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EC number: 701-329-9 | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Skin irritation / corrosion
Administrative data
- Endpoint:
- skin corrosion: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 17 Jul to 20 Sep 2019
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Reference
- Endpoint:
- skin irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 17 Jul to 20 Sep 2019
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
- Version / remarks:
- adopted June 2019
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- OGYÉI, National Institute of Pharmacy and Nutrition, Budapest, Hungary
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Cell source:
- other: EPISKIN™ (SM) (Manufacturer: SkinEthic, France)
- Source strain:
- other: not applicable
- Justification for test system used:
- The EPISKIN™ (SM) model has been validated for corrosivity and irritation testing in an international validation study and its use is recommended by the relevant OECD guidelines for corrosivity and irritation testing (OECD No. 431 and OECD No. 439); therefore, it was considered to be suitable for this study.
- Vehicle:
- unchanged (no vehicle)
- Remarks:
- The test material was applied as supplied
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used:
EPISKIN™ Small/ Human Epidermis (SM/13)
- Tissue batch number:
19-EKIN-029
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure:
room temperature (23.6 - 24.2°C)
- Temperature of post-treatment incubation: 37°C
REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps:
after treatment (3 min, 1 and 4 h, respectively) the tissues were thoroughly rinsed with PBS, residual PBS was removed from the epidermal surface with a pipette without touching the epidermis
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration:
2 mL of 0.3 mg/mL MTT working solution
- Incubation time:
3 hours at 37°C, with 5% CO2, protected from light in a > 95% humidified atmosphere
- Spectrophotometer:
not reported
- Wavelength:
570 nm
- Filter:
not reported
- Filter bandwidth: not reported
- Linear OD range of spectrophotometer:
0.0 to 3.0 OD
FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
EPISKIN™(SM) kits are manufactured according to defined quality assurance procedures (certified ISO 9001). All biological components of the epidermis and the kit culture medium have been tested for the presence of viruses, bacteria and mycoplasma. The quality of the final product is assessed by undertaking a MTT cell viability test and a cytotoxicity test with sodium dodecyl sulphate (SDS). These quality control experiments were conducted at the supplier, SkinEthic laboratories.
- Viability:
The quality of the EpiSkin™ tissue was assessed by undertaking a MTT cell viability test. The IC50 was 1.9 and 2.7 mg/mL for the two batches, respectively (acceptance criteria: 1.5 - 3.0 mg/mL).
- Barrier function:
habe ich nicht gefunden!!!!!!!!
- Morphology:
HES staining revealed multi-layered, highly differentiated epidermis consisting of organized basal, spinous and granular layers, and a multi-layered stratum corneum
- Contamination:
absence of HIV1 and 2 antibodies, hepatitis C antibodies and hepatitis B anitigens was verified from the blood of donors; absence of bacteria, fungus and mycoplasam was verified on cells from donors
NUMBER OF REPLICATE TISSUES:
3 tissues each for the negative control, positive control and both treatment groups, respectively. As the test item was coloured, two additional test item-treated living tissues were used for the non-specific OD evaluation.
CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE
The test substance did not directly reduce MTT.
NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 1
PREDICTION MODEL / DECISION CRITERIA
- The test substance is considered to be irritant to skin if the mean viability of three individual tissues after 15 minutes exposure is less or equal to 50% of the negaitive controls.
- The test substance is considered to be non-corrosive to skin if the mean viability of three individual tissues after 15 minutes exposure is greater than 50% of the negaitive controls. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount applied: 20 mg (10 mg of the test item did not cover the epidermal surface)
VEHICLE
- Amount applied: before application of the test item, 10 µL distilled water was applied to the epidermal surface in order to improve further contact with the epidermal surface
NEGATIVE CONTROL
- Amount applied: 20 µL PBS
POSITIVE CONTROL
- Amount applied: 20 µL
- Concentration: 5% (w/v) SDS - Duration of treatment / exposure:
- 15 min
- Duration of post-treatment incubation (if applicable):
- 42 h at 37°C with 5% CO2 in an > 95% humidified atmosphere
- Number of replicates:
- Test item, negative and positve control: 3 replicates
- Species:
- other: human
- Strain:
- other: EPISKIN™ (SM) (Manufacturer: SkinEthic, France)
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 15 min (mean of three tissues)
- Value:
- 11.3
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- The mean OD value of the three negative control tissues was in the recommended range (0.848) which satisfied the acceptability criterion of being 0.6-1.5. Standard deviation of the viability results for negative control samples was 4.1%.
