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EC number: 610-202-6 | CAS number: 446299-80-5
- 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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Endpoint summary
Administrative data
Description of key information
Skin irritation (in vitro): Key study. Test method according to OECD 439, GLP study. The mean percent viability of the treated tissues was 98.9%, versus 1.5% in the positive control (5% SDS). Therefore, the test item is not irritant to the skin.
Serious eye damage/eye irritation: Key study. Method according to OECD guideline 492, GLP study. Under the conditions of the test, test item does not require classification for eye irritation or serious eye damage. It corresponds to the UN GHS No Category.
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:
- From 02-08-2022 to 25-08-2022
- 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:
- yes
- Remarks:
- Standard deviation between tissue repplicates was higher tham 18% for negative control. Positive control is compliant which means that the experiment is able to classify a test item.
- GLP compliance:
- yes (incl. QA statement)
- Test system:
- human skin model
- Remarks:
- (SkinEthic RHE model)
- Source species:
- human
- Cell source:
- foreskin from multiple donors
- Justification for test system used:
- The SkinEthic RHE model has been validated for irritation testing and its use is recommended by the
relevant OECD guideline for irritation testing (OECD No. 439); therefore, it was considered to be
suitable for this study. - Vehicle:
- unchanged (no vehicle)
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: SkinEthic RHE
- Tissue batch number(s): 22-RHE-112
- Production date: N/A
- Shipping date: -
- Delivery date: 23.08.2022
- Date of initiation of testing: 23.08.2022
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 41 minutes at room temperature.
- Temperature of post-treatment incubation (if applicable): 37ºC
REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: 25 x 1 mL of DPBS
- Observable damage in the tissue due to washing: no
- Modifications to validated SOP: no
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 300 μL of a MTT solution at 1.0 mg/mL
- Incubation time: 3 hours at 37ºC, 5% CO2
- Spectrophotometer: ELx800 absorbance microplate reader (BioTek)
- Wavelength: 570 nm
FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
- Viability: O.D. = 1.4 (Acceptance criterion: 1.0-3.0). Historical negative control mean OD range= 0.402-1.402 (OD measured after 1:2 dilution in isopropanol; acceptability criteria should be in the range ≥ 0.4 and ≤1.4)
- Barrier function: 5.4 h (Acceptance criterion: 4.77h < ET50< 8.72h)
- Morphology: Tissue viability and barrier function test are within the acceptable ranges and indicate appropriate formation of the epidermal barrier, the presence of a functinal stratum corneum, a viable basal cell layer and intermediate spinous and granular layers.
- Contamination: No.
NUMBER OF REPLICATE TISSUES: 3
CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE: there is no direct interaction between the test item and MTT.
NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 1
PREDICTION MODEL / DECISION CRITERIA
- The test item is considered as non-irritant to skin if the mean percent viability after 42 minutes exposure and 42 hours of post-treatment incubation is > 50%.
- The test item is identified as requiring classification and labelling according to UN GHS (Category 2) if the mean percent tissue viability after 42 minutes exposure and 42 hours of post-treatment incubation is ≤ 50% and the result of a skin corrosion test is “non corrosive”.
- The 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 42 minutes exposure and 42 hours of posttreatment incubation is ≤ 50% and in absence of information on a skin corrosion test. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 16 mg
NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 16 μL
POSITIVE CONTROL
- Amount(s) applied (volume or weight): 16 μL
- Concentration (if solution): 5% SDS - Duration of treatment / exposure:
- 41 minutes at room temperature
- Duration of post-treatment incubation (if applicable):
- 41 hours and 01 minutes at 37ºC, 5% CO2
- Number of replicates:
- 3
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- mean
- Value:
- 98.9
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Remarks:
- (distilled water)
- Positive controls validity:
- valid
- Remarks:
- 3.6% viability (5% SDS)
- Other effects / acceptance of results:
- - OTHER EFFECTS:
- Visible damage on test system: no
DEMONSTRATION OF TECHNICAL PROFICIENCY: yes. A full demonstration of proficiency was performed for the EpiSkin model, plus a reduced validation with the EpiDerm model, having into account that both models are very similar. Adequate results were obtained for the evaluated chemicals.
