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EC number: 231-007-9 | CAS number: 7403-42-1
- 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
Endpoint summary
Administrative data
Description of key information
Skin irritation/corrosion (OECD 439 and OECD 431): irritating
Eye irritation (OECD 437): not irritating
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 13 Feb - 02 Jun 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
- Version / remarks:
- adopted 28 Jul 2015
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
- Version / remarks:
- Commission Regulation No 440/2008 of 30 May 2008, 1st ATP of 23 Jul 2009
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Hess. Ministerium für Umwelt, Klimaschutz, Landwirtschaft und Verbraucherschutz, Wiesbaden, Germany
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Cell source:
- other: EpiDerm™
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EpiDerm™ (MatTek Corporation, Bratislava, Slovakia)
- Tissue batch number: 23395
- Delivery date: 31 May 2016
- Date of initiation of testing: 21 Feb 2017
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 37 ± 1.5 °C for 35 min in the incubator; thereafter at room temperature for 25 min in a sterile bench
REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: Tissues were gently rinsed with DPBS at least 15 times in order to remove any residual test material. After the rinsing the inserts were submerged in DPBS at least 3 times. Afterwards the inserts were once again rinsed with DPBS from the inside and the outside.
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 1 mg/mL
- Incubation time: 3 h
- Spectrophotometer: microplate reader (Versamax, Molecular Devices, Softmax Pro v.4.7.1)
- Wavelength: 570 nm
FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
- Viability: The quality of the EpiDerm™ tissue was assessed by undertaking an MTT cell viability test. The determined OD (540 - 570 nm) was 1.211 ± 0.175 (acceptance criteria: 1.0 - 3.0).
- Barrier function: The barrier function was assessed by determination of the exposure time required to reduce tissue viability by 50% (ET-50) upon application of 100 µL of 1% Triton X-100. The ET-50 value was determined to be 4.83 h (acceptance criteria: 4.77-8.72 h).
- Contamination: The cells used to produce the EpiDerm™ tissue were screened for the presence of viruses, bacteria, yeast and other fungi.
NUMBER OF REPLICATE TISSUES: 3
CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE
Since the test substance did not directly reduce MTT, an additional test with freeze-killed tissues was not performed.
NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: single experiment
PREDICTION MODEL / DECISION CRITERIA
- The test substance is considered to be irritant to skin if the viability after 1 hour exposure is less or equal than 50%. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount applied: 30 µL
NEGATIVE CONTROL
- Amount applied: 30 µL
POSITIVE CONTROL
- Amount applied: 30 µL
- Concentration: 5% aqueous solution - Duration of treatment / exposure:
- 60 min
- Duration of post-treatment incubation (if applicable):
- approximately 42 h
- Number of replicates:
- triplicates for each treatment and control group
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 60 min
- Value:
- 15.7
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- OTHER EFFECTS:
- Direct-MTT reduction: The test substance was not considered to be a MTT reducer.
- Colour interference with MTT: The test substance did not change colour when mixed with deionised water. Also its intrinsic colour was not intensive.
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: The negative control OD (1.978, 1.710 and 1.638) was in the range of the required acceptability criterion of mean OD ≥ 0.8 and ≤ 2.8 for the 60 min treatment interval thus showing the quality of the tissues.
- Acceptance criteria met for positive control: Exposure to the positive control induced a decrease in the relative absorbance to 3.1% as compared to the negative control thus confirming the validity of the test system.
- Acceptance criteria met for variability between replicate measurements: The relative standard deviations of the 3 identical replicates of the test substance and negative control in the main test were below 10.4% (threshold of OECD 439: <18%). - Interpretation of results:
- other: irritating potential (Skin Irrit. 2 or Skin Corr. 1 according to Regulation (EC) No 1272/2008)
- Conclusions:
- Under the conditions of the conducted test, the test substance possessed irritating properties towards reconstructed human epidermis tissue in the EpiDerm™ model.
- Executive summary:
The skin irritation potential of the test substance was determined by an in vitro skin irritation test using a reconstructed human skin model according to OECD Guideline 439 and in compliance with GLP (2017). After treatment with the test substance for 60 min the tissue viability decreased to 15.7% compared to the negative control (threshold for irritancy≤50%).Therefore, the test substance is considered to possess an irritant potential towards human-derived epidermal keratinocytes.
