Allyl alcohol

Endpoint summary

Description of key information

For the endpoint skin sensitization three different, scientifically valid QSAR models were applied within a weight-of-evidence approach.

Profiling (OECD QSAR Toolbox)

As a first step, profiling with the OECD QSAR Toolbox (version 4.0) was performed. Since protein-binding is a crucial step for a molecule to elicit skin sensitisation as described in the ‘Adverse Outcome Pathway for skin sensitisation’ (OECD, 2014), profilers detecting structural alerts for protein-binding have been analysed. This allows an initial assessment of skin sensitising potential. Six profilers for protein-binding (one endpoint-specific profiler and five general profilers) were analysed. No structural alert associated with protein-binding was detected by any of the six profilers. This provides evidence that no skin sensitising potential can be expected for Allyl alcohol.

Read-across (OECD QSAR Toolbox)

Read-across on Allyl alcohol was performed with the OECD QSAR Toolbox (version 4.0). In this read-across Allyl alcohol was predicted negative. The descriptor used in this category approach is the partition coefficient log KoW. The target chemical Allyl alcohol has a calculated log KoW value of 0.21 (calculated by Epiwin, which is implemented in the Toolbox). With this value the target substance builds the lower limit of the category. Therefore, it is classified to lie outside of the applicability domain of this model. The estimation of a value for a member of a category that is near or at the category boundary using measured values from internal category members is defined as "extrapolation" in the ‘ECHA Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals, 2008’. Although interpolation between category members is preferred to extrapolation, extrapolation is also advised as a possible approach to fill data-gaps in a read-across (ECHA Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals, 2008). Therefore, this prediction is accepted within the frame of a weight-of-evidence approach. It provides evidence that Allyl alcohol is not sensitizing. This prediction is in concordance with a negative sensitisation result derived from an experimental GMPT study (OECD 406) conducted with the registered substance Allyl alcohol (prop-2 -en-1 -ol, CAS 107 -18 -6), as provided by the OECD QSAR Toolbox.

QSAR (CAESAR 2.1.6 provided by VEGA)

To provide further evidence, skin sensitisation of Allyl alcohol was predicted with the Skin Sensitization model CAESAR 2.1.6, which is implemented in the QSAR tool VEGA (version 1.1.4.). Allyl alcohol is predicted to be "non sensitiser". This prediction is reliable and lies within the applicability domain of the model. This gives strong evidence that Allyl alcohol is not sensitising.

QSAR (MultiCASE CASE Ultra commercial model A33)

Finally the Skin Sensitization model CASE Ultra was used to predict the skin sensitisation of Allyl alcohol. Allyl alcohol is predicted to be "non sensitiser". This prediction is reliable and lies within the applicability domain of the model. This gives strong evidence that Allyl alcohol is not sensitising.

Conclusion

The predictions of the applied silico methods are consistent, reliable and are in line with a mechanistic understanding of the Adverse Outcome Pathway of skin sensitisation. As a conclusion, Allyl alcohol is not sensitising. These predictions are also in line with a negative sensitisation result derived from an experimental GMPT study (OECD 406) conducted with the registered substance Allyl alcohol, as provided by the OECD QSAR Toolbox.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation, other

Remarks:

QSAR prediction for skin sensitisation (CAESAR)

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

2017-09-05

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 adequate and reliable documentation / justification

Justification for type of information:

Please refer to the OPRF and QMRF report attached in section Attached Justification.

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

Skin sensitisation of Allyl alcohol was predicted with CAESAR model implemented in the VEGA tool.

Parameter:

other: QSAR

Remarks on result:

no indication of skin sensitisation

Remarks:

Allyl alcohol is predicted 'negative'.

Allyl alcohol is predicted to be a non-sensitiser by the skin sensitization model CAESAR.

Conclusions:

Allyl alcohol is not sensitising.

Executive summary:

Skin sensitisation of Allyl alcohol was predicted with the Skin Sensitization model CAESAR 2.1.6, which is implemented in the QSAR tool VEGA (version 1.1.4.). Allyl alcohol is predicted to be "non sensitiser". This prediction is reliable, it is generated by a scientifically valid model and lies within the applicability domain (please refer also to the QPRF and QMRF attached in the section 'Attached Justification').

Reference 2

Endpoint:

skin sensitisation, other

Remarks:

QSAR: read-across performed with the OECD QSAR Toolbox

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

2017-09-05

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE
OECD QSAR Toolbox

2. MODEL (incl. version number)
version 4.0

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CAS: 107-18-6

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Please refer to the attached QPRF report

5. APPLICABILITY DOMAIN
Please refer to the attached QPRF report

6. ADEQUACY OF THE RESULT
Please refer to the attached QPRF report

Guideline:

other: REACH Guidance on QSARs R.6

Version / remarks:

Read-across was performed with the QSAR Toolbox 4.0

Parameter:

other: QSAR

Remarks on result:

no indication of skin sensitisation

Remarks:

Allyl alcohol is predicted 'negative'

Conclusions:

There is great evidence that Allyl alcohol is not sensitising.