The positive control treated tissues showed 3.7% viability demonstrating the proper performance of the assay. The standard deviation of the viability results for positive control samples was 0.6%.
The standard deviation of viability values of the three test item-treated tissue samples in the MTT assay was 6.6%.
All these parameters were within acceptable limits and therefore the study was considered to be valid. - Interpretation of results:
- other: CLP/EU GHS criteria met, as the test item is already classified as Skin Corr. 1B according to Regulation (EC) No 1272/2008, no further classification for skin irritation potential is needed
- Conclusions:
- Skin Corr. 1B, based on results of a study according to OECD 431
- Executive summary:
In this reliable and GLP-conform study according to OECD 439, exposure of disks of EPISKINTM
(SM) with the test item for 15 min, resulted in a mean cell viability of 11.3% compared to the negative control. This is below the threshold of 50%, therefore the test item was considered as being irritant to skin.
The experiment met the validity criteria, therefore the study was considered to be valid.
Table 1: Optical Density (OD) and the calculated relative viability %
Substance |
Optical Density (OD) |
Viability |
Standard |
||
|
Measured |
Blank corrected |
(% RV) |
deviation (SD) |
|
Negative Control: |
1 |
0.925 |
0.878 |
103.4 |
-- |
Phosphate buffered saline |
2 |
0.857 |
0.810 |
95.4 |
-- |
|
3 |
0.906 |
0.858 |
101.1 |
-- |
|
mean |
-- |
0.848 |
100.0 |
4.1 |
Positive Control: |
1 |
0.079 |
0.031 |
3.7 |
-- |
5% (w/v) SDS solution |
2 |
0.074 |
0.027 |
3.1 |
-- |
|
3 |
0.085 |
0.037 |
4.4 |
-- |
|
mean |
-- |
0.032 |
3.7 |
0.6 |
Test Item: |
1 |
0.189 |
0.142 |
16.7 |
-- |
Carboxylic Acids, di-, C4-11 |
2 |
0.161 |
0.114 |
13.4 |
-- |
|
3 |
0.081 |
0.033 |
3.9 |
-- |
|
mean |
-- |
0.096 |
11.3 |
6.6 |
Notes:
1. Mean blank value was0.048.
2. Optical density means the mean value of the duplicate wells for each sample (rounded to three decimal places).
3. SDS: sodium dodecyl sulphate (5%(w/v))
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 019
- Report date:
- 2019
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 431 (In Vitro Skin Corrosion: Human Skin Model Test)
- Version / remarks:
- adopted June 2019
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- OGYÉI, National Institute of Pharmacy and Nutrition, Budapest, Hungary
Test material
- Reference substance name:
- Carboxylic acids, di-, C5-9
- EC Number:
- 701-329-9
- Molecular formula:
- C5di: C5H8O4 C6di: C6H10O4 C7di: C7H12O4 C8di: C8H14O4 C9di: C9H16O4
- IUPAC Name:
- Carboxylic acids, di-, C5-9
Constituent 1
In vitro test system
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Cell source:
- other: EPISKIN™ (SM) (Manufacturer: SkinEthic, France)
- Source strain:
- other: not applicable
- Justification for test system used:
- The EPISKIN™ (SM) model has been validated for corrosivity and irritation testing in an international validation study and its use is recommended by the relevant OECD guidelines for corrosivity and irritation testing (OECD No. 431 and OECD No. 439); therefore, it was considered to be suitable for this study.