- Endpoint:
- skin corrosion: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 07 - 21 Apr 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 431 (In Vitro Skin Corrosion: Human Skin Model Test)
- Version / remarks:
- adopted 29 Jul 2016
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: EU B.40 bis (In Vitro Skin Corrosion: Human Skin Model Test)
- Version / remarks:
- Commission Regulation (EC) No 440/2008 of 30 May 2008
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Hess. Ministerium für Umwelt, Klimaschutz, Landwirtschaft und Verbraucherschutz, Wiesbaden, Germany
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Cell source:
- other: EpiDerm™ (EPI-200)
- Source strain:
- not specified
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE)
- Model used: EpiDerm™ (EPI-200) (MatTek Corporation, Bratislava, Slovakia)
- Tissue batch number: 25806
- Delivery date: 19 Apr 2017
- Date of initiation of testing: 19 Apr 2017
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: room temperature (3 ± 0.5 min exposure), 37 ± 1.5 °C (60 ± 5 min exposure)
REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: Tissues were gently rinsed with DPBS (20 times) in order to remove any residual test material.
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 1 mg/mL
- Incubation time: 3 h
- Spectrophotometer: microplate reader (Versamax, Molecular Devices, SoftMax Pro Enterprise v.4.7.1)
- Wavelength: 570 nm
- Filter: without reference filter
FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
- Viability: The quality of the EpiDerm™ tissue was assessed by an MTT cell viability test. The determined OD (540 - 570 nm) was 1.581 ± 0.238 (acceptance criteria: 1.0 - 3.0).
- Barrier function: The barrier function was assessed by determination of the exposure time required to reduce tissue viability by 50% (ET-50) upon application of 100 µL of 1% Triton X-100. The ET-50 value was determined to be 5.58 h (acceptance criteria: 4.77-8.72 h).
- Contamination: The cells used to produce the EpiDerm™ tissue were screened for the presence of viruses, bacteria, yeast and other fungi.
NUMBER OF REPLICATE TISSUES: 2
CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE
Since the test substance did not directly reduce the MTT solution, an additional functional check was not performed.
NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: single experiment
PREDICTION MODEL / DECISION CRITERIA
- The test substance is considered to be non-corrosive to skin if the viability after 3 minutes exposure is greater or equal than 50% and the viability after 1 hour exposure is greater or equal than 15%.
- The test substance is considered to be corrosive to skin if the viability after 3 minutes exposure is less than 50%, or if the viability after 3 minutes exposure is greater than or equal to 50% and the viability after 1 hour exposure is less than 15%. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount applied: 50 µL
NEGATIVE CONTROL
- Amount applied: 50 µL
POSITIVE CONTROL
- Amount applied: 50 µL
- Concentration: 8 N - Duration of treatment / exposure:
- 3 ± 0.5 min and 60 ± 5 min
- Number of replicates:
- duplicates for each treatment and control group
- Irritation / corrosion parameter:
- % tissue viability
- Remarks:
- mean value of 2 tissues
- Run / experiment:
- 3 min exposure
- Value:
- 109.8
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation / corrosion parameter:
- % tissue viability
- Remarks:
- mean value of 2 tissues
- Run / experiment:
- 60 min exposure
- Value:
- 114.1
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- OTHER EFFECTS
- Direct-MTT reduction: Since the test substance did not directly reduce MTT, an additional test with freeze-killed or viable tissues was not performed.
- Colour interference with MTT: The test substance did not change colour, when mixed with deionised water and thus passed the colour interference pre-test.
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: The mean OD of the tissue replicates treated with the negative control was ≥ 0.8 and ≤ 2.8 for every exposure time (values between 1.559 and 1.661).
- Acceptance criteria met for positive control: The mean viability of the tissue replicates treated with the positive control for 1 hour was <15% compared to the negative control (9.6%).
