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EC number: 947-738-8 | CAS number: -
- Life Cycle description
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- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
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- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
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- Toxicity to microorganisms
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- Toxicological Summary
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- Acute Toxicity
- Irritation / corrosion
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Endpoint summary
Administrative data
Description of key information
Skin corrosion category 1A based on OECD 431 study, as precautionary principle (the OECD 435 study showed no skin corrosion) for substance at concentration above 67%.
Additional testing showed no skin corrosive effects up to the concentration of 67% of the registered substance.
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:
- July-October 2017
- 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:
- from 29 July 2016
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.40 (In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test (TER))
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: MatTek Corporation Protocol for: In Vitro EpiDermTM Skin Corrosion Test (EPI-200-SCT) For use with MatTek Corporation’s Reconstructed Human Epidermal Model EpiDerm; Version 07/11/2014
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Cell source:
- other: single donor neonatal-foreskin tissue or, alternatively, adult breast skin
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EpiDermTM (MatTek)
- Tissue batch number(s): 25835
- Production date:
- Shipping date:
- Delivery date:
- Date of initiation of testing: 7 August 2017
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 37 +/- 1°C
- Temperature of post-treatment incubation (if applicable): 37 +/- 1°C
REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: 20 times with PBS after 3 and 60 minute incubation with test item; twice with PBS after incubation with MTT
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: final concentration 1 mg/mL
- Incubation time: 3 hrs
- Spectrophotometer: plate spectrophotometer
- Wavelength: 570 nm
- Filter:
- Filter bandwidth:
- Linear OD range of spectrophotometer:
NUMBER OF REPLICATE TISSUES: 2
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 [complete, e.g. the viability after 3 minutes exposure is less than 50%, or if the viability after 3 minutes exposure is greater than or equal to 50 % and the viability after 1 hour exposure is less than 15%.]
- The test substance is considered to be non-corrosive to skin if [complete, e.g. the viability after 3 minutes exposure is greater than or equal to 50% and the viability after 1 hour exposure is greater than or equal to 15%.] - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50 uL
NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 50 uL
POSITIVE CONTROL
- Amount(s) applied (volume or weight): 50 uL - Duration of treatment / exposure:
- 3-minute experiment
60-minute experiment - Duration of post-treatment incubation (if applicable):
- 3 hrs
- Number of replicates:
- 2
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- mean of 2 values
- Value:
- 17.6
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: after 3 minutes
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- mean of 2 values
- Value:
- 25.8
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: after 60 minutes
- Other effects / acceptance of results:
- - OTHER EFFECTS:
The mixture of 50 µL test item per 1 mL MTT medium showed no reduction of MTT as compared to the solvent. The mixture did not turn blue/purple. Therefore, NSMTT equalled 0%.
The mixture of 50 µL test item per 300 µL Aqua dest. and per 300 µL isopropanol showed no colouring as compared to the solvent. Therefore NSCliving equalled 0%.
DEMONSTRATION OF TECHNICAL PROFICIENCY: YES
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 for 3-minute experiment; NO for 60-minute experiment (coefficient of variation clearly exceeding the 30% threshold (66.2%)) - Interpretation of results:
- Category 1A (corrosive) based on GHS criteria
- Conclusions:
- The test item showed clearly corrosive effects. The mean relative tissue viability (% negative control) was reduced below 25% (17.6%) after 3 min treatment. Therefore, the test item will be classified as “corrosive”, optional sub-category 1A.
After 60 min treatment, mean tissue viability was reduced to 25.8%. The two tissues treated identically showed a high coefficient of variation, clearly exceeding the 30% threshold (66.2%). This is accepted since the 60 min treatment period has no impact on classification or sub-categorization of the test item. - Endpoint:
- skin irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- June-August 2017
- 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
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: MatTek Corporation Protocol for: In Vitro EpiDermTM Skin Irritation Test (EPI-200-SIT) For use with MatTek Corporation’s Reconstructed Human Epidermal Model EpiDerm (EPI-200-SIT); Version 07-Nov-2014
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Cell source:
- other: neonatal foreskin tissue or adult breast skin (single donor)
- Justification for test system used:
- The test uses the EpiDerm™ reconstructed human epidermis model (MatTek) which consists of normal human epidermal keratinocytes (NHEK) and therefore represents in vitro the target organ of the species of interest and closely mimics the biochemical and physiological properties of the upper parts of the human, i.e. the epidermis.
