Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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.
Diss Factsheets
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: 238-692-3 | CAS number: 14643-87-9
- 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
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin corrosion: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From January 22, 2018 to January 25, 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 431 (In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method)
- Version / remarks:
- Adopted Jul. 29, 2016
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.40 (In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test (TER))
- Version / remarks:
- Dated May 30, 2008
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test system:
- other: EpiDermTM Kit (EPI-212-SCT; Batch# 25875)
- Source species:
- other: Human-derived
- Cell type:
- other: Human-derived epidermal keratinocytes which have been cultured to form a multi-layered, highly differentiated model of the human epidermis.
- Cell source:
- other: Supplier: MatTek In Vitro Life Science Laboratories, Bratislava.
- Source strain:
- not specified
- Justification for test system used:
- The test system consists of organized basal, spinous and granular layers, and a multi-layered stratum corneum containing intercellular lamellar lipid layers arranged in patterns analogous to those found in vivo.
- Vehicle:
- water
- Remarks:
- Demineralised water, prepared by LAUS GmbH, from an ion-exchanger, batch no: 20170815.
- Details on test system:
- - Environmental Condition during incubation / exposure:
37 ± 1°C and 5.0 ± 0.5% CO2
- Amount of test substance applied: 26.0 and 26.1 mg (3 minutes exposure); 26.6 mg (1 h exposure) - Control samples:
- yes, concurrent vehicle
- yes, concurrent positive control
- Amount/concentration applied:
- 3 minutes exposure: 26.0 mg (Tissue 1); 26.1 mg (Tissue 2)
1 h exposure: 26.6 mg (Tissue 1 and 2) - Duration of treatment / exposure:
- 3 minutes exposure
1 h exposure - Number of replicates:
- 2
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 3 minutes treatment
- Value:
- ca. 72.5
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: Inconclusive, to be determined based on 1 h reading
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 1 h treatment
- Value:
- ca. 10.7
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- positive indication of irritation
- Other effects / acceptance of results:
- All Validity criteria for the Experiment were met:
1. The criterion for optical density of the negative control (≥ 0.8 and ≤ 2.8) was fulfilled: optical density was 2.1 (3 minutes); 2.0 (1 h).
2. The positive control showed clear corrosive effects. The criterion for the viability of the 1 h experiment, expressed as % of the negative control (< 15%), was fulfilled, too. The mean value of relative tissue viability was 9.9%.
3. Values for negative control and for positive control were within the range of historical data of the test facility - Interpretation of results:
- Category 1 (corrosive) based on GHS criteria
- Conclusions:
- Under the study conditions, the test substance was considered as corrosive to skin.
- Executive summary:
A study was conducted to determine skin corrosion potential of the test substance using the reconstructed human epidermis (RHE) test method according to OECD Guideline 431, in compliance with GLP. Two tissues of the human skin model EpiDermTM were treated with the test substance for 3 min and 1 h, respectively. Demineralised water was used as negative control and potassium hydroxide (8M) was used as positive control. After treatment, the respective substance was rinsed from the tissues. Then, cell viability of the tissues was evaluated by MTT, which can be reduced to a blue formazan. Formazan production was evaluated by measuring the optical density (OD) of the resulting solution. After treatment with the test substance, the mean value of relative tissue viability was reduced to 72.5% (3 min exposure) and 10.7% (1 h exposure), which qualifies as corrosive. Under the study conditions, the test substance was therefore considered as corrosive to skin (Andres, 2018).
Reference
The mean value of relative tissue viability of the test substance was reduced to 72.5% after 3 minutes treatment. Per criteria for assessment of corrosivity, this value is above the threshold for corrosively (50%). After 1 h treatment, the mean value of relative tissue viability of the test substance was reduced to 10.7%, lying below the threshold for corrosively (15%). Therefore, the test substance is considered as corrosive to skin.
The values of the negative control met the required acceptability criterion of mean OD ≥ 0.8 and ≤ 2.8 for both treatment intervals, thus showing the quality of the tissues. The positive control has met the validity criterion too, thus ensuring the validity of the test system.
