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EC number: 265-019-0 | CAS number: 64690-19-3
- 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 vitro
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Experimental start date: 04 JULY 18, Experimental end date: 13 JULY18
- 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 442D (In Vitro Skin Sensitisation: ARE-Nrf2 Luciferase Test Method)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- activation of keratinocytes
Test material
- Reference substance name:
- N-octylpyridin-4-amine
- EC Number:
- 265-019-0
- EC Name:
- N-octylpyridin-4-amine
- Cas Number:
- 64690-19-3
- Molecular formula:
- C13H22N2
- IUPAC Name:
- N-octylpyridin-4-amine
Constituent 1
Results and discussion
In vitro / in chemico
Results
- Key result
- Remarks on result:
- no indication of skin sensitisation
Any other information on results incl. tables
Solubility Assessment
The testconcentrations ofN-Octyl-4-pyridinamine used in the KeratinoSens™methodwere selected onthe basisof solubilitytestcarried out duringthestudy:
Solubility ofthe test item inwas confirmedup to200mMin DMSO.Subsequentdilution incell culturemediumgave a top concentration of 2000μM.
Determination of the skin sensitisation potential of N-Octyl-4-pyridinamine
Determination criteria for the skin sensitisation potential of the test item
REP1 |
REP2 |
REP3 |
|
Does at least one concentration of Test Item induce luciferase activity ≥1.5-fold: |
No |
No |
No |
Does the first concentration inducing luciferase activity above 1.5, have a viability above 70%: |
N/A |
N/A |
N/A |
Is p value < 0.05 for at least one concentration that yielded ≥1.5-fold induction with viability above 70% |
N/A |
N/A |
N/A |
Does EC1.5 value occur at a concentration <1000μM (or <200μglml) |
N/A |
N/A |
N/A |
Does the test item induce the luciferase in a dose-dependent manner |
N/A |
N/A |
N/A |
Classification |
Negative |
Negative |
Negative |
Assay Acceptance Criteria (Mean of 3 repetitions)
Discussion
Thehumanskin sensitisation potential ofN-Octyl-4-pyridinaminewasassessedusing the validatedinvitromethod:the KeratinoSens™test todeterminekeratinocyte activation.Themethodwas adaptedtoanimal product-freeconditionsbyXCellR8 and reference chemicalsdescribedin theguideline and intheperformancestandards wereusedtoconfirmthereliability, accuracy,sensitivityandspecificityvalues.The adaptedmethodshowed fullconcordance with theValidated Reference Method (VRM)-theKeratinoSens™ standard protocol.XCellR8recentlyobtained clarification from theEuropean ChemicalsAgency (ECHA)thatdatausingthe adaptedmethodmaybeused in REACHsubmissions,providedthat thePerformanceStandards data, demonstratingequivalencewiththeVRM,areincludedin thedossier.
In thisstudy,N-Octyl-4-pyridinamine was classified asaNegativeusingtheKeratinoSens predictionmodel.Thesensitisationpotentialof thetestitemwas quantifiedbycalculating2 parameters known astheEC1.5andtheIMAXvalue:
•TheEC1.svalueistheEffectiveConcentration(EC) oftestitemthat yielded aninductionofluciferase activitygreater than1.5-foldoveruntreated controls.If atleastone concentrationinducesstatistically significant luciferase activity.≥1.5,thenthe productisclassified as positiveprovidedthe cellviability measured by MTT is greater than70%. Thetest item didnotinduce statisticallysignificantluciferaseinduction.≥1.5inany ofthe 3repetitions.The statisticalsignificance,viability,doseresponse and dose acceptancecriteria wereall met andtherefore:
The test itemwas classified asnegativeusing the KeratinoSens predictionmodel.
• The IMAX value is the maximum induction observed within theconcentrationrange tested.Although the KeratinoSens™ test is notvalidatedto predictpotency, theIMAXvalue canprovide a useful tool for preliminary comparison of sensitisationpotentialbetween test items.As shown in Section 13.2, the IMAXvalues for repetitions 1,2 and3were0.997 (0.977μM and 1.953 μM), 0.734 (1.953 μM) and 0.808(3.906 μM),respectively.Forreference, during testvalidation,sensitising proficiencychemicalsproduced IMAXvaluesofup to 36-fold over untreated controls.