Executive summary:

Read-across on Allyl alcohol was performed with the OECD QSAR Toolbox (version 4.0). In this read-across Allyl alcohol is predicted negative (please refer to the attached QPRF in Section Attached Justification). The descriptor used in this category approach is the partition coefficient log KoW. The target chemical Allyl alcohol has a calculated log KoW value of 0.21. With this value it builds the lower limit of the category. Therefore, it is classified to lie outside of the applicability domain of this model. The estimation of a value for a member of a category that is near or at the category boundary using measured values from internal category members is defined as "extrapolation" in the "ECHA Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals". Although interpolation is preferred to extrapolation between category members, extrapolation is also a possible approach to fill data-gaps in a read-across (ECHA Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals). Therefore, this prediction is accepted within the frame of a weight of evidence approach. It provides strong evidence that Allyl alcohol is not sensitizing. Importantly, this prediction is in concordance with a negative sensitisation result derived from an experimental GMPT study conducted with the registered substance Allyl alcohol (prop-2 -en-1 -ol, CAS 107 -18 -6), as provided by the OECD QSAR Toolbox.

Reference 3

Endpoint:

skin sensitisation, other

Remarks:

SAR-Profiling of structural alerts for skin sensitisation (OECD QSAR Toolbox)

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

2017-09-05

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Justification for type of information:

1. SOFTWARE
OECD QSAR Toolbox

2. MODEL (incl. version number)
version 4.0

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CAS: 107-18-6

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Name of profilers:
Protein binding alerts for skin sensitization by OASIS v1.4
Protein binding alerts by OASIS v1.4
Protein binding alerts by OECD
Protein binding potency Cys (DPRA 13%)
Protein binding potency Lys (DPRA 13%)
Protein binding potency

5. APPLICABILITY DOMAIN
The aim of these profilere is to investigate the presence of alerts within the target molecules responsible for interaction or covalent bindings with proteins. For detailed information, please refer to the attached reports about the specific profilers.

6. ADEQUACY OF THE RESULT
These profiling results are used in a weight-of-evidenc approach to assess the skin sensitising potential of allyl alcohol. The selected profilers detect structural alerts, which are associated with the potential to bind to or interact with proteins. The binding to skin proteins is the first step of the Adverse Outcome Pathway for skin sensitisation. Binding to skin proteins is essentiel to induce a specific memory T-cell response associated with skin sensitisation.

Guideline:

other: REACH Guidance on QSARs R.6

Version / remarks:

Profiling was performed with the QSAR Toolbox Version 4.0

Parameter:

other: Profiling

Remarks on result:

no indication of skin sensitisation

No structural alert for protein-binding was detected by any of the six relevant profilers.

Conclusions:

The profiling results of Allyl alcohol in the OECD QSAR Toolbox revealed that no structural alert associated with binding to proteins was detected. Binding of skin proteins is the first essentiel step to elicit skin sensitisation. Therefore, the fact that six different profilers do not detect any structural alert associated with protein-binding, provides evidence that no skin sensitising potential can be expected for Allyl alcohol.

Executive summary:

Allyl alcohol has been profiled with the OECD QSAR Toolbox, version 4.0. The relevant profilers associated with the Adverse Outcome Pathway of skin sensitisation are evaluated. The profiling results of Allyl alcohol in the OECD QSAR Toolbox revealed that no structural alert associated with binding to proteins was detected. Binding of skin proteins is the first essentiel step to elicit skin sensitisation. Therefore, the fact that six different profilers do not detect any structural alert associated with protein-binding, provides evidence that no skin sensitising potential can be expected for Allyl alcohol.

Reference 4

Endpoint:

skin sensitisation, other

Remarks:

QSAR prediction for skin sensitisation (CASE Ultra)

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

2017-09-05

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 adequate and reliable documentation / justification

Justification for type of information:

Please refer to the OPRF and QMRF report attached in section 'Attached Justification'.

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

A prediction was performed with the QSAR model CASE Ultra.

Parameter:

other: QSAR

Remarks on result:

no indication of skin sensitisation

Remarks:

Allyl alcohol is predicted 'negative'

Allyl alcohol is predicted to be a non-sensitiser by the skin sensitization model CASE Ultra.

Conclusions:

Allyl alcohol is not sensitising.

Executive summary:

Skin sensitisation of Allyl alcohol was predicted with the Skin Sensitization model CASE Ultra, which is implemented in the 'Danish QSAR Database'. Allyl alcohol is predicted to be "non sensitiser". This prediction is reliable, it was generated by a scientifically valid model and lies within the applicability domain (please refer also to the QPRF and QMRF attached in the section 'Attached Justification').

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Allyl alcohol is not classified as a skin sensitiser according to Regulation (EC) No 1272/2008, because there is no evidence for a skin sensitising mode of action. This is underlined by three scientifically valid QSAR models making the consistent prediction that Allyl alcohol is not sensitising.