N-octylpyridin-4-amine

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

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

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

Key result

Remarks on result:

no indication of skin sensitisation

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 astheEC1.5andtheI_MAXvalue:

•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 I_MAXvalues 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 I_MAXvaluesofup 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 EC_1.5and the IMAX value:

• The EC_1.5value 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 I_MAXvalue is the maximum induction observed with in the concentration range tested. Although the KeratinoSens™ test is not validated to predict potency, the I_MAXvalue can provide a useful tool for preliminary comparison of sensitisation potential between test items. As shown in Section 13.2, the I_MAXvalues 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 I_MAXvalues of up to 36-fold over untreated controls.

All of the formal acceptance criteria of the tests were met.

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.

Reference 2

Endpoint:

skin sensitisation: in chemico

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Experimental start date 05 June 2018, Experimental completion date 08 June 2018

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))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

direct peptide reactivity assay (DPRA)

Details on the study design:

Peptide and Positive Control
Synthetic peptide containing Cysteine
Alternative name: Ac-RFAACAA-OH
Batch number: 1658140
Stated purity: 97.8% (by HPLC)
Molecular Weight: 751 g/mol
Supplier: AnaSpec
Storage conditions: Frozen (-10°C to -30°C)

Synthetic peptide containing Lysine
Alternative name: Ac-RFAAKAA-OH
Batch number: 1658141
Stated purity: 96.8% (by HPLC)
Molecular Weight: 776 g/mol
Supplier: AnaSpec
Storage conditions: Frozen (-10°C to -30°C)

Cinnamic Aldehyde (Positive control)
Batch number: MKCB9907
Stated purity: 99.1%
Molecular Weight: 132 g/mol
Supplier: SAFC
Storage conditions: Room temperature (15°C to 25°C)
Expiry/retest date: November 2021

Apparatus
High performance liquid
chromatograph (HPLC):
Waters Alliance 2695 separation module and 2487
dual wavelength detector
Balances fitted with printers: Capability of weighing to 5 decimal places
General laboratory apparatus and glassware.

Analytical Procedure
Reagents
Acetonitrile (ACN): HPLC gradient grade
Trifluoroacetic acid (TFA): 99% Pure
Water: Deionised reverse osmosis
Ammonium Acetate: Analytical reagent
Sodium Phosphate, monobasic: Analytical reagent
Sodium Phosphate, dibasic: Analytical reagent
Ammonium Hydroxide: Analytical reagent
100 mM Phosphate buffer, pH 7.5: In house preparation
100 mM Ammonium Acetate buffer, pH 10.2: In house preparation
HPLC Mobile Phase A: 0.1% v/v TFA in Water, in house preparation
HPLC Mobile Phase B: 0.085% v/v TFA in ACN, in house preparation

Preparation of Peptide Stock Solutions
Stock solutions of each peptide at concentrations of 0.667 mM were prepared by dissolution of pre-weighed aliquots of the appropriate peptide in ca 20 mL aliquots of the appropriate buffer solution (Cysteine in 100 mM phosphate buffer pH 7.5, Lysine in 100 mM Ammonium acetate buffer pH 10.2).

Preparation of Peptide Calibration Standards
Calibration standards of both peptides were prepared by diluting the requisite stock solution in the appropriate buffer and acetonitrile and contained each peptide at concentrations of 0.0167 mM, 0.0334 mM, 0.0667 mM, 0.133 mM, 0.267 mM and 0.534 mM. A buffer blank was also prepared.

Preparation of Stability Controls and Precision Controls
Precision controls (Reference Control A) and stability controls (Reference Control B) of both peptides were prepared at a peptide concentration of 0.5 mM in buffer and acetonitrile.

Preparation of Positive Control Solution and Test Item Stock Solution
The positive control chemical (Cinnamic Aldehyde) was prepared at a concentration of 100 mM in acetonitrile. A 100 mM stock solution of N-octyl-4-pyridinamine was prepared in acetonitrile.

Preparation of Positive Control and Cysteine Peptide Depletion Samples and Co-elution Controls
Accurate volume aliquots of N-octyl-4-pyridinamine and the positive control were diluted with the Cysteine peptide stock solution to prepare solutions containing 0.5 mM Cysteine and 5 mM of either N-octyl-4-pyridinamine or the positive control. For the co-elution control, buffer solution was used in place of the Cysteine stock solution.

