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EC number: 224-166-0 | CAS number: 4221-80-1
- 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
The test substance does not give an indication of an irritant property to skin and eye.
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:
- 30 Sep 2014 - 21 Oct 2014
- 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)
- Qualifier:
- according to guideline
- Guideline:
- other: Commission Regulation (EC) No 440/2008 of 30 May 2008 laying down test methods pursuant to Regulation (EC) No 1907/2006, Part B: Methods for the determination of toxicity and other health effects: In Vitro Skin Corrosion: Human Skin Model Test
- GLP compliance:
- yes (incl. QA statement)
- Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature - Test system:
- human skin model
- Cell type:
- non-transformed keratinocytes
- Details on animal used as source of test system:
- The EpiDermTM model consists of normal, human-derived epidermal keratinocytes which have been cultured to form a multi layered, highly differentiated model of the human epidermis. It 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. The EpiDermTM tissues (surface 0.6 cm²) are cultured on specially prepared cell culture inserts (MILLICELLs, 10 mm ∅) and commercially available as kits (EpiDerm™ 200), containing 24 tissues on shipping agarose.
Supplier: MatTek In Vitro Life Science Laboratories, Bratislava, Slovakia - Vehicle:
- unchanged (no vehicle)
- Details on test system:
- The EpiDermTM model consists of normal, human-derived epidermal keratinocytes which have been cultured to form a multi layered, highly differentiated model of the human epidermis. It 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. The EpiDermTM tissues (surface 0.6 cm²) are cultured on specially
prepared cell culture inserts (MILLICELLs, 10 mm ∅) and commercially available as kits (EpiDerm™ 200), containing 24 tissues on shipping agarose.
Supplier: MatTek In Vitro Life Science Laboratories, Bratislava, Slovakia - Control samples:
- other: Control tissues were concurrently treated with 50 μL of de-ionized water (negative control, NC) or with 50 μL of 8 N potassium hydroxide (positive control, PC).
- Amount/concentration applied:
- 25 μL de-ionized water was applied first. Thereafter, a bulk volume of 25 μL of the solid test material was applied with a sharp spoon and homogeneously distributed with the water.
- Duration of treatment / exposure:
- 3 minutes at room temperature or 1 hour in the incubator
- Number of replicates:
- Two tissues per exposure time.
- Details on study design:
- The tissues were washed with PBS to remove residual test material 3 minutes or 1 hour after start of the application treatment.
Rinsed tissues were kept in 24-well plates (holding plates) at room temperature on assay medium until all tissues per application time were dosed and rinsed. The assay medium was then replaced by MTT solution and tissues were incubated for 3 hours.
After incubation, the tissues were washed with PBS to stop the MTT-incubation. The formazan that was metabolically produced by the tissues was extracted by incubation of the tissues in isopropanol. The optical density at a wavelength of 570 nm (OD570) of the extracts was determined spectrophotometrically. Blank values were established of 6 microtiter wells filled with isopropanol for each microtiter plate. - Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 3 min exposure; tissue 1
- Value:
- 107.4
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 3 min exposure; tissue 2
- Value:
- 107.9
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 3 min exposure; tissue 3
- Value:
- 108
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 1 h exposure; tissue 1
- Value:
- 96.5
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 1 h exposure; tissue 2
- Value:
- 106.1
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 1 h exposure; tissue 3
- Value:
- 101
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- The test substance is not able to reduce MTT directly, as determined in a pretest.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The test article does not show a skin irritation potential in the EpiDerm™ in vitro skin irritation and corrosion test strategy under the test conditions chosen.
- Executive summary:
The potential of the test article to cause dermal corrosion/irritation was assessed by a single topical application of 25 μL bulk volume (about 16 mg) of the undiluted test substance to a reconstructed three dimensional human epidermis model (EpiDerm™). For the corrosion test two EpiDerm™ tissue samples were incubated with the test substance for 3 minutes and 1 hour, respectively. Tissue destruction was determined by measuring the metabolic activity of the tissue after exposure/post-incubation using a colorimetric test. The reduction of mitochondrial dehydrogenase activity, measured by reduced formazan production after incubation with a tetrazolium salt (MTT) was chosen as endpoint. The formazan production of the testsubstance treated epidermal tissues is compared to that of negative control tissues. The quotient of the values indicates the relative tissue viability. The EpiDerm™ skin corrosion/irritation test showed the following results: The test substance is not able to reduce MTT directly. Corrosion test: The mean viability of the test-substance treated tissues determined after an exposure period of 3 minutes was 108%,and it was 101% after an exposure period of 1 hour. Based on the observed results it was concluded, that the test article does not show a skin irritation potential in the EpiDerm™ in vitro skin irritation and corrosion test strategy under the test conditions chosen.