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes, mean OD = 0.900 (OD measured after 1:2 dilution in isopropanol; acceptability criteria should be in the range ≥ 0.4 and ≤1.4).
- Acceptance criteria met for positive control: yes, mean viability = 0.014% (acceptability criteria should be < 20%).
- Acceptance criteria met for variability between replicate measurements: no. SD of negative, positive and test item replicates were 30.0, 0.1 and 5.4% respectively (acceptablility criteria, SD ≤ 18%). - Interpretation of results:
- other: Not classified (CLP Regulation EC no. 1272/2008)
- Conclusions:
- The test substance can be considered as not irritant to skin as the mean percent viability of the treated tissues was found 98.9% in the in vitro RhE test.
- Executive summary:
An in vitro skin irritation test was conducted for the test item in a reconstructed human epidermis model (SkinEthic RHE model) according to OECD guideline 439 (GLP study). Three epidermis units, previously moistened with 10 μL of distilled water, were treated with 16 mg test item for 41 minutes at room temperature. Exposure of the test item was terminated by rinsing with 25 x 1 mL of DPBS. The epidermis units were then incubated for a 41 hours and 01 minutes post-treatment incubation period in culture plate filled with 300 μL of fresh medium at 37ºC, 5% CO2. The viability of each disk was assessed by incubating the tissues with MTT, extracting the precipitated formazan crystals using isopropanol during 1 hour 55 minutes under gentle agitation in the dark, and measuring the concentration of formazan by determining the OD at 570 nm, just after dilution of the extracts 1:2 in isopropanol. Under the test conditions, the mean percent viability of the treated tissues was 98.9%, versus 1.5% in the positive control (5% Sodium Dodecyl Sulfate). Standard deviation between tissue repplicates was higher tham 18% for negative control. Positive control is compliant which means that the experiment is able to classify a test item.Therefore, the test item is considered as not irritant to the skin.
Reference
Table 1. Table of results
Well ID | OD | Mean OD / disc (#) | Mean OD / product | Viability % | Mean viability % | SD viability | Conclusion | |
Negative control | SPL 1 | 0.648 0.536 0.585 | 0.589 | 0.900 | 65.4 | 100.0 | 30.0 | No Category |
SPL 2 | 1.177 1.007 0.922 | 1.035 | 115.0 | |||||
SPL 3 | 1.067 1.103 1.060 | 1.076 | 119.6 | |||||
Positive control | SPL 4 | 0.012 0.013 0.014 | 0.013 | 0.014 | 1.4 | 1.5 | 0.1 | Category 2 "Irritant" |
SPL 5 | 0.015 0.015 0.013 | 0.014 | 1.6 | |||||
SPL 6 | 0.015 0.014 0.014 | 0.014 | 1.6 | |||||
Test item PH-22/0484 | SPL 16 | 0.801 0.811 0.890 | 0.834 | 0.890 | 92.7 | 98.9 | 5.4 | No Category |
SPL 17 | 0.866 0.933 0.965 | 0.921 | 102.3 | |||||
SPL 18 | 0.873 0.926 0.949 | 0.916 | 101.8 |
#mean of 3 values (triplicate of the same extract)
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:
- From 20-09-2022 to 21-10-2022
- 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:
- no
- GLP compliance:
- yes (incl. QA statement)
- Species:
- human
- Details on test animals or tissues and environmental conditions:
- - Justification of the test method (e.g. ICE, EIT, RhCE) and considerations regarding applicability: The EpiOcular™ model and the corresponding test method have been validated for irritation testing in an international va
lidation study and its use is recommended by the relevant OECD guideline (OECD No. 492), and the method is applicable to mixtures, solids, liquids, semi-solids and waxes. Therefore, it was considered to be suitable for this study.