- Acceptance criteria met for variability between replicate measurements: The coefficient of variation (CV) in the range 20 – 100% viability between tissue replicates is ≤ 30% (values between 0.6% and 9.7%). - Interpretation of results:
- other: non-corrosive according to Regulation (EC) No 1272/2008
- Conclusions:
- Under the conditions of the conducted test, the test substance did not possess corrosive properties towards reconstructed human epidermis tissue in the EpiDerm™ model.
- Executive summary:
The skin corrosion potential of the test substance was investigated by an in vitro skin corrosion test using a human skin model according to OECD Guideline 431 and in compliance with GLP (2017). After treatment with the test substance the tissue viability did not decrease (3 min exposure: 109.8%; 1 h exposure:114.1%) compared to the negative control. Therefore, the test substance is not considered to be corrosive towards human-derived epidermal keratinocytes.
Referenceopen allclose all
Table 2. Results after treatment with the test substance and controls
Test group |
Mean absorbance at 570 nm* |
Rel. absorbance (%)** |
Rel. SD (%) |
Rel. absorbance (% of negative control)*** |
||||
Tissue 1 |
Tissue 2 |
Tissue 3 |
Tissue 1 |
Tissue 2 |
Tissue 3 |
|||
Negative control |
1.978 |
1.710 |
1.638 |
111.4 |
96.3 |
92.3 |
10.1 |
100.0 |
Positive control |
0.057 |
0.056 |
0.053 |
3.2 |
3.1 |
3.0 |
4.1 |
3.1 |
Test substance |
0.312 |
0.264 |
0.260 |
17.6 |
14.9 |
14.7 |
10.4 |
15.7 |
* Mean of three replicate wells after blank correction (blank = 0.036)
** Relative absorbance per tissue (rounded values): 100 × (absorbance tissue) / (mean absorbance negative control)
*** Relative absorbance per treatment group (rounded values): 100 × (mean absorbance test substance/positive control) / (mean absorbance negative control)
Table 2. Results after treatment with the test substance and controls
|
Exposure interval (min) |
Aborbance at 570 nm * |
Mean absorbance of 2 tissues |
Absorbance (% of negative control) ** |
CV (%) |
Rel. absorbance (% of negative control) ** |
||
Tissue 1 |
Tissue 2 |
Tissue 1 |
Tissue 2 |
|||||
Negative control |
3 |
1.522 |
1.586 |
1.554 |
97.9 |
102.1 |
2.9 |
100.0 |
Positive control |
0.348 |
0.399 |
0.373 |
22.4 |
25.7 |
9.7 |
24.0 |
|
Test substance |
1.681 |
1.731 |
1.706 |
108.1 |
111.4 |
2.1 |
109.8 |
|
Negative control |
60 |
1.624 |
1.555 |
1.590 |
102.2 |
97.8 |
3.1 |
100.0 |
Positive control |
0.154 |
0.151 |
0.153 |
9.7 |
9.5 |
1.2 |
9.6 |
|
Test substance |
1.807 |
1.822 |
1.814 |
113.7 |
114.6 |
0.6 |
114.1 |
* Mean of three replicate wells after blank correction (blank: 0.037)
** Relative absorbance (rounded values): 100 × (mean absorbance test substance/positive control) / (mean absorbance negative control)
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:
- 20 Feb 2017
- 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 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
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Hess. Ministerium für Umwelt, Klimaschutz, Landwirtschaft und Verbraucherschutz, Wiesbaden, Germany
- Species:
- cattle
- Strain:
- not specified
- Details on test animals or tissues and environmental conditions:
- SOURCE OF COLLECTED EYES
- Source: Schlachthof Aschaffenburg, 63739 Aschaffenburg, Germany
- Characteristics of donor animals: at least 9 month old
- Storage, temperature and transport conditions of ocular tissue: The isolated eyes were transported in Hank's Buffered Salt Solution (HBSS) containing 1% (v/v) Penicillin/Streptomycin (100 units/mL, respectively).
- Time interval prior to initiating testing: The corneae were isolated on the same day after delivery of the eyes and directly used in the BCOP test.