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- The test was carried out with the reconstituted three-dimensional human skin model EpiDermTM (MatTek). This skin model consists of normal human epidermal keratinocytes (NHEK) which have been cultured to form a multilayered, highly differentiated model of the human epidermis. The NHEK are cultured on chemically modified, collagen-coated cell culture inserts (Millicell). The EpiDermTM epidermis model exhibits in vivo-like morphological and growth characteristics which are uniform and highly reproducible. It consists of organised basal, spinous and granular layers and a multi-layered stratum corneum analogous to patterns found in vivo.
- Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- Negative control 30 µL DPBS
Positive control 30 µL 5% SDS solution
Test Item 30 µL (undiluted) - Duration of treatment / exposure:
- 60 +/- 1min
- Duration of post-treatment incubation (if applicable):
- 42 +/- 4 hrs
- Number of replicates:
- 3
- Irritation / corrosion parameter:
- % tissue viability
- Remarks:
- mean value of 3 replicates
- Value:
- 3.5
- 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:
- Preliminary experiment:
The mixture of 30 µL test item per 1 mL MTT medium showed no reduction of MTT compared to the solvent. The mixture did not turn blue/purple. Therefore, NSMTT equalled 0%.
The mixture of 30 µL of the test item per 300 µL aqua dest. and per 300 µL isopropanol showed no colouring detectable by unaided eye-assessment. Therefore, NSC equalled 0%. - Interpretation of results:
- Category 2 (irritant) based on GHS criteria
- Conclusions:
- In this study under the given conditions the test item showed irritant effects. The test item is therefore classified as “irritant” in accordance with UN GHS “Category 2”.
- Endpoint:
- skin corrosion: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- August 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 435 (In Vitro Membrane Barrier Test Method for Skin Corrosion)
- Version / remarks:
- 28 July 2015
- Deviations:
- no
- GLP compliance:
- yes
- Test system:
- artificial membrane barrier model
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- SOURCE AND COMPOSITION OF MEMBRANE BARRIER USED
- Was the Corrositex® test kit used: YES
- Components: biobarries membrane, chemical detection system
- Biobarrier preparation: A scintillation vial containing the biobarrier matrix powder was placed in a water bath on a stirring hot plate. The entire contents of the biobarrier diluent vial were added slowly to the matrix powder. The solution was warmed to 64-68ºC to solubilize the biobarrier matrix. Using a repeat pipettor 200 µL of the solubilized matrix solution were pipetted into each membrane disc. The membrane discs were then stored at 2-8ºC in a refrigerator overnight before being used for corrosivity testing.
- Assay: One rack of four scintillation vials containing the CDS was removed from the kit for the test article. One vial for the positive control, negative control, and color (blank) control were also removed. A membrane disc coated with the biobarrier matrix was placed into a vial containing the CDS. Then, 500 µL of the test article were added to the membrane disc. This vial was observed for three minutes for any change in the CDS. Since a color change was not detected within three minutes, these steps were repeated at one minute intervals, until the remaining membranes were treated with the test article. The vials were observed continuously for the first ten minutes and then at least at five minute intervals for up to 60 minutes (Category 2 test articles) or until a color change was detected. The first indication of the presence of the test article in the CDS was detected as a change in color, as compared to the blank control. The elapsed time required for this change to occur was recorded.
To test the positive control, a membrane disc coated with the biobarrier matrix was placed in a vial and one pellet of the positive control, sodium hydroxide (NaOH), was added to the membrane disc. This vial was monitored continuously until a breakthrough had occurred. To test the negative control, a membrane disc coated with the biobarrier matrix was placed in a vial and 500 µL of 10% Citric Acid were added to the membrane disc and observed periodically for 60 minutes to confirm that a breakthrough did not occur.
WAS THE COMPATIBILITY TEST PERFORMED: YES
For the qualification screen, 150 µL of the test article was added to the CDS qualification tube. The test article produced an immediate color change in the CDS, and was qualified for testing in the Corrositex® assay. Next, 100 µL of the test article was added to 1 mL of sterile, deionized water. The test article dilution was exposed to pH paper with a 0-14 pH range (EMD Millipore Corporation) with 1 pH unit increments to approximate a narrow pH range. Next, the test article dilution was exposed to pH paper with a narrower range of 5.0-10.0 pH units (EMD Millipore Corporation) with 0.5 pH unit increments, to obtain a more accurate pH value.