Preparation of Positive Control and Lysine Peptide Depletion Samples and Co-elution Controls
Accurate volume aliquots of N-octyl-4-pyridinamine and the positive control were diluted with the Lysine peptide stock solution to prepare solutions containing 0.5 mM Lysine and 25 mM of either N-octyl-4-pyridinamine or the positive control. For the co-elution control, buffer solution was used in place of the Lysine stock solution.

Incubation
The appearance of the N-octyl-4-pyridinamine and positive control samples in the HPLC vials was documented after preparation and then the vials placed into the autosampler of the HPLC set at 25°C for a minimum of 22 hours incubation prior to injection of the samples as part of analytical run. Before initiation of the run the appearance of the samples in the vials was assessed and documented again.

Analysis
The concentration of both the Cysteine and Lysine peptides in the presence of N-octyl-4-pyridinamine and the associated positive controls was quantified by HPLC using UV detection as detailed in the chromatographic section.

Instrumentation Parameters
High performance liquid
chromatograph (HPLC):
Waters Alliance 2695 separation module and
2487 dual wavelength detector
Column: Agilent Zorbax SB C18, 3.5µm, 100 x 2.1 mm
Guard column: Phenomenex AJO4286
Column temperature: 30°C
Sample temperature: 25°C
Mobile Phase (MP) A: 0.1% TFA in Water
Mobile Phase (MP) B: 0.085% TFA in ACN
Gradient:
0min MP - A:90% B:10%
20min MP - A:75% B:25%
21min MP - A:10% B:90%
23min MP - A:10% B:90%
23.5min MP - A:90% B:10%
30min MP - A:90% B:10%

Flow rate: 0.35 mL/minute
Stroke volume 25 µL
Detector wavelength: UV, 220 nm
Injection volume: 2 µL (slow draw rate)
Run time: 30 minutes
Approximate retention time (Cysteine) 11 minutes
Approximate retention time (Lysine) 7 minutes

Calculations
The peak area response for the peptide in each calibration chromatogram was measured. Calibration curves were constructed by linear regression of standard response versus standard concentration. The area responses of the peptide peak observed at the characteristic retention time of each peptide in each sample chromatogram was measured. Peptide depletion was determined using the following equation:

% Peptide depletion =
100 - ((Peptide peak area in replicate depletion samples x 100) / Mean Peptide peak area of reference control samples B)

Key result

Parameter:

other: Cysteine depletion (%)

Value:

-0.219

Key result

Parameter:

other: Lysine depletion (%)

Value:

-1.44

Interpretation of results:

study cannot be used for classification

Conclusions:

Solutions of N-octyl-4-pyridinamine were successfully analyzed by the validated DPRA analytical method (Envigo analytical method FIA/M101/15) in both Cysteine and Lysine containing synthetic peptides. There was no reactivity in both peptides and therefore N-octyl-4-pyridinamine is placed in the reactivity class of “no or minimal” and hence it is predicted by DPRA to be negative in terms being a potential skin sensitizer.

Reference 3

Endpoint:

skin sensitisation, other

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

DEREK (skin sensitisation)
1 Substance
1.1 CAS number 64690-19-3
1.2 EC number 265-019-0
1.3 Chemical name
IUPAC N-Octyl-4-pyridinamine
Other
Other
1.4 Structural formula

1.5 Structure codes
SMILES CCCCCCCCNC1=CC=NC=C1
InChI InChI=1S/C13H22N2/c1-2-3-4-5-6-7-10-15-13-8-11-14-12-9-13/h8-9,11-12H,2-7,10H2,1H3,(H,14,15)
Other
Stereochemical features Not applicable

2 General Information
2.1 Date of QPRF 21 February 2019
2.2 Author and contact details Envigo, Shardlow Business Park
London Road, Shardlow, Derbyshire, DE72 2GD

3 Prediction
3.1 Endpoint (OECD Principle 1)
Endpoint Skin Sensitisation
Dependent variable Not applicable
3.2 Algorithm (OECD Principle 2)
Model or submodel name Skin sensitisation in mammal
Model version DEREK Nexus 5.0.2, Nexus: 2.1.1.
Knowledge Base: Derek KB 2018 1.1, Version 1.1 from 23/11/2017
Reference to QMRF The QMRF with the identifier Q13-34-36-315 is available from the JRC QMRF inventory (http://qsardb.jrc.it/qmrf/).
Predicted values (model result) No alerts
Predicted values (comments) Skin sensitisation in mammal is NON-SENSITISER (Contains misclassified features)

Input for prediction Smiles
Calculated descriptor values Descriptor Value
LogP 4.82
LogKp -0.56

3.3 Applicability domain (OECD Principle 3)
Domains The parameters that have influenced the prediction are: substructures in the input structure, which have the potential to cause skin sensitisation; your selected species, which is mammal.

