Registration Dossier
Registration Dossier
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 695-779-2 | CAS number: 80019-35-8
- 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
For OECD 442C, the final mean % depletion observed in the DPRA was 92.957%. Therefore, CR SR94 was classified as Positive with Moderate as per the Cysteine 1:10 prediction model.
For OECD 442D, the test item induced statistically significant luciferase induction >1.5 in all 3 repetitions. The respective EC1.5 values were calculated as 1.47 µM, 7.03 µM and 31.25 µM for repetitions 1 to 3 respectively. The statistical significance viability, dose response and dose acceptance criteria were all met. Therefore, the test item was classified as positive using the KeratinoSens prediction model.
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vitro
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From August 29, 2018 to June 14, 2019
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 442C (In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA))
- GLP compliance:
- yes
- Type of study:
- other: peptide depletion
- Justification for non-LLNA method:
- OECD 442C cites the DPRA model as a validated method for skin sensitization testing in the context of an integrated approach to testing and assessment.
- Details on the study design:
- Characterisation of the test method:
The DPRA has been evaluated in a European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM)-led validation study and subsequent independent peer review by the EURL ECVAM Scientific Advisory Committee (ESAC) and was considered scientifically valid to be used as part of an Integrated Approach to Testing and Assessment (IATA) to support the discrimination between skin sensitisers and non-sensitisers for the purpose of hazard classification and labelling.
Method workflow summary
Test items were incubated for 24 hours (±2hours) at 25±2.5°C in solution at 100mM in combination with either Cysteine or Lysine containing peptides and then run on an HPLC system (20-minute-runtime) using gradient elution and UV detection at 220nm to measure peptide concentration. Test items were compared to reference controls containing the test item solvent in combination with either Cysteine or Lysine peptide in order to determine the relative percent peptide depletion Relative percent peptide depletion values were used in a prediction model that assigns test items to one of four reactivity classes. - Run / experiment:
- other: 1
- Parameter:
- other: Cys % depletion
- Remarks:
- 1:10 Cysteine
- Value:
- 0.135
- Vehicle controls validity:
- valid
- Parameter:
- other: mean % depletion
- Remarks:
- Cysteine 1:10/lysine 1:50
- Value:
- 92.957
- Vehicle controls validity:
- valid
- Other effects / acceptance of results:
- All acceptance criteria were met in the Cysteine Run 1. However, multiple criteria for Lysine were not met in Run 2 (orange cells) and in addition there was significant co-elution of the test item, in the lysine peptide buffer. Hence the lysine data was not subsequently used and the Cysteine data and cysteine 1:10 prediction model alone were used.
- Interpretation of results:
- Category 1 (skin sensitising) based on GHS criteria
- Conclusions:
- The final mean %peptide depletion observed in the DPRA was 92.957%. Therefore, CR SR94 was classified as Positive with Moderate as per the Cysteine 1:10 prediction model.
- Executive summary:
In this study, the skin sensitization potential of CR SR94 was assessed using the In Chemico Direct Peptide Reactive Assay (DPRA) method according to OECD442C. After a 24h incubation with both Cysteine and Lysine containing peptides, the percent peptide depletion was measured by High Performance Liquid Chromatography (HPLC).
For assessment of CR SR94 the Cysteine peptide 1:10 prediction model was used. The final mean % peptide depletion observed using this model was 92.957%. Therefore, CR SR94 was classified as Positive with Moderate reactivity as per the prediction model.
- Endpoint:
- skin sensitisation: in vitro
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From August 16, 2018 to April 30, 2019
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 442D (In Vitro Skin Sensitisation: ARE-Nrf2 Luciferase Test Method)
- GLP compliance:
- yes
- Type of study:
- other: immotalized adherent cell line derived from HaCaT human keratinocytes
- Details on the study design:
- Preliminary testing: Determination of the top concentration by solubility testing
Day 1: Cell seeding (3 x 96-well plates for Luminescence; 2 x 96-well plate for MTT); 10,000 cells per well, passage number 17.
Day 2: 24 hours after seeding, the test and control items were applied and plates were incubated at 37°C, 5% CO2, ≥95% relative humidity for 48±2 hours.