Absorbance values blank isopropanol (OD 570 nm) | |||||||
Replicate | 1 | 2 | 3 | 4 | 5 | 6 | Mean |
Absorbance | 0.039 | 0.038 | 0.039 | 0.04 | 0.038 | 0.038 | 0.039 |
Replicate | 7 | 8 | 9 | 10 | 11 | 12 | |
Absorbance | 0.04 | 0.038 | 0.043 | 0.038 | 0.039 | 0.038 |
Absorbance values (OD 570 nm) of negative control, test substance and positive control | ||||||
Incubation | Negative Control | Test substance | Positive Control | |||
Tissue 1 | Tissue 2 | Tissue 1 | Tissue 2 | Tissue 1 | Tissue 2 | |
3 min | 2.125 | 2.117 | 1.456 | 1.576 | 0.404 | 0.447 |
2.115 | 2.09 | 1.527 | 1.587 | 0.427 | 0.446 | |
2.147 | 2.093 | 1.527 | 1.593 | 0.423 | 0.446 | |
1 h | 2 | 1.974 | 0.25 | 0.248 | 0.26 | 0.224 |
2.093 | 2.009 | 0.259 | 0.25 | 0.244 | 0.221 | |
2.116 | 1.988 | 0.259 | 0.251 | 0.246 | 0.225 |
Mean Absorbance Values of the 3 Minutes Experiment | |||
Designation | Negative Control | Test substance | Positive Control |
Mean – blank (tissue 1) | 2.09 | 1.464 | 0.379 |
Mean – blank (tissue 2) | 2.061 | 1.546 | 0.407 |
Mean of the two tissues | 2.076 | 1.505 | 0.393 |
RSD | 1.00% | 3.90% | 5.10% |
Mean Absorbance Values of the 1 h Experiment | |||
Designation | Negative Control | Test substance | Positive Control |
Mean – blank (tissue 1) | 2.031 | 0.217 | 0.211 |
Mean – blank (tissue 2) | 1.951 | 0.211 | 0.184 |
Mean of the two tissues | 1.991 | 0.214 | 0.198 |
RSD | 2.80% | 2.10% | 9.50% |
Comparison of Tissue Viability | ||
Incubation | Positive Control | Test substance |
3 min | 18.90% | 72.50% |
1 h | 9.90% | 10.70% |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (corrosive)
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:
- From Dec. 07, 2017 to Dec. 07, 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:
- Oct. 09, 2017
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: OECD Guideline for the Testing of Chemicals, Series on Testing and Assessment No. 160
- Version / remarks:
- “Guidance Document On “The Bovine Corneal Opacity and Permeability (BCOP) and Isolated Chicken Eye (Ice) Test Methods: Collection of Tissues for Histological Evaluation and Collection of Data on Non-Severe Irritants”; 25. Oct. 2011
- 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)
- Version / remarks:
- Feb. 14, 2017
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Species:
- cattle
- Strain:
- other: Bos primigenius Taurus (fresh bovine corneas)
- Details on test animals or tissues and environmental conditions:
- Test System: Bos primigenius Taurus (fresh bovine corneas). Fresh bovine eyes were obtained from the slaughterhouse Müller Fleisch GmbH, Enzstr. 2-4, 75217 Birkenfeld, Germany, on the Day of the test. The cattle were between 12 and 60 months old. The eyes were transported to the test facility in Hanks’ Balanced Salt Solution with 1% Penicillin-Streptomycin solution (Penicillin 100 U/mL, Streptomycin 100 µg/mL) in a suitable cooled container. After the arrival of the corneas, they were examined and only corneas which were free from damages were used. The corneas were excised with a scalpel and cut from the globe with a 2-3 mm ring of sclera around the outside. Each cornea was transferred to a cornea holder in which pre-warmed cMEM (32 ± 1°C) without phenol red was filled. The holders were then incubated for 1 h in the incubation chamber at 32 ± 1°C.
- Vehicle:
- Hank's balanced salt solution
- Remarks:
- Batch no.: 20171207, 10-fold concentrated, diluted in demineralised water (1:10)
- Controls:
- yes, concurrent positive control
- yes, concurrent negative control
- Amount / concentration applied:
- Test substance Preparation: The test substance was a solid non-surface-active substance. It was tested as a suspension with a concentration of 20% in HBSS. The suspension was prepared freshly on the Day of the assay.
- Duration of treatment / exposure:
- Incubation time: 4 h
- Number of animals or in vitro replicates:
- For each treatment group [negative control solution (HBSS), test substance and positive control (20% imidazole solution)], three replicates were used.
- Details on study design:
- OPACITY TEST
After the initial incubation, the medium was changed and the baseline opacity for each cornea was recorded. After removal of the pre-incubation medium (cMEM without phenol red), 750 µL negative control solution, test substance suspension and positive control solution were applied to each replicate. The test or control preparations were given directly on the epithelium in such a manner that as much as possible of the cornea was covered with test or control substances. Exposure time on the corneas was 4 h at 32 ± 1°C. After thorough rinsing with cMEM with phenol red and final rinsing with cMEM without phenol red, both chambers were filled with cMEM without phenol red, and the final opacity value of each cornea was recorded.