WAS THE TIMESCALE CATEGORY TEST PERFORMED: YES
The categorization screen was used to assess the test article's characteristics (such as acid or alkaline reserve) to allow it to be measured against the appropriate scoring scale. The screen was performed by adding 150 µL of the test article to each categorization screening tube (A and B). Each tube was mixed and the resulting color observed. The categorization kit and color chart provided by InVitro International was used to determine the category. Since a color change was not observed in tube A or B, two drops of the "confirm" reagent were added to tube B, mixed for five seconds, and the resulting color used to confirm the Category 2 designation.
TEMPERATURE USED DURING TREATMENT: ambient temperature
METHOD OF DETECTION
Corrositex®Chemical Detection System Supplied by InVitro International
METHOD OF APPLICATION: direct addition to the membrane disc
NUMBER OF REPLICATES: 4
NUMBER OF INDEPENDENT EXPERIMENTS TO DERIVE FINAL PREDICTION: 1
PREDICTION MODEL / DECISION CRITERIA - Category 2 chemical determined by the method's categorization test
- The test substance is considered to be corrosive to skin if less than 60 minutes elapsed between application of the test substance to the membrane barrier and barrier penetration.
- The test substance is considered to be non-corrosive to skin if more than 60 minutes elapsed between application of the test substance to the membrane barrier and barrier penetration.
- Justification for the selection of the cut-off point(s): Corrositex prediction model - Control samples:
- yes, concurrent negative control
- yes, concurrent no treatment
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 µL
NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 500 µL
- Concentration (if solution): 10%
POSITIVE CONTROL
- Amount(s) applied (volume or weight): one pellet - Duration of treatment / exposure:
- 60 minutes
- Number of replicates:
- 4 vials containing the CDS
- Irritation / corrosion parameter:
- penetration time (in minutes)
- Run / experiment:
- all 4 replicates
- Value:
- > 60
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: non-corrosive
- Other effects / acceptance of results:
- The results of the Categorization Screen (to assess acid or alkaline reserve) indicated that the test article fell into Category 2.
The test article was examined in a single trial (four replicates) to determine the mean breakthrough time and the appropriate packing group. A control (color blank) vial was included in the assay only for the purpose of comparison of the CDS color with the test article and positive control-treated samples. Therefore, no breakthrough result is reported for this vial. The results of the positive control, NaOH, fell within two standard deviations of the historical mean (acceptance range: 7:57 to 15:08 min:sec), and the negative control resulted in a non-corrosive response, thereby meeting the acceptance criteria. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- Based on the results of Corrositex assay, the test item is not skin corrosive.
- Executive summary:
Based on the results of Corrositex assay, the test item is not skin corrosive.
- Endpoint:
- skin corrosion: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- February-May 2019
- 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:
- 29 July 2016
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Justification for test system used:
- This in vitro method allows the identification of corrosive and non-corrosive substances and mixtures in accordance with UN GHS. It further allows a partial sub-categorisation of corrosives in optional sub-category 1A or a combination of optional sub-categories 1B and 1C.
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EpiDerm
- Tissue batch number(s): 28686
- Production date: 06.03.2019
- Date of initiation of testing: 1 March 2019
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 37 +/- 1°C
- Temperature of post-treatment incubation (if applicable): 37 +/- 1°C
REMOVAL OF TEST MATERIAL AND CONTROLS
- Number of washing steps: 20 times with PBS (phosphate buffered saline). Excess PBS was removed by gently shaking the insert and blotting bottom with blotting paper.
- Observable damage in the tissue due to washing: none
- Modifications to validated SOP: none
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: final 1 mg/mL
- Incubation time: 3 hrs
- Spectrophotometer: plate spectrophotometer
- Wavelength: 570 nm
NUMBER OF REPLICATE TISSUES: 2 per each experiment
NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: one 3-min experiment and one 60-min experiment
PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
- The test substance is considered to be corrosive to skin if the viability after 3 minutes exposure is less than 50%, or if the viability after 3 minutes exposure is greater than or equal to 50 % and the viability after 1 hour exposure is less than 15%.
