Registration Dossier
Registration Dossier
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 943-447-5 | CAS number: -
Endpoint summary
Administrative data
Description of key information
skin irritation (OECD 404): irritating
eye irritation (OECD 492): not irritating; (OECD 437): non-corrosive
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 22 Sep - 14 Oct 1997
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: GLP-Guideline study (reversibility of the effects was observed only up to 7 days after removal of the patches)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Version / remarks:
- 1992
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
- Version / remarks:
- 1992
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- National Board of Health, BronshØj, Denmark
- Species:
- rabbit
- Strain:
- other: Mol:Russian
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: MØllegaard Breeding and Research Centre A/S, Lille Skensved, Denmark
- Weight at study initiation: 2.3-2.5 kg
- Housing: individually in PPO/HIPS cages (2576 cm²) with perforated floor
- Diet: Altromin 2123, pelleted complete rabbit diet (Chr. Petersen, Ringsted, Denmark), ad libitum
- Water: domestic quality drinking water acidified with hydrochloric acid to pH 2.5, ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%): 55±15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12 - Type of coverage:
- semiocclusive
- Preparation of test site:
- clipped
- Vehicle:
- other: 1:1 (w/w) ethanol/diethylphthalate
- Controls:
- other: adjacent areas of skin treated with vehicle served as control
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied: 0.5 mL
- Concentration: 5, 10, 25, 50 and 100% - Duration of treatment / exposure:
- 4 h
- Observation period:
- 7 days
Reading time points: 1, 24, 48 and 72 h - Number of animals:
- 4 females
- Details on study design:
- TEST SITE
- Area of exposure: Appropriate test site on the back (10 cm x 10 cm) divided into two anterior, two centrally and two posterior located test sites. The different test concentrations were applied to the different skin areas simultaneously.
- Type of wrap: The test substance of one of the test concentrations or the vehicle was applied to the skin, using gauze patches of 2.5 cm x 2.5 cm. The patches were secured with 2.5 cm wide adhesive tape and fixed with Scanpor tape (5 cm width). Thereafter Nobifix (6 cm width) was loosely wound round the trunk.
REMOVAL OF TEST SUBSTANCE
- Washing: The skin was cleaned of residual test substance using lukewarm water and mild soap.
- Time after start of exposure: 4 h
SCORING SYSTEM: Draize scoring system - Irritation parameter:
- erythema score
- Basis:
- animal: #1, #2 and #4
- Time point:
- other: mean after 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- no data
- Remarks on result:
- other: test concentration: 100%
- Irritation parameter:
- erythema score
- Basis:
- animal: #3
- Time point:
- other: mean after 24/48/72 h
- Score:
- 2.3
- Max. score:
- 4
- Reversibility:
- no data
- Remarks on result:
- other: test concentration: 100%
- Irritation parameter:
- edema score
- Basis:
- animal: #1, #2 and #4
- Time point:
- other: mean after 24/48/72 h
- Score:
- 1.7
- Max. score:
- 4
- Reversibility:
- no data
- Remarks on result:
- other: test concentration: 100%
- Irritation parameter:
- edema score
- Basis:
- animal: #3
- Time point:
- other: mean after 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- no data
- Remarks on result:
- other: test concentration: 100%
- Irritant / corrosive response data:
- None to well-defined skin reactions were seen at the test sites with 25, 50 and 100% test substance.
None to slight skin reactions were seen at the test sites with vehicle and with 10% test substance. No skin reactions were seen at the test sites with 5% test substance.
On Day 8 scabs were observed in animal No. 1 at the test sites with 25% and 50% test substance, and in animal No. 2 at the test site with 25% test substance.
On Day 8 few scattered scabs were observed in animal No. 1 at the test site with 10% test substance.
On Day 8 crust was observed in animal No. 1 at the test site with 100% test substance and in animal No. 2, 3 and 4 at the test sites with 50% and 100% test substance.
The skin of the other test fields was intact on Day 8. - Interpretation of results:
- irritating
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Under the conditions of this skin irritation study the test substance was irritating to the skin.
Reference
Table 1. Results of the skin irritation study.