PERMEABILITY TEST
After the recording of the final opacity value, the cMEM without phenol red was removed from the front chamber, and 1 mL sodium fluorescein solution was added to the front chamber for the detection of permeability of the corneas. For the open chamber method, a sodium fluorescein solution with a concentration of 5 mg/mL was used. The chambers were then closed again and incubated for 90 min. at 32 ± 1°C. After incubation, the content of the posterior chamber was thoroughly mixed. Then, its optical density at 492 nm was measured with the microtiter plate photometer. - Irritation parameter:
- in vitro irritation score
- Run / experiment:
- Mean of three replicates
- Value:
- ca. 121.95
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- positive indication of irritation
- Remarks:
- Relative Standard Deviation IVIS: 7.22%; The test substance induced serious eye damage on the cornea of the bovine eye.
- Other effects / acceptance of results:
- In the negative control, no signs of eye irritation were observed. The positive control induced serious eye damage, which would be classified as GHS category I.
- Interpretation of results:
- Category 1 (irreversible effects on the eye) based on GHS criteria
- Conclusions:
- Under study conditions, the test substance was determined to induce serious eye damage on the cornea of the bovine eye.
- Executive summary:
A study was conducted to determine the eye irritation potential of test substance using the in vitro Bovine Corneal Opacity and Permeability (BCOP) test method according to OECD Guideline 437, in compliance with GLP. The BCOP test method can identify chemicals inducing serious eye damage and chemicals not requiring classification for eye irritation or serious eye damage. Fresh bovine eyes were obtained from the slaughterhouse on the day of the test. The cattle were between 12 and 60 months old. The corneas were screened for test requirements, prepared and mounted in corneal holders. Prior to treatment, the test system was previously incubated with cMEM without phenol red at 32 ± 1°C for 1 h and Corneal opacity was determined. The test substance preparation [20% suspension in Hank’s Balanced Salt Solution (HBSS)] was incubated on the cornea for 4 h at 32 ± 1°C. After removal of the test substance, opacity and permeability values were measured. For each treatment group [negative control solution (HBSS), test substance and positive control (20% imidazole solution)], three replicates were used. In the negative control, no signs of eye irritation were observed. The positive control induced serious eye damage, which would be classified as GHS category I .The negative control and the positive control met the validity criteria. The calculated IVIS (In Vitro Irritancy Score) was 121.95. Under study conditions, the test substance was therefore determined to induce serious eye damage on the cornea of the bovine eye (Geitlinger, 2018).
Reference
Opacity and Permeability Values
The illuminance (unit: LUX) values measured before and after exposure
Parameter |
Negative Control |
Test substance |
Positive Control |
||||||
1. Rep. |
2. Rep. |
3. Rep. |
1. Rep. |
2. Rep. |
3. Rep. |
1. Rep. |
2. Rep. |
3. Rep. |
|
(I) Measured values before exposure |
968 |
995 |
972 |
999 |
1022 |
975 |
994 |
989 |
979 |
(I) Measured values after exposure |
969 |
938 |
926 |
250 |
243 |
267 |
358 |
390 |
352 |
Rep. = Replicate
Opacity Values Negative Control
Parameter |
Negative Control |
||
1. Rep. |
2. Rep. |
3. Rep. |
|
Opacity before exposure |
3.85 |
2.67 |
3.67 |
Opacity after exposure |
3.80 |
5.23 |
5.81 |
Opacity Difference |
-0.04 |
2.56 |
2.14 |
Mean Opacity Difference |
1.55 |
Opacity Values Test substance and Positive Control
Parameter |
Test substance |
Positive Control |
||||
1. Rep. |
2. Rep. |
3. Rep. |
1. Rep. |
2. Rep. |
3. Rep. |
|
Opacity before exposure |
2.51 |
1.56 |
3.54 |
2.72 |
2.93 |
3.36 |
Opacity |
128.11 |
132.93 |
117.44 |
77.57 |
67.97 |
79.56 |
Opacity |
125.60 |
131.37 |
113.90 |
74.85 |
65.04 |
76.20 |
Opacity Difference corrected |
124.05 |
129.82 |
112.35 |
73.30 |
63.49 |
74.65 |
Mean Opacity Difference corrected |
122.08 |
70.48 |
For the permeability measurement, three replicates for each treatment group were measured three times. cMEM without phenol red was measured as blank value.