- The test substance is considered to be non-corrosive to skin if the viability after 3 minutes exposure is greater than or equal to 50% and the viability after 1 hour exposure is greater than or equal to 15%. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50 µL (undiluted)
NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 50 µL distilled water
POSITIVE CONTROL
- Amount(s) applied (volume or weight): 50 µL 8 N KOH - Duration of treatment / exposure:
- 3 minutes and 60 minutes
- Duration of post-treatment incubation (if applicable):
- 3 hours with MTT, and then overnight wihout shaking or at least 2 hrs with shaking
- Number of replicates:
- 2 per each experiment (3-min and 60-min)
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 3-minute experiment mean value of 2 replicates
- Value:
- 83.6
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of irritation
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 60-minute experiment mean value of 2 replicates
- Value:
- 42.7
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of irritation
- Other effects / acceptance of results:
- 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:
- In this study under the given conditions the test item showed no corrosive effects. The test item is classified as “non-corrosive“.
- Endpoint:
- skin corrosion: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- February-May 2019
- 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:
- 29 July 2016
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Justification for test system used:
- This in vitro method allows the identification of corrosive and non-corrosive substances and mixtures in accordance with UN GHS. It further allows a partial sub-categorisation of corrosives in optional sub-category 1A or a combination of optional sub-categories 1B and 1C.
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EpiDerm
- Tissue batch number(s): 28686 (60-min), 28690 (3-min)
- Production date: 06.03.2019 (60-min), 03.04.2019 (3-min)
- Date of initiation of testing: 1 March 2019
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 37 +/- 1°C
- Temperature of post-treatment incubation (if applicable): 37 +/- 1°C
REMOVAL OF TEST MATERIAL AND CONTROLS
- Number of washing steps: 20 times with PBS (phosphate buffered saline). Excess PBS was removed by gently shaking the insert and blotting bottom with blotting paper.
- Observable damage in the tissue due to washing: none
- Modifications to validated SOP: none
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: final 1 mg/mL
- Incubation time: 3 hrs
- Spectrophotometer: plate spectrophotometer
- Wavelength: 570 nm
NUMBER OF REPLICATE TISSUES: 2 per each experiment
NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: one 3-min experiment and one 60-min experiment
PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
- The test substance is considered to be corrosive to skin if the viability after 3 minutes exposure is less than 50%, or if the viability after 3 minutes exposure is greater than or equal to 50 % and the viability after 1 hour exposure is less than 15%.
- The test substance is considered to be non-corrosive to skin if the viability after 3 minutes exposure is greater than or equal to 50% and the viability after 1 hour exposure is greater than or equal to 15%. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50 µL (undiluted)
NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 50 µL distilled water
POSITIVE CONTROL
- Amount(s) applied (volume or weight): 50 µL 8 N KOH - Duration of treatment / exposure:
- 3 minutes and 60 minutes
- Duration of post-treatment incubation (if applicable):
- 3 hours with MTT, and then overnight wihout shaking or at least 2 hrs with shaking
- Number of replicates:
- 2 per each experiment (3-min and 60-min)
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 3-minute experiment mean value of 2 replicates
- Value:
- 97.1
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of irritation
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 60-minute experiment mean value of 2 replicates
- Value:
- 51.9
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of irritation
- Other effects / acceptance of results:
- 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:
- In this study under the given conditions the test item showed no corrosive effects. The test item is classified as “non-corrosive“.
- Endpoint:
- skin irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- January-May 2019
- 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)
- Version / remarks:
- 28 July 2015
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Justification for test system used:
- This test uses the EpiDerm™ reconstructed human epidermis model (MatTek) which consists of normal human epidermal keratinocytes (NHEK) and therefore represents in vitro the target organ of the species of interest and closely mimics the biochemical and physiological properties of the upper parts of the human skin, i.e. the epidermis.
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EpiDerm™ (MatTek)
- Tissue batch number(s): 28680
- Delivery date: 23 January 2019
- Date of initiation of testing: 23 January 2019
TEMPERATURE USED FOR TEST SYSTEM
- Temperature of post-treatment incubation: 37 ± 1 °C
REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: 15 times washed with DPBS stream and then submerged in DPBS 3 times. Finally rinsed once with sterile DPBS.
