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EC number: - | 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
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:
- 15 February 2018 - 12 March 2018
- Reliability:
- 1 (reliable without restriction)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 431 (In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method)
- Deviations:
- yes
- Remarks:
- Deviations were considered to have not affected the integrity or validity of the study.
- GLP compliance:
- yes
- Test system:
- isolated skin discs
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Cell source:
- foreskin from multiple donors
- Source strain:
- other:
- Justification for test system used:
- System used to supplant in-vivo testing
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- Test System
EpiDerm™ Reconstructed Human Epidermis Model Kit
Supplier: MatTek
Date received: 22 February 2018
EpiDermTM Tissues (0.63cm2) lot number :25882
Assay Medium lot number:021518TMA
Upon receipt of the EpidermTM tissues, the sealed 24-well plate was stored in a refrigerator until use. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- 50 uL
- Duration of treatment / exposure:
- 3 min/60 min
- Duration of post-treatment incubation (if applicable):
- NA
- Number of replicates:
- 2 ea. for postive and negative controls and substance at 3min, 60 min.
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 1/ @3 minutes
- Value:
- ca. 97.8
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 2/@ 60 min
- Value:
- ca. 111.8
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Interpretation of results:
- study cannot be used for classification
- Conclusions:
- Predicted to be non-corrosive to the skin via employed test system. See attached background material.
- Executive summary:
Introduction
The purpose of this test is to evaluate the corrosivity potential of the test item using the EpiDerm™ Human Skin Model after treatment periods of 3 and 60 minutes.
Corrosion is directly related to cytotoxicity in the EpiDerm™ tissue. Cytotoxicity is determined by the reduction of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) to formazan by viable cells in the test item treated tissues relative to the corresponding negative control. The results are used to make a prediction of the corrosivity potential of the test item.
Methods
Duplicate tissues were treated with the test item for exposure periods of 3 and 60 minutes. Negative and positive control groups were treated for each exposure period. The test item was found to have the potential to cause color interference and therefore additional tissues were incorporated for color correction purposes. The test item was also found to directly reduce MTT and therefore, an additional procedure using freeze-killed tissues was performed. A third set of controls was included; comprising freeze-killed tissues, in order to prevent a double correction from a colored test item that also reduces MTT. At the end of the exposure period the test item was rinsed from each tissue before each tissue was taken for MTT-loading. After MTT loading each tissue was placed in 2 mL Isopropanol for MTT extraction.
At the end of the formazan extraction period each well was mixed thoroughly and triplicate 200 μL samples were transferred to the appropriate wells of a pre-labeled 96-well plate. The optical density (OD) was measured at 570 nm (OD570).
Data are presented in the form of percentage viability (MTT reduction in the test item treated tissues relative to negative control tissues). See attached background material.
- Endpoint:
- skin irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 28 March 2018 - 03 April 2018
- 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)
- Deviations:
- no
- GLP compliance:
- yes
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Justification for test system used:
- Full validation study of EpiSkinTM recontructed human epidermis model showed evidence of being a reliable and relevant stand-alone test for predicting rabbit skin irritaion when the end point is measured by MTT reduction and for being used as a replacement for the Draize Skin Irritation Test for the purpose of distinguishing between Irritating and Non-irritating test items.
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EPISkin(TM) Reconstituted Human Epidermis Model Kit
- Tissue batch number(s): 18-EKIN-013
- Delivery date: 27 March 2018
- Date of initiation of testing: 28 March 2018
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 37 °C
- Temperature of post-treatment incubation (if applicable): 37 °C
REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: Rinsed using a wash bottle containing PBS with Ca++ and Mg++
- Observable damage in the tissue due to washing: None reported
- Modifications to validated SOP: No
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 0.3 mg/mL
- Incubation time: 3 hours
- Spectrophotometer: Labtech LT-4500 microplate reader
- Wavelength: 570 nm
- Filter: No
NUMBER OF REPLICATE TISSUES: 3
CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE
- Water killed tissues
- Method of calculation used: No interference due to direct reduction of MTT occurred. The results were therefore not included for quantitative correction.
NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 1
PREDICTION MODEL / DECISION CRITERIA
- The test substance is considered to be corrosive to skin if the viability after 15 minutes exposure followed by 42 hour post exposure observation is less than 50%
- The test substance is considered to be non-corrosive to skin if the viability after 15 minutes exposure followed by 42 hour post exposure observation is greater than 50% - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- 10 µL of test item added to 2 mL of a 0.3 mg/mL MTT solution
- Duration of treatment / exposure:
- 15-minute exposure period.
- Duration of post-treatment incubation (if applicable):
- 42-hour post-exposure incubation period.
- Number of replicates:
- Performed in triplicate
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- Test material
- Value:
- 84.7
- 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: No
- Direct-MTT reduction: test item directly reduced MTT.
- Colour interference with MTT: test item was found to produce a coloured solution which may interfere with the MTT endpoint. Additional colour correction tissues were incorporated, however the results obtained indicated no colour interference occurred.
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: Yes
- Acceptance criteria met for positive control: Yes
- Acceptance criteria met for variability between replicate measurements: Yes - Interpretation of results:
- GHS criteria not met
- Conclusions:
- The test item was classified as non-irritant.