Rabbit no. |
Test concentration |
Erythema |
Individual mean values (mean after 24/48/72 h) |
Edema |
Individual mean values (mean after 24/48/72 h) |
|||||||
1 h |
24 h |
48 h |
72 h |
1 h |
24 h |
48 h |
72 h |
|||||
1 |
LA |
100% |
1 |
2 |
2 |
2 |
2.0 |
1 |
1 |
2 |
2 |
1.7 |
RA |
50% |
1 |
2 |
2 |
2 |
2.0 |
1 |
1 |
2 |
2 |
1.7 |
|
LM |
25% |
1 |
2 |
2 |
2 |
2.0 |
1 |
1 |
2 |
2 |
1.7 |
|
RM |
10% |
1 |
1 |
1 |
1 |
1.0 |
1 |
1 |
1 |
1 |
1.0 |
|
LP |
5% |
0 |
0 |
0 |
0 |
0.0 |
0 |
0 |
0 |
0 |
0.0 |
|
RP |
V% |
0 |
0 |
0 |
0 |
0.0 |
0 |
0 |
0 |
0 |
0.0 |
|
2 |
LA |
50% |
1 |
2 |
2 |
2 |
2.0 |
1 |
1 |
2 |
2 |
1.7 |
RA |
25% |
1 |
2 |
2 |
2 |
2.0 |
1 |
1 |
2 |
2 |
1.7 |
|
LM |
10% |
1 |
1 |
1 |
1 |
1.0 |
1 |
1 |
1 |
1 |
1.0 |
|
RM |
5% |
0 |
0 |
0 |
0 |
0.0 |
0 |
0 |
0 |
0 |
0.0 |
|
LP |
V |
0 |
0 |
0 |
0 |
0.0 |
0 |
0 |
0 |
0 |
0.0 |
|
RP |
100% |
1 |
2 |
2 |
2 |
2.0 |
1 |
1 |
2 |
2 |
1.7 |
|
3 |
LA |
25% |
1 |
1 |
2 |
2 |
1.7 |
1 |
1 |
1 |
1 |
1.0 |
RA |
10% |
1 |
1 |
0 |
0 |
0.3 |
1 |
1 |
0 |
0 |
0.3 |
|
LM |
5% |
0 |
0 |
0 |
0 |
0.0 |
0 |
0 |
0 |
0 |
0.0 |
|
RM |
V |
0 |
0 |
0 |
0 |
0.0 |
0 |
0 |
0 |
0 |
0.0 |
|
LP |
100% |
2 |
2 |
2 |
3 |
2.3 |
2 |
2 |
2 |
2 |
2.0 |
|
RP |
50% |
1 |
2 |
2 |
3 |
2.3 |
1 |
1 |
2 |
2 |
1.7 |
|
4 |
LA |
10% |
1 |
1 |
0 |
0 |
0.3 |
1 |
1 |
0 |
0 |
0.3 |
RA |
5% |
0 |
0 |
0 |
0 |
0.0 |
0 |
0 |
0 |
0 |
0.0 |
|
LM |
V |
0 |
1 |
1 |
1 |
1.0 |
0 |
0 |
0 |
0 |
0.0 |
|
RM |
100% |
1 |
2 |
2 |
2 |
2.0 |
1 |
1 |
2 |
2 |
1.7 |
|
LP |
50% |
1 |
2 |
2 |
2 |
2.0 |
1 |
1 |
2 |
2 |
1.7 |
|
RP |
25% |
1 |
2 |
2 |
2 |
2.0 |
1 |
1 |
1 |
1 |
1.0 |
|
LA: Left anterior treatment site
RA: Right anterior treatment site
LM: Left middle treatment site
RM: Right middle treatment site
LP: Left posterior treatment site
RP: Right posterior treatment site
V: Vehicle (1:1 (w/w) ethanol/diethylphthalate)
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 23- 25 Sep 2015
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP-Guideline study
- Qualifier:
- according to guideline
- Guideline:
- other: 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) (2015)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Hess. Ministerium für Umwelt, Klimaschutz, Landwirtschaft und Verbraucherschutz, Wiesbaden, Germany
- Species:
- human
- Strain:
- other: EpiOcular™
- Details on test animals or tissues and environmental conditions:
- TEST MODEL (EpiOcular™ Kit)
- Source: MatTek Corporation, Ashland, USA
- Lot No.: 21572
TEST METHOD
The EpiOcular™ tissue consists of normal, human-derived epidermal keratinocytes which have been cultured to form a stratified squamous epithelium similar to that found in the human cornea. It consists of basal cells which progressively flatten out as the apical surface of the tissue is approached, analogous to the normal in vivo corneal epithelium. Irritant materials are identified by their ability to damage the underlying cell layers which is determined through a decrease in cell viability as determined by MTT reduction.