Day 4: Evaluation of luciferase activity by luminescence (3 plates) and cell viability by MTT testing (2 plates). - Run / experiment:
- other: 1
- Parameter:
- other: EC1.5 value
- Remarks:
- µM
- Value:
- 1.47
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- positive indication of skin sensitisation
- Run / experiment:
- other: 2
- Parameter:
- other: EC1.5 value
- Remarks:
- µM
- Value:
- 7.03
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- positive indication of skin sensitisation
- Run / experiment:
- other: 3
- Parameter:
- other: EC1.5 value
- Remarks:
- µM
- Value:
- 31.25
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- positive indication of skin sensitisation
- Interpretation of results:
- Category 1 (skin sensitising) based on GHS criteria
- Conclusions:
- The test item induced statistically significant luciferase induction >1.5 in all 3 repetitions. The respective EC1.5 values were calculated as 1.47 µM, 7.03 µM and 31.25 µM for repetitions 1 to 3 respectively. The statistical significance viability, dose response and dose acceptance criteria were all met. Therefore, the test item was classified as positive using the KeratinoSens prediction model.
- Executive summary:
The human skin sensitisation potential of CR SR94 was assessed using the validated in vitro method, the KeratinoSens TM assay, adapted to animal product-free conditions by XCellR8, and validated in-house to determine keratinocyte activation.
After 48h exposure of cells with 12 concentrations of CR SR94, Luciferase measurements and MTT viability testing were performed.
CR SR94 was classified as Positive according to the KeratinoSens prediction model.
Referenceopen allclose all
Table 1. Acceptance criteria of Cysteine and Lysine
Criterion | Run 1 (Cysteine) |
Run 2 (Lysine) |
Outcome |
Std Curve r^2>0.99 | 0.993 | 0.988 | PASS/FAIL |
PC 60.8% to 100% depletion Cys | 69.689% | N/A | PASS |
PC 40.2% to 69.4% depletion Lys | N/A | 5.555% | FAIL |
SD Cys Depletion PC<14.9% | 0.437% | N/A | PASS |
SD Lys Depletion PC<11.6% | N/A | No Data | FAIL |
RefA Mean Conc 0.50±0.05mM | 0.523 M | 0.515 mM | PASS/PASS |
Peak Area CV RefB<15.0% | 1.661% | 77.573% | PASS/FAIL |
Peak Area CV RefC<15.0% | 0.552% | 173.205% | PASS/FAIL |
SD Cys Depletion Test Item<14.9% | 0.135% | N/A | PASS |
SD Lys Depletion Test Item<11.6% | N/A | 1.795% | PASS |
RefC Mean Conc 0.50±0.05mM | 0.524 mM | 0.184 mM | PASS/FAIL |
Cys = Cysteine, Lys = Lysine, SD = Standard Deviationm CV = Coefficient of Variation, PC = Positive Control.
Note that standard 2 and standard 7 for Cysteine was excluded from the standard curve as they were outlier values. The standard curve was produced successfully using the remaining 5 points, therefore there was no impact upon the final data.
Solubility Assessment
The test concentrations of CR SR94 used in the KeratinoSens TM method were selected on the basis of solubility test carried out during the study:
Solubility of the test item in was confirmed up to 200mM in DMSO. Subsequent dilution in cell culture medium gave a top concentration of 2000µM.