- Description of the cell system used, incl. certificate of authenticity and the mycoplasma status of the cell live: The 0.60 cm² Reconstructed human Cornea-like Epithelium (EpiOcularTM OCL-212, supplied by MatTek Corporation, batch No. 34989) were received on 19 October 2022.The same day, the tissues in their well shipping container were equilibrated to room temperature for 40 minutes. Then the inserts (filter + epithelium) were gently removed from the agarose while avoiding leaving agarose on the polycarbonate filter. They were placed in 6 wells culture plate which had been previously filled with 1 mL of 37°C pre-warmed culture medium (MatTek Corporation, batch No. 101722ISA) and incubated for 22 hours and 01 minutes at standard culture conditions. - Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent positive control
- yes, concurrent negative control
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50 mg - Duration of treatment / exposure:
- 6 hours
- Duration of post- treatment incubation (in vitro):
- 17 hours and 45 minutes
- Number of animals or in vitro replicates:
- 2 tissues per test substance and for each control were used.
- Details on study design:
- - Details of the test procedure used: Two tissues (0.6 cm2) were pre-wetted with 20 μL DPBS buffer, incubated for 30 min, then dosed topically with 50 μL test item and exposed for 30 min at 37ºC, 5%
CO2, ≥ 95% RH. After exposure, the tissues were rinsed with DPBS, transferred to fresh assay medium, and incubated for 12 min. Then, they were transferred to fresh medium again and incubated for 125 min at 37ºC, 5% CO2. The MTT assay for cell viability evaluation was performed on the tissues, by incubating them for 3 hours with MTT solution between 36.4ºC and 36.7ºC, 5% CO2. The precipitated formazan crystals were then extracted using isopropanol and quantified spectrophotometrically.
- Doses of test chemical and control substances used: test item applied at the dose of 50 mg and controls (negative and positive) 50 μL.
- Duration and temperature of exposure, post-exposure immersion and post-exposure incubation periods (where applicable): exposure 6 hours (±0.25 h) in culture medium at 37±2ºC, 5±1% CO2, ≥95% RH; post-exposure immersion 25 min (±2 min) at RT in culture medium; post-exposure incubation 18 h (±0.25 h) in culture medium at 37±2ºC, 5±1% CO2, ≥95% RH
- Number of tissue replicates used per test chemical and controls: 2 tissues per test substance and for each control were used.
- For hCE cells: number of runs and of hCE models used within each run: 2 runs
- Description of the method used to quantify MTT formazan, if applicable: Optical density by microtiter plate photometer.
- Description of evaluation criteria used including the justification for the selection of the cut-off point for the prediction model: According to OECD 492, the percentage tissue viability cut-off value distinguishing classified from non-classified test chemicals is 60%. Therefore, the test item is identified as not requiring classification if the mean percent tissue viability after exposure and post-exposure incubation is > 60%. Otherwise, the test item is identified as potentially requiring classification and labelling.
- Demonstration of proficiency in performing the test method before routine use by testing of the proficiency chemicals: The validity of the RhCE EpiOcular™ test at laboratory facility was demonstra
ted in a proficiency study. For this purpose 15 proficiency chemicals (indicated by the OECD 492 guideline) were tested. All of the 15 proficiency chemicals were correctly categorized.
- Positive and negative control means and acceptance ranges based on historical data: The OD values of the two replicates with negative control are practically 0.4.
- Acceptable variability between tissue replicates for positive and negative controls: The difference of viability between the 2 tissue replicates treated with the positive and negative controls is higher than 20%.
The test has correctly classified the positive control (Category 2 and 1). The test is therefore able to classify a product. Moreover, the OD mean value of the test item is higher than the OD mean values of negative and positive controls. Therefore, it can be concluded on the classification of the test item.