ADAPTATION TO CELL CULTURE CONDITIONS
1.0 mL assay medium (37 °C) was aliquoted into 6-well plates. The inserts with EpiOcular™ tissues were transferred aseptically into the plates and pre-incubated at standard culture conditions for 1 h. Afterwards, the medium was replaced by 1 mL fresh assay medium and the EpiOcular™ tissues were incubated at standard culture conditions overnight (18 h). After the overnight incubation, the tissues were pre-wetted with 20 µL of Ca²+ Mg²+ free DPBS. The tissues were incubated at standard culture conditions for 30 min.
INCUBATION CONDITIONS (INCUBATOR)
- Temperature (°C): 37 ± 1.5
- CO2 gas concentration (%): 5 ± 0.5
- Humidity (%): 95 - Vehicle:
- unchanged (no vehicle)
- Controls:
- other: The negative control was deionised water and methyl acetate was used as positive control.
- Amount / concentration applied:
- TEST MATERIAL
- Applied volume: 50 µL
POSITIVE SUBSTANCE
- Substance: methyl acetate
- Applied volume: 50 µL
NEGATIVE CONTROL
- Substance: deionised water
- Applied volume: 50 µL - Duration of treatment / exposure:
- 30 min
- Observation period (in vivo):
- not applicable
- Number of animals or in vitro replicates:
- not applicable
The test was performed in duplicate for each treatment and control group. - Details on study design:
- TEST SITE
- Area of exposure: 0.6 cm²
REMOVAL OF TEST SUBSTANCE
- Washing: At the end of the treatment time, the test substance was removed by extensively rinsing the tissues with Ca²+Mg²+ free DPBS in clean beakers.
- Post-treatment incubation period: 2 h
CELL VIABILITY MEASUREMENTS
For determining alterations in cell viability, MTT reduction assays were performed. Therefore, a volume of 300 µL MTT solution was added to each well for 3 h at standard culture conditions. After removal of the MTT solution, wells were rinsed three times with Ca²+Mg²+ free DPBS. Extraction of the formazan product was carried out in 2 mL isopropanol. At the end of the extraction period the optical density (OD) was measured. - Irritation parameter:
- other: cell viability (%)
- Basis:
- other: mean values of 2 tissues
- Time point:
- other: 30 min
- Score:
- 95.1
- Reversibility:
- other: not applicable
- Remarks on result:
- other: Test substance
- Irritation parameter:
- other: cell viability (%)
- Basis:
- other: mean values of 2 tissues
- Time point:
- other: 30 min
- Score:
- 6.9
- Reversibility:
- other: not applicable
- Remarks on result:
- other: Positive control
- Irritation parameter:
- other: cell viability (%)
- Basis:
- other: mean value of 2 tissues
- Time point:
- other: 30 min
- Score:
- 100
- Reversibility:
- other: not applicable
- Remarks on result:
- other: Negative control
- Interpretation of results:
- not irritating
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Under the conditions of the conducted test, the test substance did not exhibit irritating properties towards human-derived epidermal keratinocytes in the EpiOcular TM model.
Reference
Table 1. Results after 30 min incubation time
Test group |
Absorbance* |
Mean absorbance of 2 tissues* |
Rel. absorbance (%)** |
Absolute value of the difference of the rel. absorbance (%) Tissue 1 and 2 |
Rel. absorbance (% of negative control)** |
||
Tissue 1 |
Tissue 2 |
Tissue 1 |
Tissue 2 |
||||
Negative control |
1.568 |
1.653 |
1.611 |
97.4 |
102.6 |
5.3 |
100.0 |
Positive control |
0.107 |
0.114 |
0.110 |
6.6 |
7.1 |
0.5 |
6.9 |
Test substance |
1.459 |
1.606 |
1.533 |
90.6 |
99.7 |
9.1 |
95.1 |
* Mean of two replicate wells after blank correction
** Relative absorbance (rounded values): 100 × (absorbance test substance/positive control) / (absorbance negative control)
The optical pre-experiment (colour interference pre-experiment) to investigate the test substance’s colour change potential in water or isopropanol did not led to a change in colour. Optical evaluation of the MTT-reducing capacity of the test substance with MTT-reagent did not show blue colour. Therefore, additional tests with viable or freeze-killed tissues were not performed.
All acceptance criteria were met.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
There is only one study available.
Justification for selection of eye irritation endpoint:
The reliable GLP compliant OECD Guideline study was chosen.
Effects on skin irritation/corrosion: irritating
Justification for classification or non-classification
The available data on skin irritation meet the criteria for classification as Skin Irrit. Cat. 2 (H315) according to Regulation (EC) 1272/2008.
The available data on eye irritation do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
