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EC number: 220-189-5 | CAS number: 2657-00-3
- 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 in vitro: not irritant
OECD 439: negative
Skin irritation in vivo: insufficient for classification according to CLP (UN/GHS)
Eye irritation in vitro: irritant Cat 2
OECD 437: inconclusive, not cat 1
OECD 492: cat 1 or 2
Eye irritation in vivo: insufficient for classification according to CLP (UN/GHS)
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:
- June 28, 2017 - August 22, 2017
- 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)
- Version / remarks:
- Commission Regulation (EU) No. 640/2012 amending, for the purpose of its adaption to technical progress, Regulations (EC) No. 440/2008 laying down test methods pursuant to Regulation (EC) No. 1907/2006 of the European Parliament and the council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH).
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
- Version / remarks:
- July 28, 2015
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Skinethic skin irritation test -42bis Standard operating procedure (SOP) 2009
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Specific details on test material used for the study:
- TREATMENT OF TEST MATERIAL PRIOR TO TESTING
No pre-treatment; the test item was applied neat to the tissues. - 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: EpiSkin/SkinEthic Laboratories, Lyon, France)
- Source: human keratinocytes cultured on a polycarbonate filter in conditions which permit their terminal differentiation
- Format: 24 well plate
- Batch: 17-RHE-083
- Expires: August 7, 2017
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.
DYE BINDING METHOD
- Dye used in the dye-binding assay: MTT
- Spectrophotometer:ELx800, BioTek Instruments GmbH, Bad Friedrichshall, Germany at 570 nm
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 1 mg/mL
- Incubation time: 3 hours
- Spectrophotometer: ELx800, BioTek Instruments GmbH, Bad Friedrichshall, Germany
- Wavelength: 570 nm
- Linear OD range of spectrophotometer: 0 - 3.0
FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
Acceptance Criteria Result
Cell viability (570 nm optical density, MTT test) OD >0.7 OD 1.2 (CV = 5.5 %)
Barrier function integrity test
(Exposure time inducing 50%
viability using Triton X-100 1%) 4.0h ≤ ET50 ≤ 10.0h 4.4h
Histological observation
(HES stained vertical paraffin sections) Number of cell layers ≥ 4 5.5 cell layers
Absence of significant
histological abnormalities. Absence of significant histological abnormalities.
Well differentiated epidermis Satisfactory
consisting of basal, spinous,
granular layers and a stratum c
orneum.
NUMBER OF REPLICATE TISSUES: 3
NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 1 experiment
PREDICTION MODEL / DECISION CRITERIA:
A test item is considered as non-irritant to skin (UN GHS No Category) if the tissue viability after exposure and post-treatment incubation is > 50%.
A test item is identified as requiring classification and labelling according to UN GHS (Category 2 or Category 1) if the mean percent tissue viability after exposure and post-treatment incubation is ≤ 50%. Since the in vitro skin irritation test according to OECD 439 cannot resolve between UN GHS Categories 1 and 2, further information on skin corrosion is required to decide on its final classification. - 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:
- 88.8
- 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:
- no 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:
Acceptance Criterion Result
Negative control OD ≥ 0.8 and ≤ 3.0 2.065 to 2.242
Acceptability of the Positive and Negative Control stated by Episkin/SkinEthic Laboratories:
Acceptance Criterion Result
Mean OD negative control ≥ 1.2 2.140
Mean viability positive control < 40% 1.3%
SD of group-mean value ≤ 18% 7.7% (positive control)
4.3% (negative control)
Acceptability of the Positive and Negative Control based on Historical Data of the Testing Laboratory:
Acceptance Criterion Result
Mean OD negative control ≥ 1.455 2.140
Mean viability positive control ≤ 2.97% 1.3%
Test Item Data Acceptance Criteria:
Acceptance Criterion Result
SD of group-mean value ≤ 18% 3.4%
The study met all acceptance criteria. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- This study was performed according to GLP and the methods applied are fully compliant with OECD TG 439. Under the conditions of the present study, the test item is not considered to possess an irritant potential to skin (UN GHS: No Category).
- Executive summary:
This study was performed according to GLP and the methods applied are fully compliant with OECD TG 439. Under the conditions of the present study, the test item is not considered to possess an irritant potential to skin (UN GHS: No Category).