- Indication of any existing defects or lesions in ocular tissue samples: All eyes were carefully examined macroscopically for defects. Those presenting defects such as vascularization, pigmentation, opacity and scratches were discarded. - Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent positive control
- yes, concurrent negative control
- Amount / concentration applied:
- TEST MATERIAL
- Amount applied: 0.75 mL
POSITIVE CONTROL
- Amount applied: 0.75 mL
NEGATIVE CONTROL
- Amount applied: 0.75 mL - Duration of treatment / exposure:
- 10 min at 32 ± 1 °C
- Duration of post- treatment incubation (in vitro):
- 2 h
- Number of animals or in vitro replicates:
- triplicates for each treatment and control group
- Irritation parameter:
- in vitro irritation score
- Remarks:
- mean value of 3 cornea
- Run / experiment:
- 10 min exposure
- Value:
- 0.18
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- With the negative control (0.9% (w/v) NaCl solution in deionised water) neither an increase of opacity nor permeability of the corneae could be observed.
The positive control (2-ethoxyethanol) showed clear opacity and distinctive permeability of the corneae (mean IVIS = 79.74) corresponding to a classification as serious eye damaging.
Relative to the negative control, the test substance did not cause an increase in corneal opacity or permeability (mean IVIS = 0.18).
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: The negative control resulted in opacity and permeability values that were less than the established upper limits for background opacity and permeability values for bovine corneae treated with the respective negative control.
- Acceptance criteria met for postive control: The positive control resulted in an IVIS which was within two standard deviations of the current historical mean. - Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
- Conclusions:
- Under conditions of the Bovine Corneal Opacity and Permeability Test (BCOP) the test subtance was not irritating to the eye.
- Executive summary:
The eye irritation potential of the test substance was determined by a bovine corneal opacity and permeability (BCOP) test according to OECD Guideline 437 and in compliance with GLP (2017). Application of the test substance to bovine corneae resulted in a calculated mean IVIS of 0.18. Thus, the test substance is not considered to be irritant to the eye.
Reference
Table 2. Results after 10 min incubation time.
Test group |
Opacity value = Difference (t130-t0) of Opacity |
Permeability at 490 nm (OD490) |
IVIS |
Mean IVIS |
||
|
|
Mean |
|
Mean |
||
Negative Control |
0 |
0.00 |
0.064 |
0.061 |
0.96 |
0.92 |
0 |
0.061 |
0.92 |
||||
0 |
0.058 |
0.87 |
||||
Positive Control |
61.0* |
1.072* |
77.08 |
79.74 |
||
60.0* |
0.957* |
74.36 |
||||
66.0* |
1.452* |
87.78 |
||||
Test substance |
0.00* |
0.007* |
0.11 |
0.18 |
||
0.00* |
0.021* |
0.32 |
||||
0.00* |
0.008* |
0.12 |
* Corrected values
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Skin
The skin irritation potential of the test substance was determined by an in vitro skin irritation test using a reconstructed human skin model according to OECD Guideline 439 and in compliance with GLP (2017). After treatment with the test substance for 60 min the tissue viability decreased to 15.7% compared to the negative control (threshold for irritancy ≤ 50%).Therefore, the test substance is considered to possess an irritant potential towards human-derived epidermal keratinocytes.
In a next step, the skin corrosion potential of the test substance was investigated by an in vitro skin corrosion test using a human skin model according to OECD Guideline 431 and in compliance with GLP (2017). After treatment with the test substance the tissue viability did not decrease (3 min exposure: 109.8%; 1 h exposure: 114.1%) compared to the negative control. Therefore, the test substance is not considered to be corrosive towards human-derived epidermal keratinocytes.
In conclusion, based on the available data on skin irritation/corrosion, the test substance is considered to be irritating to skin and therefore classified as Skin Irrit. 2 (H315) according to CLP.
Eye
The eye irritation potential of the test substance was determined by a bovine corneal opacity and permeability (BCOP) test according to OECD Guideline 437 and in compliance with GLP (2017). Application of the test substance to bovine corneae resulted in a calculated mean IVIS of 0.18. Thus, the test substance is not considered to be irritant to the eye.
Justification for classification or non-classification
The available data on skin irritation meet the criteria for classification as Skin Irrit. 2 (H315) according to Regulation (EC) 1272/2008.
The available data on eye irritation do not met 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.