- Vehicle:
- unchanged (no vehicle)
- Remarks:
- The test material was applied as supplied
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EPISKIN™ Small/ Human Epidermis (SM/13)
- Tissue batch numbers: 19-EKIN-029 used in Experiment I; Batch No.:19-EKIN-038 used in Experiment II
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: room temperature (22.5 - 24.8°C)
- Temperature of post-treatment incubation: 37°C
REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: after treatment (3 min, 1 and 4 h, respectively) the tissues were thoroughly rinsed with PBS, residual PBS was removed from the epidermal surface with a pipette without touching the epidermis
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 2 mL of 0.3 mg/mL MTT working solution
- Incubation time: 3 hours at 37°C, with 5% CO2, protected from light in a > 95% humidified atmosphere
- Spectrophotometer: not reported
- Wavelength: 570 nm
- Filter: not reported
- Filter bandwidth: not reported
- Linear OD range of spectrophotometer: 0.0 to 3.0 OD
FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
EPISKIN™(SM) kits are manufactured according to defined quality assurance procedures (certified ISO 9001). All biological components of the epidermis and the kit culture medium have been tested for the presence of viruses, bacteria and mycoplasma. The quality of the final product is assessed by undertaking a MTT cell viability test and a cytotoxicity test with sodium dodecyl sulphate (SDS). These quality control experiments were conducted at the supplier, SkinEthic laboratories.
- Viability: The quality of the EpiSkin™ tissue was assessed by undertaking a MTT cell viability test. The IC50 was 1.9 and 2.7 mg/mL for the two batches, respectively (acceptance criteria: 1.5 - 3.0 mg/mL).
- Morphology: HES staining revealed multi-layered, highly differentiated epidermis consisting of organized basal, spinous and granular layers, and a multi-layered stratum corneum
- Contamination: absence of HIV1 and 2 antibodies, hepatitis C antibodies and hepatitis B anitigens was verified from the blood of donors; absence of bacteria, fungus and mycoplasam was verified on cells from donors
NUMBER OF REPLICATE TISSUES: 2 tissues each for the negative control, positive control and both treatment groups, respectively. As the test item was coloured, two additional test item-treated living tissues were used for the non-specific OD evaluation in Experiment I (4 hour exposure).
CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE
The test substance did not directly reduce MTT.
NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 2
PREDICTION MODEL / DECISION CRITERIA
- Justification for the selection of the cut-off point(s) if different than recommended in TG 431: The cut-off value of 35% and classification method was validated in an international validation study of this kit (Fentem, 1998).
The test substance is considered to be corrosive to skin if the viability after 3 minutes exposure is less than 35%, or if the viability after 3 minutes exposure is greater than or equal to 35 % and the viability after 1 hour exposure is less than 35%, or if the viability after 1 hour exposure is greater than or equal to 35 % and the viability after 4 hours exposure is less than 35%
- The test substance is considered to be non-corrosive to skin if the viability after 4 hours exposure is greater than or equal to 35%. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount applied: 20 mg
VEHICLE
- Amount applied: after application to the test system, 100 µL physiological saline was added to the test item to ensure good contact with the epidermis
- Lot/batch no.: 90352Y05-2 (B. Braun Pharamceuticals SA)
NEGATIVE CONTROL
- Amount applied: 50 µL 0.9% NaCl
POSITIVE CONTROL
- Amount applied: 50 µL - Duration of treatment / exposure:
- 3 min, 1 h and 4 h
- Number of replicates:
- Test item: 2 replicates per time point (3 min, 1 and 4 h)
Positive control: 2 replicates at 1 and 4 hours
Negative control: 2 replicates per time point (3 min, 1 and 4 h)
Test animals
- Species:
- other: human
- Strain:
- other: EPISKIN™ (SM) (Manufacturer: SkinEthic, France)
Results and discussion
In vitro
Resultsopen allclose all
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 3 min
- Value:
- 84.9
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 1 h
- Value:
- 11
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 4 h
- Value:
- 8.9
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- The mean OD value of the two negative control tissues was in the recommended range (1.089 in Experiment I, and 0.970 and 0.824 in Experiment II for the 3 min and 1 h treatments, respectively) which satisfied the acceptability criterion of being 0.6- 1.5.
