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Diss Factsheets

Administrative data

Description of key information

The irritating potential of the substance for skin and eye irritation has been investigated in several in vitro studies, performed according to current OECD guidelines and under GLP regulation.

Based on an in vitro test for skin irritation using a reconstructed human epidermis model (RHE, SkinEthic), the test material is considered to be irritating to the skin (mean viability: 2.53%).

The eye irritating potential of the substance was investigated in a BCOP (IVIS: 18.2; no prediction can be made) and an in vitro test with reconstructed human Cornea-like Epithelium (EpiOcular; viability: 3.3%). Based on the results of these 2 in vitro tests, the substance is considered to be irritating to the eyes.

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:
2011-04-19 to 2011-08-31
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
Qualifier:
according to guideline
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Version / remarks:
Adopted: 22 July 2010
Qualifier:
according to guideline
Guideline:
other: Skinethic skin irritation test -42bis Standard operating procedure (SOP) 2009
GLP compliance:
yes (incl. QA statement)
Specific details on test material used for the study:
Designation: Art. 132720
Synonym: Avodiol
Chem. Name: 1-(4-tert-Butyl-phenyl)-3-(4-methoxy-phenyl)-propane-1,3-diol
CAS-No.: 955359-35-0
Batch: 11/LE/016 K1
Purity: 95.1% (w/w)
Appearance: White, solid
Released until: May 18, 2012
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: SkinEthic Laboratories, Lyon, France)
- Source: human keratinocytes cultured on a polycarbonate filter in conditions which permit their terminal differentiation
- Format: 24 well plate
- Batch: 11 022A 0401


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:
2.53
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:
positive 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:

Negative Control:
The negative control (DPBS-buffer) OD values were 2.274, 2.217 and 2.297 (mean: 2.263, Standard Deviation: 1.80%) and, thus, in the range of ≥1.2 and ≤2.5.

After treatment with the positive control (5% aqueous solution of sodium dodecyl sulfate) the mean relative viability value was 1.02% (standard deviation: 6.01%) and fulfilled the acceptance criteria (<40%)
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  2.263 100 
 Positive Control 42

0.028

1.26

 Test Material

42

0.057

2.53

Interpretation of results:
Category 2 (irritant) based on GHS criteria
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 is considered to be irritating to the skin based on the results of 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 is considered to be irritating to the skin  based on the results of 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:
2016-11-21 to 2017-03-09
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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)
Version / remarks:
28 July 2015
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: MaTTek Corporation: EpiOcular Eye Irritation Test (OCL-200-EIT) for the prediction of acute ocular irritation of chemicals
Version / remarks:
29 Hune 2015
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Specific details on test material used for the study:
Name: Art. 132720 (RonaCare Pristine Bright)
Synonym: Avodiol
CAS-No.: 955359-35-0
Batch: EH16000620
Purity: 95 % (w/w) (HPLC)
Appearance: light cream, free flowing granules
Released until: 2018-06-30


PREPARATION OF THE TEST MATERIAL
The test item Art. 132720 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.
Details on test animals or tissues and environmental conditions:
CELL CULTURE
- Supplier: MatTek Corporation (82105 Bratislava, Slovakia)
- Source: human epidermal keratinocytes cultured to form a stratified squamous epithelium
- Format: 24 well plate
- Batch: 23757


TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment: 37°C
- 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.

Vehicle:
unchanged (no vehicle)
Controls:
yes
yes, concurrent positive control
yes, concurrent negative control
Amount / concentration applied:
TEST ITEM: 50 mg
NEGATIVE CONTROL: 50 µL (deionised water)
POSITIVE CONTROL: 50 µL (methyl acetate)
Duration of treatment / exposure:
6 h
Number of animals or in vitro replicates:
duplicate
Details on study design:
According to guideline
Irritation parameter:
other: cell viability
Run / experiment:
mean value
Value:
3.3
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
positive indication of irritation

 Group Time / [h]  Mean Absorbance  Mean Relative viability / [%]
 Negative Control 6 1.355 100 
 Positive Control 6

0.247

18.2

 Test Item

6

0.044

3.3

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, the test item possesses an eye irritating potential.
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011-06-16 to 2012-01-26
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
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)
GLP compliance:
yes (incl. QA statement)
Specific details on test material used for the study:
Designation: Art. 132720
Synonym: Avodiol
CAS-No.: 955359-35-0
Batch: 11/LE/016K1
Purity: 95.1% (w/w)
Appearance: white solid
Released until: 2012-05-18


PREPARATION OF THE TEST MATERIAL
The test item Art. 132720 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.
Species:
cattle
Strain:
not specified
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: 0431C14
Released until: September 2013

POSITIVE CONTROL: 750 µL

Designation: Art. 814223
Synonym: Imidazole
Supplier: Merck KGaA, Germany
Batch: S5419523
Released until: August 31, 2014
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:
18.2
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: The treatment of the corneas with the negative control (0.9% sodium chloride solution) showed neither an increase of opacity nor an increase of pemeability
- Acceptance criteria met for positive control: After treatment with the positive control (20% Imidazole) the calculated IVIS was 137.4 and, thus, also within two standard deviations of the current historical mean of the positive control (IVIS 81.4 - 151.0). Therefore, the study fulfilled the validity criteria.

Opacity
Permeability
IVIS
per cornea
per group
(mean value)

Negative control
0.9% NaCl Solution
0.375
0.006 0.470
1 .0

0.710
0.005
0.785
1.644
-0.002
1.619
Positive control
20% Imidazole solution
84.301
3.363
134.748
137.4

103.215
2.891
146.576
82.060
3.251
130.832
Test item
Art. 803057
11.398
0.043
12.040
18.2
14.576
0.050
15.327
12.116
1.005
27.187


Interpretation of results:
other: could not be determined
Conclusions:
According to OECD Guideline 437 no prediction on the irritation potential can be made but the test substance does not have to be classified as serious eye irritant (Eye Dam. Cat. 1)
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, no prediction on the irritation potential can be made but the test substance does not have to be classified as serious eye irritant (Eye Dam. Cat. 1)

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

- classify according to GHS Cat 2 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.