All of the formal acceptance criteria of thetestswere met.
Solubility Assessment
The test concentrations of N-Octyl-4-pyridinamine used in the KeratinoSens™ 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 N-Octyl-4-pyridinamine
REP1 |
REP2 |
REP3 |
|
Does at least one concentration of Test Item induce luciferase activity ≥1.5-fold: |
No |
No |
No |
Does the first concentration inducing luciferase activity above 1.5, have a viability above 70%: |
N/A |
N/A |
N/A |
Is p value < 0.05 for at least one concentration that yielded ≥1.5-fold induction with viability above 70% |
N/A |
N/A |
N/A |
Does EC1.5 value occur at a concentration <1000μM (or <200μglml) |
N/A |
N/A |
N/A |
Does the test item induce the luciferase in a dose-dependent manner |
N/A |
N/A |
N/A |
Classification |
Negative |
Negative |
Negative |
Determination criteria for the skin sensitisation potential of the test item
Criteria | Result | PASS or FAIL | |
1 | Positive Control (PC) (Cinnamic aldehyde) induction ~1.5-fold in at least one concentration | 1.532 at 8.00 μM 1.842 at 16.00 μM 2.844 at 32.00 μM 3.996 at 64.00 μM 12.253 at 128.00 μM |
PASS |
2 | Average induction of PC at 32μM is [1.6-3.0) | 2.844 | PASS |
3 | EC1 .5 value is [6-39μM] | 7.1 74 μM | PASS |
4 | CV% of blank values < 20% | 9.551 | PASS |
Discussion
The human skin sensitisation potential of N-Octyl-4-pyridinamine was assessed using the validated in vitro method: the KeratinoSens™ test to determine keratinocyte activation. The method was adapted to animal product-free conditions by XCellR8 and reference chemicals described in the guideline and in the performance standards were used to confirm the re liability, accuracy, sensitivity and specificity values. The adapted method showed full concordance with the Validated Reference Method (VRM) - the KeratinoSens™ standard protocol. XCellR8 recently obtained clarification from the European Chemicals Agency (ECHA) that data using the adapted method may be used in REACH submissions, provided that the Performance Standards data, demonstrating equivalence with the VRM, are included in the dossier.
In this study, N-Octyl-4-pyridinamine was classified as a Negative using the KeratinoSens prediction model. The sensitisation potential of the test item was quantified by calculating 2 parameters known as the EC1.5and the IMAX value:
• The EC1.5value is the Effective Concentration (EC) of test item that yielded an induction of luciferase activity greater than 1.5-fold over untreated controls. If at least one concentration induces statistically significant luciferase activity .≥1.5, then the product is classified as positive provided the cell viability measured by MTT is greater than 70%. The test item did not induce statistically significant luciferase induction .≥1.5 in any of the 3 repetitions. The statistical significance, viability, dose response and dose acceptance criteria were all met and therefore:
The test item was classified as negative using the KeratinoSens prediction model.
• The IMAXvalue is the maximum induction observed with in the concentration range tested. Although the KeratinoSens™ test is not validated to predict potency, the IMAXvalue can provide a useful tool for preliminary comparison of sensitisation potential between test items. As shown in Section 13.2, the IMAXvalues for repetitions 1, 2 and 3 were 0.997 (0.977μM and 1.953 μM), 0.734 (1.953 μM) and 0.808 (3.906 μM), respectively. For reference, during test validation, sensitising proficiency chemicals produced IMAXvalues of up to 36-fold over untreated controls.
All of the formal acceptance criteria of the tests were met.
Applicant's summary and conclusion
- Interpretation of results:
- study cannot be used for classification
- Conclusions:
- After 48h exposure of cells with 12 concentrations of N-Octyl-4-pyridinamine, Luciferase measurements and MTT viability testing were performed.
N-Octyl-4-pyridinamine was classified as Negative according to the KeratinoSens prediction model.
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