- Executive summary:
The purpose of this test was to evaluate the skin irritation potential of the test item using the EPISKINTM reconstructed human epidermis model to measure cytotoxicity following topical exposure to the test item by means of colorimetric MTT reduction assay relative to the negative control (Dulbecco's Phosphate Buffered Saline (DPBS) with Ca++ and Mg++).
Triplicate tissues were treated with the test item for an exposure period of 15 minutes. At the end of the exposure period each tissue was rinsed before incubating for 42 hours.The test item was found to have potential to cause color interference and therefore additional tissues were incorportated for color correction purposes. An assessment of the test item's capability to directly reduce MTT was found to directly reduce MTT and therefore additional non-viable tissues were incorporated intro the testing for correction purposes. A third set of controls was included, compromising freeze-killed tissues, in order to prevent a double correction from a colored test item that also reduces MTT. At the end of the post-exposure incubation period each tissue was taken for MTT-loading. The maintenance medium from possible inflammatory mediator determination. After MTT-loading a total biopsy of each epidermis was placed into micro tubes containing acidified isopropanol for extraction of formazan crystals out of the MTT-loaded tissues.
At the end of the formazan extraction period each tube was mixed thoroughly and duplicate 200 µL samples were transferred to the appropriate wells of a pre-labeled 96 -well plate. The optical density was measured at 570 nm.
The relative mean percentage viability of the test item treated tissues was 84.7% after the 15 minute exposure period and 42-hours post-exposure incubation period.
The test item was classified as non-irritant.
Referenceopen allclose all
Table 1: Results
Test solution |
OD570 of tissues |
Mean OD570 of tissues |
± SD of OD570 |
Relative individual viability (%) |
Relative mean viability (%) |
± SD of Relative mean viability (%) |
Negative control |
0.522 |
0.601 |
0.070 |
86.9 |
100 |
11.6 |
0.625 |
104.0 |
|||||
0.655 |
109.0 |
|||||
Positive control |
0.039 |
0.031 |
0.009 |
6.5 |
5.2 |
1.6 |
0.021 |
3.5 |
|||||
0.034 |
5.7 |
|||||
Test Material |
0.506 |
0.509 |
0.080 |
84.2 |
84.7 |
13.3 |
0.591 |
98.3 |
|||||
0.431 |
71.7 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not 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:
- 16 February 2018 - 19 April 2018
- Reliability:
- 1 (reliable without restriction)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
- Deviations:
- no
- GLP compliance:
- yes
- Irritation parameter:
- in vitro irritation score
- Run / experiment:
- 1
- Value:
- ca. 6
- Vehicle controls validity:
- not specified
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of irritation
- Irritant / corrosive response data:
The In Vitro irritancy scores are summarized as follows:
Treatment In Vitro Irritancy Score
Test Item 6.0
Negative Control 0.4
Positive Control 43.2- Interpretation of results:
- study cannot be used for classification
- Conclusions:
- The IVIS of 6.0 was determined for the test item.
- Executive summary:
The corneas treated with the test item were clear post treatment and post incubation. The corneas treated with the negative control item were clear post treatment and post incubation. The corneas treated with the positive control item were cloudy post treatment and post incubation.
- Endpoint:
- eye irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 13 APR 2018 - 26 NOV 2018
- 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)
- Deviations:
- yes
- Remarks:
- deviations were considered to have not affected the integrity or validity of the study.
- GLP compliance:
- yes
- Irritation parameter:
- other: Percent viability
- Value:
- ca. 46.599
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- positive indication of irritation
- Irritant / corrosive response data:
- The mean relative absorption value of the tissues corresponding to the cornea viability decreased to 46.6% compared to the value of the negative control (classification cut-off: . 60%). The viability resulted from the test item exposed tissues was originally higher than the cut-off value of 60% (68.46 %). The test item was able to reduce MTT by 21.01 percentage points compared to the freeze killed negative control. This value was subtracted from the viability value resulted from the test item exposed tissues in order to correct the MTT interference and therefore the classification changed since 46.599 % is below the classification cut off.
- Interpretation of results:
- study cannot be used for classification
- Conclusions:
- Under the experimental conditions reported, test item possesses an eye irritating potential.
- Executive summary:
This in vitro study was performed to assess the eye irritation potential by means of the Human Cornea Model Test.
Additional tests with viable and freeze-killed tissues were performed, since the test item showed a milky color in the color interference pre-test and proved to be a MTT reducer.
Tissues of the human cornea model EpiOcular™ were treated with the test item, the positive and the negative control for 30 minutes each in duplicate.
50 μL of the test item and of the controls, respectively, were applied to each tissue, spread to match the tissue size.
Treatment with the positive control induced a decrease in the mean relative absorbance compared with the negative control to 42.83%, thus the validity of the test system is ensured.
Irritating effects were observed following 30 minutes incubation. The mean relative absorption value of the tissues corresponding to the cornea viability decreased to 46.6% compared to the value of the negative control (classification cut-off: ≤ 60%). The viability resulted from the test item exposed tissues was originally higher than the cut-off value of 60% (68.46 %). The test item was able to reduce MTT by 21.01 percentage points compared to the freeze killed negative control. This value was subtracted from the viability value resulted from the test item exposed tissues in order to correct the MTT interference and therefore the classification changed since 46.599 % is below the classification cut off.
Referenceopen allclose all
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
In accordance with regulation EC 1272/2008, the test material is classified as H319 Causes serious eye irritation (Category 2). THe substance is not classified for skin irritation or corrosion.
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