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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 202-719-7 | CAS number: 98-98-6
- 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:
- 03 Nov - 09 Nov 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
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:
- February 2015
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Department of Health of the Government of the United Kingdom, Medicines & Healthcare products Regulatory Agency (MHRA), UK
- Type of study:
- direct peptide reactivity assay (DPRA)
Test material
- Reference substance name:
- Pyridine-2-carboxylic acid
- EC Number:
- 202-719-7
- EC Name:
- Pyridine-2-carboxylic acid
- Cas Number:
- 98-98-6
- Molecular formula:
- C6H5NO2
- IUPAC Name:
- pyridine-2-carboxylic acid
Constituent 1
In chemico test system
- Details on the study design:
- TEST METHOD
The DPRA is an in chemico test system proposed to address the molecular initiating event of the skin sensitisation adverse outcome pathway, namely protein reactivity, by substance towards model synthetic peptides containing either lysine or cysteine. The DPRA quantifies the free concentration of cysteine- or lysine-containing peptide following incubation with the test substance. Relative peptide concentration is measured by HPLC with gradient elution and UV detection at 220 nm. Cysteine- and lysine peptide percent depletion values are then calculated and used in the prediction model which allows assigning the test substance to one of four reactivity classes used to support the discrimination between sensitisers and non-sensitisers.
TEST SYSTEM
- Supplier: AnaSpec
- Synthetic cysteine-containing peptide:
Alternative name: Ac-RFAACAA-OH
Batch number: 1658140
- Purity: 98%
- Synthetic lysine-containing peptide:
Alternative name: Ac-RFAAKAA-OH
Batch number: 1556172
Purity: 94%
SOLVENT CONTROL AND ASSESSMENT OF TEST ITEM SOLUBILITY
- Solvent: distilled water: acetonitrile, 1:1 (v/v)
- Batch number: 1673078, Fisher Chemical
- Purity: ≥ 99.9%
The test substance was soluble in distilled water:acetonitrile, 1:1 (v/v) after mixing 5 min ultrasonification at 100 mM.
POSITIVE CONTROL
- Substance: cinnamic aldehyde
- Batch number: MKCB9907, SAFC
- Purity: 99.1%
The positive control chemical (cinnamic aldehyde) was prepared at a concentration of 100 mM in acetonitrile.
STABILITY AND PRECISION CONTROL
Stability, precision and co-elution controls were prepared.
PEPTIDE STOCK SOLUTION PREPARATION
Cysteine-containing peptide:
- Solvent: phosphate buffer (pH 7.5)
- Concentration: 0.667 mM
Lysine-containing peptide:
- Solvent: ammonium acetate buffer (pH 10.2)
- Concentration: 0.667 mM
INCUBATION CONDITIONS OF THE TEST SUBSTANCE WITH THE PEPTIDE SOLUTIONS
- Temperature used during treatment / exposure: 25 °C
- Duration of treatment / exposure: at least 22 h
NUMBER OF REPLICATES
triplicates for each peptide
HIGH PERFORMANCE LIQUID CHROMATOGRAPHY
- Specification of the device: Water Alliance 2695 separation module and 2487 dual wavelength detector
- Column: Agilent Zorbax SB C18, 3.5 µm, 100 x 2.1 mm with pre-column Phenomenex AJO4286
- HPLC mobile phase:
A: 0.1% (v/v) trifluoracetic acid in deionised water
B: 0.085% (v/v) trifluoracetic acid in acetonitrile
- Flow: 0.35 mL/min
- Gradient:
Time (min): 0, 20, 21, 23, 23.5, 30
% A: 90, 75, 10, 10, 90, 90
% B: 10, 25, 90, 90, 10, 10
- Detector Wavelength: 220 nm
- Calibration standard concentrations of both peptides: 0, 0.0167, 0.0334, 0.0667, 0.133, 0.267 and 0.534 mM.
- Column temperature: 30 °C
Results and discussion
- Positive control results:
- Mean Cysteine Peptide Depletion of the Positive control ± standard deviation (%): 70.7 ± 0.51
Individual and mean concentrations of the positive control are outside of the range established during the validation study. There is however considered to be no impact on the data reporting as both each individual and the overall mean depletion values are within the stated acceptance criteria of 60.8% - 100% depletion.
