Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
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: 700-296-8 | CAS number: 61337-89-1
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in chemico
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 24 January 2018 - 30 January 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- The validated in chemico skin sensitization test is the DPRA assay, which is recommended in international guidelines (e.g. OECD) and mentioned in the ECHA guidance as the in chemico test to be performed as part of weight of evidence.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 018
- Report date:
- 2018
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 442C (In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA))
- Version / remarks:
- 4 February 2015
- Deviations:
- no
- GLP compliance:
- yes
- Type of study:
- direct peptide reactivity assay (DPRA)
- Justification for non-LLNA method:
- A validated in chemico skin sensitization test is the DPRA assay, which is recommended in international guidelines (e.g. OECD) and mentioned in the ECHA guidance as one of the non-animal tests to be performed as part of weight of evidence.
Test material
- Reference substance name:
- {2-[(2R)-4-methyl-2-phenylpiperazin-1-yl]pyridin-3-yl}methanol; {2-[(2S)-4-methyl-2-phenylpiperazin-1-yl]pyridin-3-yl}methanol
- EC Number:
- 700-296-8
- Cas Number:
- 61337-89-1
- Molecular formula:
- C17-H21-N3-O
- IUPAC Name:
- {2-[(2R)-4-methyl-2-phenylpiperazin-1-yl]pyridin-3-yl}methanol; {2-[(2S)-4-methyl-2-phenylpiperazin-1-yl]pyridin-3-yl}methanol
- Test material form:
- solid: particulate/powder
- Details on test material:
- Physical appearance: white powder
Storage conditions: at room temperature
Constituent 1
In chemico test system
- Details on the study design:
- TEST ITEM PREPERATION
Solubility of the test item in an appropriate solvent was assessed before performing the DPRA. An appropriate solvent dissolved the test item completely, i.e. by visual inspection the solution had to be not cloudy nor have noticeable precipitate. The following solvent was evaluated: acetonitrile (ACN). Test item stock solutions were prepared freshly for each reactivity assay. For both the cysteine and lysine reactivity assay 48.59 mg of test item was pre-weighed into a clean amber glass vial and dissolved, just before use, in 1715 μL ACN to obtain a 100 mM solution. Visual inspection of the forming of a clear solution was considered sufficient to
ascertain that the test item was dissolved. The test item, positive control and peptide samples were prepared less than 4 hours before starting the incubation of the cysteine (cys) or lysine (lys) reactivity assay, respectively.
Synthetic peptides containing cysteine (SPCC) (Ac- RFAACAA-COOH) or synthetic peptides containing lysine (SPCL) (Ac-RFAAKAA-COOH). The molecular weight of SPCC is 750.9 g/mol, and 775.9 g/mol for SPCL. The peptides were stored in the freezer (<-15°C) for a maximum of 6 months.
- Source: JPT Peptide Technologies GmbH, Germany.
- Rationale: Recommended test system in the international OECD guideline for DPRA studies.
- Calibration curve SPCC and SPCL: according to guideline
- Incubation: After preparation, the samples (reference controls, calibration solutions, co-elution control, positive controls and test item samples) were placed in the autosampler, in the dark, and incubated at 25 ± 2.5°C. The incubation time between placement of the samples in the autosampler and analysis of the first RCcysB- or RClysB-sample was 25 hours. The time between the first RCcysB- or RClysB-injection and the last injection of a cysteine or lysine sequence, respectively, did not exceed 30 hours.
Prior to HPLC-PDA analysis the samples were visually inspected for precipitation.
- Analysis: All samples were analyzed according to the HPLC-PDA method presented in Table 1 ('Other information on methods and materials').
The HPLC sequences of the cysteine and lysine reactivity assay for the test item are presented in Table 2 ('Other information on materials and methods').
POSITIVE CONTROL: Cinnamic aldehyde
- Purity: 98.4%
- Batch: MKBP1014V
- Expiry of batch: 31 May 2018
DATA EVALUATION
The concentration of SPCC or SPCL was photometrically determined at 220 nm in each sample by measuring the peak area of the appropriate peaks by peak integration, and by calculating the concentration of peptide using the linear calibration curve derived from the standards.
The Percent Peptide Depletion was determined in each sample by measuring the peak area and dividing it by the mean peak area of the relevant reference controls C according to the following formula:
Percent Peptide Depletion = [1-(Peptide Peak Area in Replicate Injection (at 220 nm)/Mean Peptide Peak Area in Reference Controls (at 220 nm))]*100
In addition, the absorbance at 258 nm was determined in each sample by measuring the peak area of the appropriate peaks by peak integration. The ratio of the 220 nm peak area and the 258 nm peak was used as an indicator of co-elution. For each sample a ratio in the range of 90%< mean area ratio of control samples <110% gives a good indication that co-elution has not occurred.