Features of the query structure (highlighted in the structure panel) were found in the Lhasa skin sensitisation negative prediction dataset and have been observed in sensitisers that do not match skin sensitisation structural alerts in Derek. The relationship between these features and skin sensitisation may be coincidental or contributory. However, as the query structure does not match any structural alerts or examples for skin sensitisation in Derek, it is predicted to be a non-sensitiser.

Structural analogues
Standardised structure Structure ID Assay Type Assay Result Reference(s)
Structure-1022 GPMT POSITIVE (1) Magnusson B, Kligman AM, Journal of Investigative Dermatology, 1969, 52, 268-276
Structure-1022 Draize test POSITIVE
Consideration on structural analogues
The compound referred to by the software relating to this potentially misclassified feature does include the 4-pyridinamine moiety, but the molecule is also characterised by several other functionalities. The negative prediction is substantiated by the lack of an identified skin sensitisation alert triggered in the OECD toolbox. Furthermore, assessment of the Structure-1022 via toolbox identifies several metabolites with alerts and alerts in the parent structure which are not shared with the target structure. Lending weight to the negative prediction.
3.4 The uncertainty of the prediction (OECD principle 4)
Skin sensitisation in mammal is NON-SENSITISER (Contains misclassified features)
The model identifies a potential alert from a misclassified feature in the dataset. Which would disagree with the conclusion. However, no alerts were identified in other assessed models.
3.5 The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5)
The query structure does not match any structural alerts or examples for skin sensitisation in Dereks knowledge base. The misclassified feature identified has been discounted as explained above, consequently predicted to be a non-sensitizer.

4 Adequacy (Optional)
4.1 Regulatory purpose Skin sensitisation endpoint for assessing the skin sensitisation potential with in vitro and in silico methods according to ECHA Guidance, Chapter R.7a, 2016.

4.2 Approach for regulatory interpretation of the model result
Result is directly applicable since no conversion of the result is required.

4.3 Outcome Skin sensitisation in mammal is NON-SENSITISER (No misclassified or unclassified features).
The predictive performance of this alert is considered to be moderate (for details, see software printout). DEREK alert is substantiated by the lack of an identified skin sensitisation alert triggered in the OECD toolbox, and the corresponding presence of alerts for the substance identified in Derek.

4.4 Conclusion Non-sensitizer.

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: QSAR prediciton of Skin senistisation
- Short description of test conditions: n/a
- Parameters analysed / observed: Skin senistisation

Remarks on result:

no indication of skin sensitisation

DEREK (skin sensitisation)

1

Substance

1.1

CAS number

64690-19-3

1.2

EC number

265-019-0

1.3

Chemical name

IUPAC

N-Octyl-4-pyridinamine

Other

Other

1.4

Structural formula

1.5

Structure codes

SMILES

CCCCCCCCNC1=CC=NC=C1

InChI

InChI=1S/C13H22N2/c1-2-3-4-5-6-7-10-15-13-8-11-14-12-9-13/h8-9,11-12H,2-7,10H2,1H3,(H,14,15)

Other

Stereochemical features

Not applicable

2

General Information

2.1

Date of QPRF

21 February 2019

2.2

Author and contact details

Envigo, Shardlow Business Park London Road, Shardlow, Derbyshire, DE72 2GD

3

Prediction

3.1

Endpoint (OECD Principle 1)

Endpoint

Skin Sensitisation

Dependent variable

Not applicable

3.2

Algorithm (OECD Principle 2)

Model or submodel name

Skin sensitisation in mammal

Model version

DEREK Nexus 5.0.2, Nexus: 2.1.1. Knowledge Base: Derek KB 2018 1.1, Version 1.1 from 23/11/2017

Reference to QMRF

The QMRF with the identifier Q13-34-36-315 is available from the JRC QMRF inventory (http://qsardb.jrc.it/qmrf/).

Predicted values (model result)

No alerts

Predicted values (comments)

Skin sensitisation in mammal is NON-SENSITISER (Contains misclassified features)

Input for prediction

Smiles

Calculated descriptor values

Descriptor Value LogP 4.82 LogKp -0.56

3.3

Applicability domain (OECD Principle 3)

Domains

The parameters that have influenced the prediction are: substructures in the input structure, which have the potential to cause skin sensitisation; your selected species, which is mammal. Features of the query structure (highlighted in the structure panel) were found in the Lhasa skin sensitisation negative prediction dataset and have been observed in sensitisers that do not match skin sensitisation structural alerts in Derek. The relationship between these features and skin sensitisation may be coincidental or contributory. However, as the query structure does not match any structural alerts or examples for skin sensitisation in Derek, it is predicted to be a non-sensitiser.