Optical density at 492 nm of Blank
Parameter |
cMEM without phenol red |
1. Measurement |
0.041 |
2. Measurement |
0.035 |
3. Measurement |
0.042 |
Mean |
0.039 |
Optical density at 492 nm of Negative Control, Test substance and Positive Control
Parameter |
Negative Control |
Test substance |
Positive Control |
||||||
1. Rep. |
2. Rep. |
3. Rep. |
1. Rep. |
2. Rep. |
3. Rep. |
1. Rep. |
2. Rep. |
3. Rep. |
|
1 Measurement |
0.068 |
0.050 |
0.060 |
0.040 |
0.050 |
0.060 |
1.435 |
2.137 |
1.411 |
2. Measurement |
0.064 |
0.047 |
0.054 |
0.036 |
0.048 |
0.057 |
1.463 |
2.140 |
1.413 |
3. Measurement |
0.069 |
0.048 |
0.050 |
0.039 |
0.049 |
0.057 |
1.465 |
2.143 |
1.396 |
|
|||||||||
1. Measurement – blank |
0.0287 |
0.0107 |
0.0207 |
0.0007 |
0.0107 |
0.0207 |
1.3957 |
2.0977 |
1.3717 |
2. Measurement – blank |
0.0247 |
0.0077 |
0.0147 |
-0.0033 |
0.0087 |
0.0177 |
1.4237 |
2.1007 |
1.3737 |
3. Measurement – blank |
0.0297 |
0.0087 |
0.0107 |
-0.0003 |
0.0097 |
0.0177 |
1.4257 |
2.1037 |
1.3567 |
Mean of each replicate |
0.0277 |
0.0090 |
0.0153 |
-0.0010 |
0.0097 |
0.0187 |
1.4150 |
2.1007 |
1.3673 |
Mean of the 3 replicates |
0.0173 |
-- |
-- |
||||||
Corrected |
-- |
-- |
-- |
-0.0183 |
-0.0077 |
0.0013 |
1.3977 |
2.0833 |
1.3500 |
Corrected mean of the 3 replicates |
-- |
-0.0082 |
1.6103 |
IVIS Value
The calculated IVIS for each replicate and the corresponding means
Test Group |
IVIS |
Mean IVIS |
Relative Standard Deviation IVIS |
Negative Control |
0.37 |
1.81 |
69.47% |
2.69 |
|||
2.37 |
|||
Test substance |
123.78 |
121.95 |
7.22% |
129.71 |
|||
112.37 |
|||
Positive Control |
94.27 |
94.64 |
0.35% |
94.74 |
|||
94.90 |
Validityof the Study: The validity criteria and findings
Parameter |
Criterion |
Found |
Assessment |
IVIS of negative control HBSS |
≤3 |
1.81 |
ok |
IVIS of positive control |
70.92 – 157.64 |
94.64 |
ok |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irreversible damage)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Skin irritation
A study was conducted to determine skin corrosion potential of the test substance using the reconstructed human epidermis (RHE) test method according to OECD Guideline 431, in compliance with GLP. Two tissues of the human skin model EpiDermTM were treated with the test substance for 3 min and 1 h, respectively. Demineralised water was used as negative control and potassium hydroxide (8M) was used as positive control. After treatment, the respective substance was rinsed from the tissues. Then, cell viability of the tissues was evaluated by MTT, which can be reduced to a blue formazan. Formazan production was evaluated by measuring the optical density (OD) of the resulting solution. After treatment with the test substance, the mean value of relative tissue viability was reduced to 72.5% (3 min exposure) and 10.7% (1 h exposure), which qualifies as corrosive. Under the study conditions, the test substance was therefore considered as corrosive to skin (Andres, 2018).
Eye irritation
A study was conducted to determine the eye irritation potential of test substance using the in vitro Bovine Corneal Opacity and Permeability (BCOP) test method according to OECD Guideline 437, in compliance with GLP. The BCOP test method can identify chemicals inducing serious eye damage and chemicals not requiring classification for eye irritation or serious eye damage. Fresh bovine eyes were obtained from the slaughterhouse on the day of the test. The cattle were between 12 and 60 months old. The corneas were screened for test requirements, prepared and mounted in corneal holders. Prior to treatment, the test system was previously incubated with cMEM without phenol red at 32 ± 1°C for 1 h and corneal opacity was determined. The test substance preparation [20% suspension in Hank’s Balanced Salt Solution (HBSS)] was incubated on the cornea for 4 h at 32 ± 1°C. After removal of the test substance, opacity and permeability values were measured. For each treatment group [negative control solution (HBSS), test substance and positive control (20% imidazole solution)], three replicates were used. In the negative control, no signs of eye irritation were observed. The positive control induced serious eye damage, which would be classified as GHS category I .The negative control and the positive control met the validity criteria. The calculated IVIS (In Vitro Irritancy Score) was 121.95. Under study conditions, the test substance was therefore determined to induce serious eye damage on the cornea of the bovine eye (Geitlinger, 2018).
Justification for classification or non-classification
Skin irritation
In an in vitro skin irritation study (RHE), treatment with the test substance resulted in the mean value of relative tissue viability of 72.5% (3 min exposure) and 10.7% (1 h exposure). The test substance therefore warrants classification as Skin Corr. 1B - H314: Causes severe skin burns and eye damage according to EU CLP (EC 1272/2008) criteria.
Eye irritation
The calculated IVIS (In Vitro Irritancy Score) in an in vitro eye irritation study (BCOP) was 121.95. The test substance therefore warrants classification as Eye Damage 1 - H318: Causes serious eye damage according to EU CLP (EC 1272/2008) criteria.
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.