- Acceptable variability between tissue replicates for the test chemical: yes, 7.8% below 20% (OECD Guideline 492). - Irritation parameter:
- other: Cell viability (5)
- Run / experiment:
- 2
- Value:
- 111.9
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- OTHER EFFECTS:
- Visible damage on test system: no.
DEMONSTRATION OF TECHNICAL PROFICIENCY: yes.
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: The mean OD 570 of the negative control tissues must be > 0.8 and < 2.8. The mean OD values for negative control was 0.398. As the extract was diluted at 50% just before the OD measurement, the acceptability criteria should be in the range > 0.4 and < 1.25 for the negative control. Difference for tissues treated with negative control was higher than 20%. The test has correctly classified the positive control (Category 2 and 1). The test is therefore able to classify a product. Moreover, the OD mean value of the test item is higher than the OD mean values of negative and positive controls. Therefore, it can be concluded on the classification of the test item
- Acceptance criteria met for positive control: The mean relative viability of the positive control (methyl acetate) should be below 50% The mean viability of positive control tissues was 30.9 %. Difference for tissues treated with positive control was higher than 20%. The test has correctly classified the positive control (Category 2 and 1). The test is therefore able to classify a product. Moreover, the OD mean value of the test item is higher than the OD mean values of negative and positive controls. Therefore, it can be concluded on the classification of the test item - Interpretation of results:
- other: Not classified (CLP Regulation EC no. 1272/2008)
- Conclusions:
- Under the experimental conditions adopted and in accordance with the Regulation EC No. 1272/2008, the test item T-A10 does not require classification for eye irritation or serious eye damage. It corresponds to the UN GHS No Category.
- Executive summary:
An in vitro EIT study according to OECD 492 was conducted under GLP conditions to assess the irritation potential of the test item.EpiOcular™ tissues were used as test system. Preliminary tests were performed to detect the ability of the test item to directly reduce MTT as well as its colouring potential.Two tissues were pre-wetted with 20 μL DPBS buffer, incubated for 30 min, then dosed topically with 50 μg test item and exposed for 6 hours in culture medium at 37±2ºC, 5±1% CO2, ≥95% RH. After exposure, the tissues were rinsed with DPBS, transferred to fresh assay medium, and incubated for 25 min. Then, they were transferred to fresh medium again and incubated for 18 h at 37ºC, 5% CO2, ≥ 95% RH. The MTT assay for cell viability evaluation was performed on the tissues, by incubating them for 2 hours and 45 minutes with MTT solution. The precipitated formazan crystals were then extracted using isopropanol and quantified spectrophotometrically. The mean corrected percent tissue viability of the RhCE replicates treated with the test item was 111.9 % (considered as 100 %), versus 24.9 % in the positive control (Methyl acetate).Under the experimental conditions adopted and in accordance with the Regulation EC No. 1272/2008, the test item does not require classification for eye irritation or serious eye damage. It corresponds to the UN GHS No Category.
Reference
Table 1. Second run
Well ID | OD | Mean OD / disc | Mean OD / product | Viability % | Mean viability % | SD viability | Viability difference between replicates % | Conclusion | |
Negative control | SPL1 | 0.315 0.301 0.341 | 0.319 | 0.398 | 80.2 | 100.0 | 28.1 | 39.7 | No Category |
SPL 2 | 0.456 0.489 0.485 | 0.477 | 119.8 | ||||||
Positive control | SPL 3 | 0.202 0.193 0.185 | 0.193 | 0.123 | 48.5 | 30.9 | 24.9 | 35.2 | UN GHS Category 2 or 1 |
SPL 4 | 0.049 0.055 0.056 | 0.053 | 13.3 | ||||||
Test item PH-22/0484 | SPL 5 | 0.432 0.433 0.425 | 0.430 | 0.446 | 108.0 | 111.9 | 5.5 | 7.8 | No Category |
SPL 6 | 0.471 0.453 0.460 | 0.461 | 115.8 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Justification for classification or non-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.
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