment. In conclusion, since the substance caused an increase of the corneal opacity, no prediction for the damage hazard of the substance to the eye can be made, but the substance is not serious eye damaging (CLP/EPA/GHS (Cat 1).

In a reliable in vitro eye irritation study human reconstructed cornea-like epithelium was exposed to the neat substance for 6 hours. Compared with the value of the negative control, the relative mean absorption value corresponding to the viability of the tissues did not decrease to below 60% (82.4%). Therefore, the substance is not expected to be irritating to eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin corrosion: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
02 November 2017 - 22 December 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 431 (In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method)
Version / remarks:
July 29, 2016
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.40 (In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test (TER))
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
Batch: 1013Q17761
Purity: 100%
Appearance: White powder
Expiry Date: 25 June 2017
Storage Conditions: At room temperature
Test system:
human skin model
Source species:
human
Cell type:
non-transformed keratinocytes
Justification for test system used:
As per OECD Test Guideline.
Vehicle:
water
Control samples:
yes, concurrent vehicle
yes, concurrent positive control
Amount/concentration applied:
25 μL of deionised water and 25 ± 2mg (39.7 mg/cm2 according to guideline) of the test item.
Each 50 μL were applied to each set of duplicate tissues.
Duration of treatment / exposure:
• Test Item: 3 ± 0.5 minutes, 60 ± 5 minutes
• Negative Control: 3 ± 0.5 minutes, 60 ± 5 minutes
• Positive Control: 3 ± 0.5 minutes, 60 ± 5 minutes
Duration of post-treatment incubation (if applicable):
3 hour post-treatment incubation period
Number of replicates:
Duplicate.
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
3 minute
Value:
103.1
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
60 minutes
Value:
89.2
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Other effects / acceptance of results:
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: the mean OD of the tissue replicates treated with the negative control is ≥ 0.8 and ≤ 2.8 for every exposure time (range: 1.535 to 1.700)
- Acceptance criteria met for positive control: the mean viability of the tissue replicates treated with the positive control for 1 hour, is <15% compared to the negative control (2.4%)
- Acceptance criteria met for variability between replicate measurements: the Coefficient of Variation (CV) in the range 20 – 100% viability between tissue replicates is ≤ 30% (range: 0.4% to 5.4%)
Interpretation of results:
GHS criteria not met
Conclusions:
The substance is considered to be a non-corrosive to skin.
Executive summary:

In an in vitro skin corrosion study human skin tissue (eipdermis keratinocytes) was exposed to the substance for 3-minutes and 1-hour. There was 103.1% and 89.2% tissue viability following the 3-minutes and 1-hour exposure points, respectively. Resultantly, the substance is considered to be a non-corrosive to skin.

Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
06 June 2018 - 22 June 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Version / remarks:
July 28, 2015
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
Batch: 1013Q17761
Purity: 100%
Appearance: White powder
Expiry Date: 25 June 2018
Storage Conditions: At room temperature
Test system:
human skin model
Source species:
human
Cell type:
non-transformed keratinocytes
Vehicle:
other: DPBS
Remarks:
Area wetted with 25 μL DPBS prior to application.
Control samples:
yes, concurrent vehicle
yes, concurrent positive control
Amount/concentration applied:
Approximately 25 mg (~ 39 mg/cm2 according to guideline).
Duration of treatment / exposure:
60 minutes
Number of replicates:
Triplicate.
Irritation / corrosion parameter:
% tissue viability
Value:
99.79
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid
Remarks on result:
no indication of irritation

 Treatment Group  Mean Rel. Viability
 Negative control  100
 Positive control  2.76
 Substance  99.79
Interpretation of results:
GHS criteria not met
Conclusions:
The substance was not an skin irritant under hte conditions of this study.
Executive summary:

In an in vitro skin irritation study, human skin tissue (eipdermis keratinocytes) was exposed to the substance for 60-minutes. There was 99.79% tissue viability following the 60-minute exposure point. Resultantly, the substance is considered to be a non-irritant to human skin.