Determination of the skin sensitisation potential of CR SR94
Table 1. Sensitisation Potential of the Test Item: Repetition 1
Repetition 1 | Test item concentration (µM) | |||||||||||
0.98 | 1.95 | 3.91 | 7.81 | 15.63 | 31.25 | 62.50 | 125.00 | 250.00 | 500.00 | 1000.00 | 2000.00 | |
Mean fold induction | 1.007 | 1.987 | 1.793 | 1.767 | 1.785 | 1.951 | 2.067 | 2.053 | 2.366 | 5.255 | 64.448 | 0.060 |
Viability% | 242.951 | 103.104 | 101.248 | 96.697 | 77.872 | 95.418 | 99.617 | 93.515 | 88.35 | 85.518 | 78.605 | 7.929 |
T-test | 9.29E-01 | 9.14E-08 | 1.10E-08 | 7.22E-11 | 8.80E-13 | 1.68E-14 | 2.61E-18 | 5.12E-18 | 7.70E-22 | 8.70E-41 | 8.13E-32 | 1.41E-17 |
SD | 0.099 | 1.021 | 0.654 | 0.418 | 0.280 | 0.378 | 0.238 | 0.244 | 0.319 | 0.614 | 18.226 | 0.034 |
Imax | 64.448 at 1000µM | |||||||||||
EC1.5 | 1.47µM | |||||||||||
IC30 | 1121.75µM | |||||||||||
IC50 | 1404.73µM |
Table 2. Sensitisation Potential of the Test Item: Repetition 2
Repetition 2 | Test item concentration (µM) | |||||||||||
0.98 | 1.95 | 3.91 | 7.81 | 15.63 | 31.25 | 62.50 | 125.00 | 250.00 | 500.00 | 1000.00 | 2000.00 | |
Mean fold induction | 0.881 | 1.131 | 0.989 | 1.628 | 2.076 | 1.35 | 1.249 | 1.191 | 0.844 | 1.773 | 5.917 | 0.002 |
Viability% | 116.410 | 129.377 | 138.189 | 140.778 | 136.881 | 122.87 | 120.811 | 118.448 | 95.299 | 73.029 | 29.512 | 7.094 |
T-test | 1.37E-01 | 9.12E-02 | 9.00E-01 | 1.54E-09 | 5.36E-13 | 7.39E-05 | 3.66E-03 | 1.87E-02 | 4.85E-02 | 8.27E-13 | 1.64E-29 | 1.08E-18 |
SD | 0.167 | 0.066 | 0.288 | 0.307 | 0.623 | 0.222 | 0.232 | 0.159 | 0.112 | 0.255 | 1.473 | 0.003 |
Imax | 5.917 at 1000µM | |||||||||||
EC1.5 | 7.03µM | |||||||||||
IC30 | 534.80µM | |||||||||||
IC50 | 764.60µM |
Table 3. Sensitisation Potential of the Test Item: Repetition 3
Repetition 3 | Test item concentration (µM) | |||||||||||
0.98 | 1.95 | 3.91 | 7.81 | 15.63 | 31.25 | 62.50 | 125.00 | 250.00 | 500.00 | 1000.00 | 2000.00 | |
Mean fold induction | 0.937 | 1.060 | 1.129 | 1.376 | 1.394 | 1.500 | 1.741 | 1.783 | 1.753 | 2.021 | 12.944 | 4.095 |
Viability% | 122.173 | 124.664 | 135.718 | 130.892 | 121.706 | 141.866 | 126.699 | 132.592 | 140.955 | 126.376 | 114.69 | 38.931 |
T-test | 4.16E-01 | 4.32E-01 | 1.03E-01 | 1.22E-05 | 4.43E-06 | 6.83E-08 | 1.62E-12 | 3.95E-14 | 1.99E-12 | 6.03E-16 | 1.83E-43 | 3.93E-14 |
SD | 0.108 | 0.052 | 0.134 | 0.142 | 0.117 | 0.193 | 0.223 | 0.123 | 0.255 | 0.359 | 1.980 | 0.221 |
Imax | 12.944 at 1000µM | |||||||||||
EC1.5 | 31.25µM | |||||||||||
IC30 | 1589.90µM | |||||||||||
IC50 | 1853.89µM |
Dtermination criteria for the skin sensitisation potential of the test item
REP 1 | REP 2 | REP 3 | |
Does at least one concentration of Test Item induce luciferase activity≥1.5-fold? | Yes | Yes | Yes |
Does the first concentration inducing luciferase activity equal to or above 1.5, have a viability above 70%? | Yes | Yes | Yes |
Is p value<0.05 for at least one concentration that yielded≥1.5-fold induction with viability above 70%? | Yes | Yes | Yes |
Does EC1.5 value occur at a concentration <1000µM (<200µg/mL) | Yes | Yes | Yes |
Does the test item induce the luciferase in a dose-dependent manner? | Yes | Yes | Yes |
Classification | Positive | Positive | Positive |
Assay Acceptance Criteria (Mean of 3 repetitions)
Criteria | Result | PASS or FAIL | |
1 | Positive Control (PC) (Cinnamic aldehyde) induction≥1.5-fold in at least one concentration | Yes (4/5) | PASS |
2 | Average induction of PC at 32µM is [1.6~3.0] | Yes (2.161) | PASS |
3 | EC1.5 value is [6-39µM] | Yes (14.024µM) | PASS |
4 | CV% of blank values <20% | Yes (10.1038%) | PASS |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (sensitising)
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Skin sensitisers shall be classified in Category 1 where data are not sufficient for sub-categorisation.
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.