The positive control treated tissues showed 1.1% and 0.1% relative viability (Experiment I and II, respectively) when compared to the relevant negative control values, thus demonstrating the proper performance of the assay in each case.
The variability of the calculated viability values of the test item treated replicates were 13.1% (3 min treatment), 22.1% (1 h treatment), and 4.1% (4 h treatment).
The variability of the calculated viability values of the negative control treated replicates were 10.6% (3 min treatment), 0.4% (1 h treatment), and 0.2% (4 h treatment).
All these parameters were within acceptable limits and therefore the study was considered to be valid.
Any other information on results incl. tables
Table 1: Optical Density (OD) and the calculated relative viability % of the samples in Experiment I - (4 hours exposure)
Substance |
Optical Density (OD) |
Viability |
||
|
Measured |
Blank corrected |
(% RV) |
|
Negative Control: |
1 |
1.136 |
1.088 |
99.9 |
Physiological saline |
2 |
1.138 |
1.090 |
100.1 |
(0.9% (w/v) NaCl) |
mean |
-- |
1.089 |
100.0 |
Positive Control: |
1 |
0.053 |
0.006 |
0.5 |
Glacial acetic acid |
2 |
0.067 |
0.019 |
1.7 |
|
mean |
-- |
0.012 |
1.1 |
Test Item: |
1 |
0.146 |
0.099 |
9.0 |
Carboxylic Acids, di-, C4-11 |
2 |
0.142 |
0.095 |
8.7 |
|
mean |
-- |
0.097 |
8.9 |
Table 2: Optical Density (OD) and the calculated relative viability % of the samples in Experiment II (3 min and 3 hours exposure)
Substance |
Optical Density (OD) |
Viability |
||
|
Measured |
Blank corrected |
(% RV) |
|
3 minutes exposure period |
||||
Negative Control: |
1 |
1.069 |
1.022 |
105.3 |
Physiological saline |
2 |
0.966 |
0.919 |
94.7 |
(0.9% (w/v) NaCl) |
mean |
-- |
0.970 |
100.0 |
Test Item: |
1 |
0.817 |
0.770 |
79.3 |
Carboxylic Acids, di-, C4-11 |
2 |
0.925 |
0.877 |
90.4 |
|
mean |
-- |
0.824 |
84.9 |
1 hour exposure period |
||||
Negative Control: |
1 |
0.873 |
0.825 |
100.2 |
Physiological saline |
2 |
0.869 |
0.822 |
99.8 |
(0.9% (w/v) NaCl) |
mean |
-- |
0.824 |
100.0 |
Positive Control: |
1 |
0.050 |
0.002 |
0.3 |
Glacial acetic acid |
2 |
0.047 |
0.000 |
0.0 |
|
mean |
-- |
0.001 |
0.1 |
Test Item: |
1 |
0.128 |
0.080 |
9.8 |
Carboxylic Acids, di-, C4-11 |
2 |
0.148 |
0.100 |
12.2 |
|
mean |
-- |
0.090 |
11.0 |
Applicant's summary and conclusion
- Interpretation of results:
- other: CLP/EU GHS criteria met, classified as Skin Corr. 1B according to Regulation (EC) No 1272/2008
- Conclusions:
- Skin Corr. 1B
- Executive summary:
In this reliable and GLP-conform study according to OECD 431, exposure of disks of EPISKINTM (SM) with the test item for 1 and 4 hours, resulted in mean cell viabilities of 11.0 and 8.9%, repsectively, compared to the negative control. This is below the threshold of 35%, therefore the test item was considered as being corrosive to skin. Exposure of 3 minutes resulted in a mean cell viability of 84.9%. The experiment met the validity criteria, therefore the study was considered to be valid.
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.
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