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:
21 November 2017 - 21 November 2017
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 i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)
Version / remarks:
July, 2013
Deviations:
no
Qualifier:
according to
Guideline:
EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
Batch: 1013Q17761
Purity: 100%
Appearance: White powder
Expiry Date: 25 June 2017
Storage Conditions: At room temperature
Species:
cattle
Details on test animals or tissues and environmental conditions:
Freshly isolated bovine cornea (at least 9 month old donor cattle).
Vehicle:
physiological saline
Remarks:
20% suspension (w/v)
Controls:
yes, concurrent vehicle
yes, concurrent positive control
Amount / concentration applied:
0.75 mL each on the surface of the corneae
Duration of treatment / exposure:
240 minutes
Number of animals or in vitro replicates:
Triplicate
Irritation parameter:
in vitro irritation score
Value:
19.89
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Other effects / acceptance of results:
For the negative control (saline) neither an increase of opacity nor permeability of the corneae could be observed (mean IVIS = 1.00).
The positive control (10% (w/v) Benzalkonium chloride in saline) showed clear opacity and distinctive permeability of the corneae (mean IVIS =138.03) corresponding to a classification as serious eye damaging (CLP/EPA/GHS (Cat 1)).
Interpretation of results:
study cannot be used for classification
Conclusions:
According to OECD 437 no prediction for the damage hazard of the substance to the eye can be made, but the substance is not serious eye damaging (CLP/EPA/GHS (Cat 1).
Executive summary:

The eye hazard potential of the substance as measured by its ability to induce opacity and increase permeability in an isolated bovine cornea was assessed using the Bovine Corneal Opacity and Permeability test (BCOP test). The eye damage of the substance was tested through topical application for approximately 240 minutes.  The substance did not induce ocular irritation through both endpoints (opacity and permeability), resulting in a mean in vitro irritancy score (IVIS) of 19.89 after 4 hours of treatment. In conclusion, since the substance caused an increase of the corneal opacity, according to OECD 437, no prediction for the damage hazard of the substance to the eye can be made, but the substance is not serious eye damaging (CLP/EPA/GHS (Cat 1).

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 January 2018 - 18 January 2018
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)
Version / remarks:
9th October 2017
Deviations:
yes
Remarks:
The pre-test incubation period is 3 h ± 15 min for the substance in water. The substance was only incubated for 1 hour. This deviation has no impact on the outcome of the study since the supplier protocol recommends “at least 1 hour”.
GLP compliance:
yes
Specific details on test material used for the study:
Batch: 1013Q17761
Purity: 100%
Appearance: White powder
Expiry Date: 25 June 2018
Storage Conditions: At room temperature
Species:
human
Details on test animals or tissues and environmental conditions:
Human-derived epidermal keratinocytes.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent positive control
yes, concurrent negative control
Amount / concentration applied:
Substance: 50 mg
Controls: 50 µL
Duration of treatment / exposure:
6 hours
Number of animals or in vitro replicates:
Duplicate
Irritation parameter:
in vitro irritation score
Value:
82.4
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Other effects / acceptance of results:
• The negative control OD is > 0.8 and < 2.5 (1.580 and 1.683).
• The mean relative viability of the positive control is below 50% of the negative control viability (28.3%).
• The difference of viability between the two relating tissues of a single item is < 20% (values between 2.1% and 4.2%) in the same run (for positive and negative control tissues and tissues of single test items).
Treatment with the positive control induced a decrease in the mean relative absorbance compared with the negative control to 28.3%, thus the validity of the test system is ensured.

Results after treatment for 6 hours with the substance and the controls

 Treatment Group Tissue No.   

Mean OD

of 2 Wells blank corrrected

 

Mean

OD

of Treatment Group blank corrected

  

Rel. Viability [%] Tissue
1, 2

Absolute Value of the Difference of Rel. Viability 
Tissue 1,2
[%]
 

Mean Rel. Viability

[%]

 Negative Control

 1

 1.616

 1.583

 102.1

 4.2

 100.0

 

 2

 1.550

 

 97.9

 

 

 Positive Control

 1

 0.426

 0.448

 26.9

 2.9

 28.3

 

 2

 0.471

 

 29.8

 

 

 Test Item

 1

 1.321

 1.304

 83.4

 2.1

 82.4

 

 2

 1.287

 

 81.3

 

 

Interpretation of results:
GHS criteria not met
Conclusions:
The substance is not expected to be irritating to eyes.
Executive summary:

In an in vitro eye irritation study human reconstructed cornea-like epithelium was exposed to the neat substance for 6 hours. Compared with the value of the negative control, the relative mean absorption value corresponding to the viability of the tissues did not decrease to below 60% (82.4%). Therefore, the substance is not expected to be irritating to eyes.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on the findings of reliable in vitro skin corrosion and irritation studies conducted on the substance, classification of the substance is not justified.

Based on the findings of a reliable in vitro eye irritation study conducted on the substance, classification of the substance is not justified.