Structural analogues

Standardised structure

Structure ID

Assay Type

Assay Result

Reference(s)

Structure-1022

GPMT

POSITIVE

(1) Magnusson B, Kligman AM, Journal of Investigative Dermatology, 1969, 52, 268-276

Structure-1022

Draize test

POSITIVE

Consideration on structural analogues

The compound referred to by the software relating to this potentially misclassified feature does include the 4-pyridinamine moiety, but the molecule is also characterised by several other functionalities. The negative prediction issubstantiated by the lack of an identified skin sensitisation alert triggered in the OECD toolbox. Furthermore, assessment of the Structure-1022 via toolbox identifies several metabolites with alerts and alerts in the parent structure which are not shared with the target structure. Lending weight to the negative prediction.

3.4

The uncertainty of the prediction (OECD principle 4)

Skin sensitisation in mammal is NON-SENSITISER (Contains misclassified features) The model identifies a potential alert from a misclassified feature in the dataset. Which would disagree with the conclusion. However, no alerts were identified in other assessed models.

3.5

The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5)

The query structure does not match any structural alerts or examples for skin sensitisation in Dereks knowledge base. The misclassified feature identified has been discounted as explained above, consequently predicted to be a non-sensitizer.

4

Adequacy (Optional)

4.1

Regulatory purpose

Skin sensitisation endpoint for assessing the skin sensitisation potential with in vitro and in silico methods according to ECHA Guidance, Chapter R.7a, 2016.

4.2

Approach for regulatory interpretation of the model result

Result is directly applicable since no conversion of the result is required.

4.3

Outcome

Skin sensitisation in mammal is NON-SENSITISER (No misclassified or unclassified features). The predictive performance of this alert is considered to be moderate (for details, see software printout). DEREK alert is substantiated by the lack of an identified skin sensitisation alert triggered in the OECD toolbox, and the corresponding presence of alerts for the substance identified in Derek.

4.4

Conclusion

Non-sensitizer.

Interpretation of results:

GHS criteria not met

Conclusions:

Outcome
Skin sensitisation in mammal is NON-SENSITISER (No misclassified or unclassified features).
The predictive performance of this alert is considered to be moderate (for details, see software printout). DEREK alert is substantiated by the lack of an identified skin sensitisation alert triggered in the OECD toolbox, and the corresponding presence of alerts for the substance identified in Derek.

Conclusion
Non-sensitizer.

Reference 4

Endpoint:

skin sensitisation, other

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

1. SOFTWARE
QSAR Toolbox 4.2

2. MODEL (incl. version number)
QSAR Toolbox 4.2
Database version: 4.2
TPRF v4.2

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CCCCCCCCNC1=CC=NC=C1

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
[Explain how the model fulfils the OECD principles for (Q)SAR model validation. Consider attaching the QMRF or providing a link]
see attached justificaiton

5. APPLICABILITY DOMAIN
[Explain how the substance falls within the applicability domain of the model]
see attached ustification

6. ADEQUACY OF THE RESULT
[Explain how the prediction fits the purpose of classification and labelling and/or risk assessment]
Prediction is considered to be reliable since the nearest neighbours are of moderate (>50%) similarity to the target, and while the mechanism is ill defined, there is concordance within the category substances which provides some confidence in the prediction.

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: QSAR prediciton of Skin senistisation
- Short description of test conditions: n/a
- Parameters analysed / observed: Skin senistisation

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

GHS criteria not met

Conclusions:

Prediction using the profilers mentioned above for the OECD QSAR Toolbox suggested the material may indeed be non-sensitizing. A prediction was possible to be made using Protein binding alerts for skin sensitisation by oasis as the primary grouping, further then subcategorised using protein binding alerts for skin sensitization by oasis with skin metabolism and autoxidation simulator, chemical elements, and structural similarity. The prediction result was negative, with four out of the five nearest compounds being negative, with said compounds having an average similarity to the target of 54.4% which is considered moderate. Despite the profilers for sensitisation being used was “no alert found”, one of the returned similar compounds displayed a positive value from available experimental data. This compound is arguably more similar to the target compound. It was concluded that the prediction was acceptable as part of a weight of evidence.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available