DATA INTERPRETATION (see Table 3 'Other information on materials and method')
The mean Percent Cysteine Depletion and Percent Lysine Depletion were calculated for the test item. Negative depletion was considered as “0” when calculating the mean. By using the Cysteine 1:10 / Lysine 1:50 prediction model, the threshold of 6.38% average peptide depletion was used to support the discrimination between a skin sensitizer and a non-sensitizer.
Results and discussion
In vitro / in chemico
Resultsopen allclose all
- Key result
- Run / experiment:
- other: Cysteine Reactivity Assay
- Parameter:
- other: SPCC mean percentage
- Value:
- 1.2
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Remarks:
- CV between reference controls: 5.0%
- Positive controls validity:
- valid
- Remarks:
- Mean percentage SPCC: 79.3% ± 5.3%.
- Remarks on result:
- other: SD: 1.5%
- Run / experiment:
- other: Lysine Reactivity Assay
- Parameter:
- other: SPCL mean percentage
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- not valid
- Remarks:
- CV between reference controls: 38.5%
- Positive controls validity:
- valid
- Remarks:
- mean percentage SPCL: 68.1% ± 3.5%
- Remarks on result:
- other: Co-elution of the test item with SPCL, Therefore the depletion could not be determined
- Other effects / acceptance of results:
- Co-elution occured between the test item and SPCL.
See table 4 and 5 in " any other information on results incl. table" for results and acceptability of DPRA
Any other information on results incl. tables
Table 4: Acceptability of the Direct Peptide Reactivity Assay (DPRA)
|
Cysteine reactivity assay |
Lysine reactivity assay |
||
Acceptability criteria |
Results for SPCC |
Acceptability criteria |
Results for SPCL |
|
Correlation coefficient (r2) standard calibration curve |
>0.99 |
0.997 |
>0.99 |
0.998 |
Mean peptide concentration RC-A samples (mM) |
0.50 ± 0.05 |
0.507 ± 0.007 |
0.50 ± 0.05 |
0.496 ± 0.001 |
Mean peptide concentration RC-C samples (mM) |
0.50 ± 0.05 |
0.505 ± 0.008 |
0.50 ± 0.05 |
0.742 ± 0.293 |
CV (%) for RC samples B and C |
<15.0 |
5.0 |
<15.0 |
38.5 |
Mean peptide depletion cinnamic aldehyde (%) |
60.8-100 |
79.3 |
40.2-69.0 |
68.1 |
SD of peptide depletion cinnamic aldehyde (%) |
<14.9 |
5.3 |
<11.6 |
3.5 |
SD of peptide depletion for the test item (%) |
<14.9 |
1.5 |
<11.6 |
NA |
RC = Reference Control; CV = Coefficient of Variation; SD = Standard Deviation; NA = Not Applicable
Table 5: SPCC and SPCL Depletion, DPRA Prediction and Reactivity Classification for the Test Item
Test item |
SPCC depletion |
SPCL depletion |
DPRA prediction and reactivity classification |
|
Mean |
± SD |
Cysteine 1:10 prediction model |
||
HYDROPIP-NR |
1.2% |
±1.5% |
Co-elution |
Negative: No or minimal reactivity |
SD = Standard Deviation.
Applicant's summary and conclusion
- Interpretation of results:
- study cannot be used for classification
- Remarks:
- Study is part of a weight of evidence approach and is not used for classification on its own.
- Conclusions:
- HYDROPIP-NR was negative in the DPRA and was classified in the “no or minimal reactivity class” when using the Cysteine 1:10 prediction model.
- Executive summary:
A Direct Peptide Reactivity Assay (DPRA) was performed according to OECD TG 422C and in compliance with GLP. HYDROPIP-NR was dissolved in acetonitrile at 100 mM. Upon preparation as well as after incubation of the test item with synthetic peptides containing either cysteine (SPCC) or lysine (SPCL) no precipitate was observed. In the cysteine reactivity assay the test item showed 1.2% SPCC depletion. Co-elution was observed in the lysine reactivity assay and therefore SPCL depletion could not be calculated. Based on the results, HYDROPIP-NR was classified in the “no or minimal reactivity class” when using the Cysteine 1:10 prediction model and was considered to be negative in the DPRA.
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.