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1981-08-11 to 1981-08-14
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Remarks:
- Only a brief summary of the study is available
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- not applicable
- GLP compliance:
- not specified
- Specific details on test material used for the study:
- Appearance: yellow crystals
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
Before application, the test material was moistened with 0.4 mL 0.9% NaCl solution - Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
-Source: Hoechst AG, Frankfurt, Germany
-Weight at study initiation: 1.9- 2.7 kg
-Housing: single
-Diet: ad libitum
-Water: ad libitum - Type of coverage:
- occlusive
- Preparation of test site:
- other: clipped and scarified
- Vehicle:
- physiological saline
- Controls:
- not required
- Amount / concentration applied:
- 0.5 g per animal
- Duration of treatment / exposure:
- 24 hours
- Observation period:
- up to 8 days
- Number of animals:
- 6
- Details on study design:
- TEST SITE
-Area of exposure: 6*3 cm on the flank
-Type of wrap if used: adhesive plaster (Hansamed) and polyethylene foil
REMOVAL OF TEST SUBSTANCE
-Method: not specified
-Time after start of exposure: 24 hours
OBSERVATION TIME POINTS
-After removal of the plaster and after 48 and 72 hours
d then daily up to experimental day 8
SCORING SYSTEM
-According to OECD GL 404 - Irritation parameter:
- overall irritation score
- Basis:
- mean
- Time point:
- other: not further specified
- Score:
- 1.6
- Reversibility:
- not specified
- Remarks on result:
- probability of mild irritation
- Irritant / corrosive response data:
- In two rabbits effects on the skin (dry, rough, cracked, eschar formation) was noted
- Interpretation of results:
- study cannot be used for classification
Referenceopen allclose all
Group | Time / [min] | Mean OD | Mean Relative viability / [%] |
Negative Control | 42 | 2.140 | 100 |
Positive Control | 42 | 0.028 |
1.3 |
Test Material |
42 |
1.846 |
88.8 |
Study design
In this study performed equivalent to OECD GL 404, 500 mg of the test item was mixed with physiological saline soution to ensure good contact to the skin. Afterwards, the test material was applied to clipped and scarified skin for a 24 hours period under occlusive conditions. Scoring was performed after pathch removal (24 h), and after 48, and 72 hours.
Results
Under the conditions of the present study, the treatment caused a mild irritation (mean score: 1.6).
Conclusion
A mild irritating potential could be detected.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1981
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Remarks:
- Only a brief summary of the study is available
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Deviations:
- not applicable
- GLP compliance:
- not specified
- Specific details on test material used for the study:
- Description: yellow crystals
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
-Source: Hoechst AG, Frankfurt, Germany
-Weight at study initiation: 1.9 - 2.7 kg
-Housing: groupwise
-Diet: ad libitum
-Water: ad libitum - Vehicle:
- physiological saline
- Controls:
- no
- Amount / concentration applied:
- 100 mg test item moistened with 0.04 mL physiological saline solution
- Duration of treatment / exposure:
- 24 hours
- Observation period (in vivo):
- up to 72 hrs
- Number of animals or in vitro replicates:
- 6
- Details on study design:
- A volume of 100 mg of the test material was instilled into the conjunctival sac of the left eye, while the right eye remained untreated and was used for control purposes.
REMOVAL OF TEST SUBSTANCE
-The eyes were rinsed 24 hrs after application.
SCORING SYSTEM: according to OECD GL 405
The 48/72 hrs score was obtained after installation of one drop of a 0.01% fluorescein sodium. - Irritation parameter:
- overall irritation score
- Basis:
- mean
- Time point:
- other: 7 hours
- Score:
- 6
- Reversibility:
- not specified
- Remarks on result:
- no indication of irritation
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The test material gave no indication for an eye irritation potential in rabbits.
- Executive summary:
This study was performed equivalent to OECD GL 405 and gave no indication for an eye irritation potential in rabbits.
- Endpoint:
- eye irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- June 28, 2017 - August 14, 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:
- 2013
- 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:
- Commission Regulation (EU) 2017/735 of 14 February 2017 amending, for the purpose of its adaption to technical progress, the Annex to Regulation (EC) No 440/2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH).
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Specific details on test material used for the study:
- PREPARATION OF THE TEST MATERIAL
The test item was prepared as a 20% (w/v) solution 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. - 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: 16435011
Storage: 2 to 8°C
Released until: September 2019
POSITIVE CONTROL: 750 µL
Designation: Art. 814223
Synonym: Imidazole
Supplier: Merck KGaA, Germany
Batch: S6746923
Purity (GC) 99.8% (a/a)
Storage: At room temperature
Released until: August 31, 2018
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:
- 3.4
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- not determinable
- Remarks:
- According to OECD 437 no prediction can be made regarding the eye hazard potential of the test item.
- Other effects / acceptance of results:
- OTHER EFFECTS:
- All corneas treated with the test item preparation showed a slight yellowish stain after removing the test item preparation by washing with wash medium.
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: After treatment with the negative control (0.9% sodium chloride solution) the calculated IVIS was 0.2 and, thus, within three standard deviations of the current historical mean of the negative control (IVIS: -1.4 – 3.2).