Reference
Individual and mean OD570 values, individual and mean viability values
Exposure: 3 min | Exposure: 1 hour | ||||||
Test substance |
tissue 1 | tissue 2 | mean | tissue 1 | tissue 2 | mean | |
NC | mean OD570 | 1.689 | 1.716 | 1.703 | 1.987 | 1.880 | 1.934 |
viability [% of NC] | 99.2 | 100.8 | 100 | 102.8 | 97.2 | 100 | |
test article | mean OD570 | 1.828 | 1.838 | 1.833 | 1.866 | 2.052 | 1.959 |
viability [% of NC] | 107.4 | 107.9 | 108 | 96.5 | 106.1 | 101 | |
PC | mean OD570 | 0.341 | 0.383 | 0.362 | 0.190 | 0.224 | 0.207 |
viability [% of NC] | 20.0 | 22.5 | 21 | 9.8 | 11.6 | 11 |
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:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Version / remarks:
- 2012
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: The Food and Drug Administration of the U.S.A. in The Federal Register (17 September, 1964 § 191.12),
- Deviations:
- no
- GLP compliance:
- no
- Species:
- rabbit
- Details on test animals or tissues and environmental conditions:
- no data
- Vehicle:
- unchanged (no vehicle)
- Controls:
- not required
- Amount / concentration applied:
- 40 mg of the test item were instilled into each eye.
- Duration of treatment / exposure:
- single treatment
- Observation period (in vivo):
- daily
- Number of animals or in vitro replicates:
- 6 animals
- Details on study design:
- SCORING SYSTEM: Ocular reactions were scored by the method described by J.H. Draize in "Appraisal of the safety of Chemicals in foods, Drugs and Cosmetics" p 51.
- Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Remarks:
- all animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Irritation parameter:
- iris score
- Basis:
- mean
- Remarks:
- all animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 3
- Reversibility:
- fully reversible within: 4 days
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0.66
- Max. score:
- 3
- Reversibility:
- fully reversible within: 48 h
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 3
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #4
- Time point:
- 24/48/72 h
- Score:
- 0.66
- Max. score:
- 3
- Reversibility:
- fully reversible within: 48 h
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #5
- Time point:
- 24/48/72 h
- Score:
- 0.66
- Max. score:
- 3
- Reversibility:
- fully reversible within: 48 h
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #6
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 3
- Irritant / corrosive response data:
- Temporary mild conjunctival reactions were observed in four animals only. In the remaining two animals there was no observable response to treatment. A maximum group mean reaction score of 1 was established on day 1.
- Interpretation of results:
- GHS criteria not met
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Skin irritation
The potential for corrosive activity and skin irritation of the test article was assessed in vitro. Using the currently available methods a single in vitro assay may not always be sufficient to cover the full range of skin irritating/corrosion potential. Therefore, two in vitro assays were part of this in vitro skin irritation and corrosion test strategy: The Skin Corrosion Test (SCT) and Skin Irritation Test (SIT). The potential of the test item to cause dermal corrosion/irritation was assessed by a single topical application of 25 µl bulk volume (about 16 mg) of the undiluted test substance to a reconstructed three-dimensional human epidermis model (EpiDerm™). For the corrosion test two EpiDerm™ tissue samples were incubated with the test substance for 3 minutes and 1 hour, respectively. The irritation test was performed with three EpiDerm™ tissue samples, which were incubated with the test substance for 1 hour followed by a 42-hours post-incubation period. Tissue destruction was determined by measuring the metabolic activity of the tissue after exposure/post-incubation using a colorimetric test. The reduction of mitochondrial dehydrogenase activity, measured by reduced formazan production after incubation with a tetrazolium salt (MTT) was chosen as endpoint. The formazan production of the test substance treated epidermal tissues is compared to that of negative control tissues. The quotient of the values indicates the relative tissue viability. The EpiDerm™ skin corrosion/irritation test showed the following results: The test substance is not able to reduce MTT directly. The mean viability of the test-substance treated tissues determined after an exposure period of 3 minutes was 108%, and it was 101% after an exposure period of 1 hour. The mean viability of the test-substance treated tissues determined after an exposure period of 1 hour with about 42 hours post-incubation was 101%. Based on the observed results and applying the evaluation criteria it was concluded, that the test article does not show a skin irritation potential in the EpiDerm™ in vitro skin irritation and corrosion test strategy under the test conditions chosen.
This finding was supported by the results of an old summary report investigating the dermal irritation potential. Here, twenty-four hours after application to the unabraded skin of rabbits, there was no discernible evidence of erythema or edema with any of the materials.
Eye irritation
Aim of the study was to determine the degree of eye irritation/corrosion
of 6 rabbits caused by the test substance in 7 days. To that end, 40 mg
of the test item were instilled into each eye. The eyes were examined at
24, 48, 72 hours, then 1 week after the application. One day after the
treatment the test item caused conjunctivae irritant effects in 4 of 6
animals. No other symptoms were observed. 1 week after the treatment,
all animals were free of symptoms, so the study was terminated. The
animals individual mean scores (considering readings at 24, 48, and 72
hours after the treatment) were as follows: Cornea: 0 (mean value from
all animals); Iris: 0 (mean value from all animals); Conjunctivae: 2,
0.66, 0, 0.66, 0.66, 0. In conclusion, the test item applied to the
rabbits' eye mucosa caused slight conjunctivae irritant effects, fully
reversible within 4 days.
Justification for classification or non-classification
Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008 (CLP). As a result the substance is not considered to be classified for skin irritation and for eye irritation under Regulation (EC) No 1272/2008, as amended for the eighth time in Regulation (EU) No 2016/218.
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