Mean Lysine Peptide Depletion of the Positive control ± standard deviation (%): 58.0 ± 0.55
In vitro / in chemico
Resultsopen allclose all
- Key result
- Run / experiment:
- other: Cysteine containing peptide
- Parameter:
- other: % depletion of peptide
- Remarks:
- (mean value of 3 replicates)
- Value:
- 0
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: Lysine containing peptide
- Parameter:
- other: % depletion of peptide
- Remarks:
- (mean value of 3 replicates)
- Value:
- 0.161
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Run / experiment:
- other: Cysteine/Lysine containing peptide
- Parameter:
- other: % Overall mean depletion of peptide
- Value:
- 0.081
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Remarks on result:
- no indication of skin sensitisation
- Other effects / acceptance of results:
- - There was no co-elution peaks in either of the Lysine or Cysteine assays.
- The solubility of the test substance in acetonitrile at a nominal concentration of 100 mM was confirmed.
ACCEPTANCE OF RESULTS:
All analytical acceptance criteria were met.
Any other information on results incl. tables
Table 3: The depletion of peptide in the presence of test substance
|
Mean peak area of reference control (µV.sec) |
Mean peak area of peptide with test item (µV.sec) |
Mean peptide depletion by test substance (%) |
Cysteine |
Control B: 847420 (n=6) |
856730 (n=3) |
-1.10 |
Lysine |
Control B: 764530 (n=6) |
763300 (n=3) |
0.161 |
Table 4: Overall Achieved Depletion Values
Test item |
Cysteine peptide depletion (%) |
Lysine peptide depletion (%) |
Overall mean depletion (%) |
Reactivity class |
DPRA prediction |
Test substance |
0.001* |
0.161 |
0.0805 |
None to minimal |
Negative |
* overall negative result counts as a zero
Table 5: Cysteine Peptide Depletion
Sample
|
Peak area (μV.sec) |
Peptide concentration1(μg/mL) |
Peptide Depletion2(%) |
Mean Depletion (%) |
SD (%) |
Positive control |
248527 |
110.9533 |
70.7 |
70.7 |
0.51 |
244193 |
109.0133 |
71.2 |
|||
252767 |
112.8533 |
70.2 |
|||
Test Substance |
857752 |
383.73 |
-1.22 |
- 1.10 |
0.13 |
856911 |
383.36 |
-1.12 |
|||
855537 |
382.74 |
-0.958 |
SD Standard Deviation
1 Samples prepared at a concentration of 376 μg/mL (0.5 mM)
2 Calculated against a mean Reference Control B area of 847420 μV.sec (n=6)
3 Individual and mean concentrations of the positive control are outside of the range established during the validation study. There is however considered to be no impact on the data reporting as both each individual and the overall mean depletion values are within the stated acceptance criteria of 60.8% - 100% depletion.
Table 6: Lysine Peptide Depletion
Sample
|
Peak area (μV.sec) |
Peptide concentration1(μg/mL) |
Peptide Depletion2(%) |
Mean Depletion (%) |
SD (%) |
Positive control |
316216 |
161.34 |
58.6 |
58.0 |
0.54 |
323723 |
165.19 |
57.7 |
|||
323072 |
164.86 |
57.7 |
|||
Test Substance |
761794 |
390.01 |
0.358 |
0.161 |
0.50 |
760485 |
389.33 |
0.529 |
|||
767620 |
392.99 |
-0.404 |
SD Standard Deviation
1 Samples prepared at a concentration of 388 μg/mL (0.5 mM)
2 Calculated against a mean Reference Control B area of 764530 μV.sec (n=6)
Applicant's summary and conclusion
- Interpretation of results:
- other: DPRA prediction: no skin sensitising potential based on the key event “protein reactivity”.
- Conclusions:
- The mean depletion of cysteine and lysine was 0.0805% (mean% depletion ≤ 6.38%).
Under the conditions of the Direct Peptide Reactivity Assay the test substance showed no or minimal peptide reactivity. No skin sensitising potential based on the key event “protein reactivity” is predicted.
The present test alone does not suit for the non-classification or classification of the test substance as skin sensitiser; further testings should be considered.
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.