- Observable damage in the tissue due to washing: none
- Modifications to validated SOP: none
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: final 1 mg/mL
- Incubation time: 3 h ± 5 min
- Spectrophotometer: plate
- Wavelength: 570 nm
- Filter bandwidth: ± 30 nm without reference wavelength
NUMBER OF REPLICATE TISSUES: 3
NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 1
PREDICTION MODEL / DECISION CRITERIA:
- The test substance is considered to be irritant to skin if the mean tissue viability amounts to <= 50% in comparision to negative control.
- The test substance is considered to be non-irritant to skin if the mean tissue viability amounts to > 50% in comparison to negative control. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 30 µL (undiluted)
NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 30 µL DPBS
POSITIVE CONTROL
- Amount(s) applied (volume or weight): 30 µL 5% SDS solution - Duration of treatment / exposure:
- 60 ± 1 min
- Duration of post-treatment incubation (if applicable):
- 24 ± 2 h and then 18 ± 2 h
- Number of replicates:
- 3
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 1
- Value:
- 3.1
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- positive indication of irritation
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 2
- Value:
- 4.2
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- positive indication of irritation
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 3
- Value:
- 3.6
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- positive indication of irritation
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- mean of 3 replicates
- Value:
- 3.6
- 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:
-
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:
- Category 2 (irritant) based on GHS criteria
- Conclusions:
- In this study under the given conditions the test item showed irritant effects. The test item is therefore classified as “irritant” in accordance with UN GHS “Category 2”.
- Endpoint:
- skin irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- January-May 2019
- 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)
- Version / remarks:
- 28 July 2015
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Justification for test system used:
- This test uses the EpiDerm™ reconstructed human epidermis model (MatTek) which consists of normal human epidermal keratinocytes (NHEK) and therefore represents in vitro the target organ of the species of interest and closely mimics the biochemical and physiological properties of the upper parts of the human skin, i.e. the epidermis.
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EpiDerm™ (MatTek)
- Tissue batch number(s): 28680
- Delivery date: 23 January 2019
- Date of initiation of testing: 23 January 2019
TEMPERATURE USED FOR TEST SYSTEM
- Temperature of post-treatment incubation: 37 ± 1 °C
REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: 15 times washed with DPBS stream and then submerged in DPBS 3 times. Finally rinsed once with sterile DPBS.
- Observable damage in the tissue due to washing: none
- Modifications to validated SOP: none
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: final 1 mg/mL
- Incubation time: 3 h ± 5 min
- Spectrophotometer: plate
- Wavelength: 570 nm
- Filter bandwidth: ± 30 nm without reference wavelength
NUMBER OF REPLICATE TISSUES: 3
NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 1
PREDICTION MODEL / DECISION CRITERIA:
- The test substance is considered to be irritant to skin if the mean tissue viability amounts to <= 50% in comparision to negative control.
- The test substance is considered to be non-irritant to skin if the mean tissue viability amounts to > 50% in comparison to negative control. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 30 µL (undiluted)
NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 30 µL DPBS
POSITIVE CONTROL
- Amount(s) applied (volume or weight): 30 µL 5% SDS solution - Duration of treatment / exposure:
- 60 ± 1 min
- Duration of post-treatment incubation (if applicable):
- 24 ± 2 h and then 18 ± 2 h
- Number of replicates:
- 3
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 1
- Value:
- 3.9
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- positive indication of irritation
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 2
- Value:
- 3
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- positive indication of irritation
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- 3
- Value:
- 2.9
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- positive indication of irritation
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- mean of 3 replicates
- Value:
- 3.3
- 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:
-
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:
- Category 2 (irritant) based on GHS criteria
- Conclusions:
- In this study under the given conditions the test item showed irritant effects. The test item is therefore classified as “irritant” in accordance with UN GHS “Category 2”.
Referenceopen allclose all
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:
- July-September 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)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Species:
- cattle
- Strain:
- not specified
- Details on test animals or tissues and environmental conditions:
- The assay uses isolated corneas obtained as a by-product from animals freshly slaughtered at the abattoir A. Moksel AG, Buchloe, Germany.
On the test day, fresh eyes were collected from the slaughterhouse and were transported in HBSS containing Pen/Strep on ice to the laboratories. Immediately after arrival of the eyes, cornea preparation was initiated.