- Acceptance criteria met for positive control: After treatment with the positive control (20% Imidazole) the calculated IVIS was 106.4 and, thus, also within two standard deviations of the current historical mean of the positive control (IVIS 80.5 – 133.0).
Therefore, the study fulfilled the acceptance criteria. - Interpretation of results:
- other: Under the conditions of the present study, the eye hazard potential of the test item cannot be predicted.
- Conclusions:
- Under the conditions of the present study, the eye hazard potential of the test item cannot be predicted.
- 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, the eye hazard potential of the test item cannot be predicted.
- Endpoint:
- eye irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- August 17, 2017 - November 8, 2017
- 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:
- October 9, 2017
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: DB-ALM Protocol No. 164: Ocular Irritation Assay for Chemicals using EpiOcular™ EIT,
- Version / remarks:
- September 14, 2015
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: EpiOcular Eye Irritation Test (OCL-200-EIT) for the prediction of acute ocular irritation of chemicals; For use with MatTek Corporation`s Reconstructed Human EpiOcular Model; MatTek Corporation
- Version / remarks:
- June 29, 2015
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Specific details on test material used for the study:
- TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: No pre-treatment, the test item was applied neat to the tissues. - Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent positive control
- yes, concurrent negative control
- Amount / concentration applied:
- TEST MATERIAL: 50 mg per tissue
NEGATIVE / VEHICLE CONTROL: 50 µL per tissue
Sterile deionized water was used as negative control.
POSITIVE CONTROL: 50 µL per tissue
Designation: Methyl acetate
Supplier: MatTek In Vitro Life Science Laboratories
Lot-No.: 032817ISA
Catalog #: TC-MA
Purity (GC): 99.7%
Appearance: Colorless liquid
Expiration date: March 28, 2018
Storage: 15 to 30°C - Duration of treatment / exposure:
- 6 hours
- Number of animals or in vitro replicates:
- in vitro: duplicate design
- Irritation parameter:
- other: Viability %
- Run / experiment:
- Run 1 / Experiment 1
- Value:
- 4.4
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- positive indication of irritation
- Remarks:
- According to OECD 492 the test item is labeled irritant (UN GHS Category 1 or Category 2).
- Other effects / acceptance of results:
- OTHER EFFECTS:
- Visible damage on test system: No observations
ACCEPTANCE OF RESULTS:
1. The negative control OD is >0.8 and <2.5 (1.184 and 1.186).
2. The mean relative viability of the positive control is below 50% of the negative control viability (17.3%).
3. The difference of viability between the two relating tissues of a single chemical is <20% (values between 0.1% to 1.5%) in the same run (for positive and negative control tissues and tissues of single chemicals).
The study met all acceptance criteria - Interpretation of results:
- other: The test item is labeled irritant (UN GHS Category 1 or Category 2).
- Conclusions:
- Under the conditions of the present study, the test item did show an eye hazard potential. The test item is labeled irritant (UN GHS Category 1 or Category 2).
- Executive summary:
This study was performed according to GLP and the methods applied are fully compliant with OECD TG 492. Under the conditions of the present study, the test item did show an eye hazard potential. The test item is labeled irritant (UN GHS Category 1 or Category 2).
Referenceopen allclose all
Opacity |
Permeability |
IVIS |
||||
per cornea |
per group (mean value) |
SD |
||||
Negative control |
0.9% NaCl Solution |
0.0 | 0.002 |
0.030 |
0.2 |
0.4 |
0.0 |
0.003 |
0.045 |
||||
0.6 |
0.004 |
0.660 |
||||
Positive control |
20% Imidazole solution |
71.0 |
2.506 |
108.590 |
106.4 |
2.3 |
71.2 |
2.352 |
106.480 |
||||
72.4 |
2.112 |
104.080 |
||||
Test item |
Test item |
4.7 |
0.017 |
4.955 |
3.4 |
1.5 |
2.8 |
0.015 |
3.025 |
||||
1.8 |
0.018 |
2.070 |
Mean OD | Mean Viability | |
Negative Control | 1.185 | 100.0% |
Positive Control | 0.204 | 17.3% |
Test Item | 0.052 | 4.4% |
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 provided information there is no need for classification for skin irritation according to the EU Regulation (EC) No 1272/2008 on Classification, Labelling and Packaging of Substances and Mixtures, as amended for the 10th time in Regulation (EU) No 2017/776.
Based on the OECD 437 result eye damage cat 1 can be excluded. Taking all test results into account there is need for classification for eye irritation category 2 according to the EU Regulation (EC) No 1272/2008 on Classification, Labelling and Packaging of Substances and Mixtures, as amended for the 10th time in Regulation (EU) No 2017/776. Based on Test
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