The eyes were carefully examined for defects and any defective eyes were discarded. - Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent positive control
- yes, concurrent negative control
- Amount / concentration applied:
- 750 uL of the test substance or the control substances
- Duration of treatment / exposure:
- 10 minutes
- Observation period (in vivo):
- N/A
- Duration of post- treatment incubation (in vitro):
- 2 hours
- Number of animals or in vitro replicates:
- 3 corneas for the test item
3 corneas as negative controls treated with physiological saline 0.9% NaCl
3 corneas as positive controls treated with ethanol 100% - Details on study design:
- SELECTION AND PREPARATION OF CORNEAS
The tissue surrounding the eyeball was carefully pulled away and the cornea was excised leaving a 2 to 3 mm rim of sclera. The isolated corneas were stored in a petri dish containing HBSS. Before the corneas were mounted in corneal holders (Duratec GmbH) with the endothelial side against the O-ring of the posterior chamber, they had been visually examined for defects and any defective cornea had been discarded. The anterior chamber was then positioned on top of the cornea and tightened with screws. The chambers of the corneal holder were then filled with RPMI (without phenol red) containing 1% FBS and 2 mM L-glutamine (complete RPMI). The posterior chamber was always filled first. The corneas were incubated for one hour at 32 +/- 1 °C.
TREATMENT METHOD
After the equilibration period, the medium was removed from both chambers and replaced with fresh complete RPMI. An initial measurement was performed on each of the corneas using the opacitometer. Three corneas with illuminance readings approximately equivalent to the median illuminance of all corneas were selected as negative-control corneas. The illuminance of each cornea was read and recorded. Only corneas that had an initial illuminance reading I > I0/1.1651 lux were used for the assay. The medium was removed from the anterior chamber and replaced with the test item or control.
750 uL of the test substance or the control substance was introduced into the anterior chamber. As the viscosity of the test item was relatively high, it was applied directly onto the cornea by removing the window-locking ring and glass window prior to treatment. After 10 minutes incubation at 32 +/- 1 °C either the test substance or the control substance was removed and the epithelium washed at least three times with MEM (containing phenol red). Once the medium was free of test substance, the cornea was finally rinsed with complete RPMI (without phenol red). The anterior chamber was refilled with complete RPMI and an illuminance measurement was performed after 2 hours incubation at 32 +/- 1 °C. Also, each cornea was observed visually and pertinent observations were recorded.
After the illuminance measurement was performed, the medium was removed from both chambers of the holder. The posterior chamber was refilled with fresh complete RPMI.
1 mL of a 4 mg/mL sodium fluorescein solution was added to the anterior chamber and the corneas were incubated for 90 minutes at 32 +/- 1 °C. Then the medium from the posterior chamber was removed and its optical density at 490 nm (OD490) was determined, using a spectrophotometer (Jenway 6405 UV/VIS).
DECISION CRITERIA: as per OECD TG 437 - Irritation parameter:
- in vitro irritation score
- Run / experiment:
- mean value
- Value:
- 46.54
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation parameter:
- cornea opacity score
- Remarks:
- corrected opacity value
- Run / experiment:
- mean value
- Value:
- 10.47
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Irritation parameter:
- other: permeability
- Remarks:
- corrected OD490 value
- Run / experiment:
- mean value
- Value:
- 2.405
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- All 3 corneas treated with test item showed slight opacity of the tissue.
No prediction can be made regarding the classification of the test substance Strodex PK-90 according to the evaluation criteria. Further testing in another suitable method is required.
The in vitro irritation score obtained with the positive control fell within the two standard deviations of the current historical mean and therefore this assay is considered to be valid.
The negative control responses resulted in opacity and permeability values that are less than the established upper limits for background bovine corneas treated with the respective negative control. - Interpretation of results:
- other: No prediction can be made
- Remarks:
- 3 < IVIS <= 55
- Conclusions:
- No prediction can be made regarding the classification of the test substance according to the evaluation criteria.
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irreversible damage)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
The study for eye irritation potential did not show any conclusive results on eye corrosion. However, the substance tested positive in the skin corrosion test (category 1A) and therefore it is considered to cause irreversible damage also to eyes.
Justification for classification or non-classification
Skin corrosion category 1A and eye corrosion category 1 - based on OECD 431 test of product containing the substance at concentration above 67%.
Skin irritation category 2 based on OECD 431 and OECD 439 tests of products containing the substance at concentration below 67%.
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