Xylitol

Endpoint summary

Description of key information

QSAR WOE, OECD Toolbox and Times; not sensitizing. Reliability = 2

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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 adequate and reliable documentation / justification

Remarks:

The scientific validity of the (Q)SAR model has been established in accordance with the OECD Principles for (Q)SAR Model Validation.

Principles of method if other than guideline:

OECD Toolbox v3.1
Estimation by TIMES: Skin sensitization v. 16.19 with autoxidation
Toolbox prediction report is attached in IUCLID

GLP compliance:

no

Justification for non-LLNA method:

QSAR prediction

Remarks on result:

no indication of skin sensitisation

Remarks:

based on QSAR results

Results by QSAR utilising Times within the OECD Toolbox were negative indicating that the substance is not sensitising.

Interpretation of results:

GHS criteria not met

Conclusions:

Results by QSAR utilising Times within the OECD Toolbox were negative indicating that the substance is not sensitising.

Executive summary:

Results by QSAR utilising Times within the OECD Toolbox were negative indicating that the substance is not sensitising. The target substance falls within applicability domain of the prediction. Supporting documentation is provided in the attached prediction report.

 

Reference 2

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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 adequate and reliable documentation / justification

Remarks:

The scientific validity of the (Q)SAR model has been established in accordance with the OECD Principles for (Q)SAR Model Validation.

Principles of method if other than guideline:

OECD Toolbox v3.1
Toolbox prediction report is attached in IUCLID

GLP compliance:

no

Justification for non-LLNA method:

QSAR

Remarks on result:

no indication of skin sensitisation

Remarks:

based on QSAR results

EC3 results by QSAR utilising the OECD Toolbox were negative indicating that the substance is not sensitising.

Interpretation of results:

GHS criteria not met

Conclusions:

EC3 results by QSAR utilising the OECD Toolbox were negative indicating that the substance is not sensitising.

Executive summary:

EC3 results by QSAR utilising the OECD Toolbox were negative indicating that the substance is not sensitising. Supporting documentation is provided in the attached prediction report.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

There are a number of steps that a chemical is required to overcome in order for it to induce skin sensitisation. The steps include gaining access to the viable epidermis, protein binding, metabolic activation (if required), internalisation and processing by Langerhans cells (LC), transport of antigen by LC to draining lymph nodes, and presentation to and recognition by T lymphocytes. Of these steps, the rate determining one is the ability to bind with proteins to form a stable adduct. The binding is assumed to be covalent whereby the chemical behaves as an electrophile and the skin protein as a nucleophile. Efforts to predict skin sensitizers have thus focused on identifying the electrophilic features in chemicals and relating these back to skin sensitisation potential. Such mechanistic information has been encoded as protein binding alerts within the OECD Toolbox (Enoch et al, 2010). Alerting groups underpinned by 3D QSAR have been incorporated into expert systems such as TIMES-SS (Patlewicz et al, 2007). A qualitative read-across was attempted in the OECD Toolbox. Substances were categorised on the basis of common MOA - i.e. absence of alerting groups as flagged by the protein binding alert schemes. Data were taken from all protocols to maximise the number of analogues and thus the ability to investigate a read-across. The test substance was predicted to be non-sensitising. A prediction was also made using the TIMES-expert system. The test substance was found to be non-sensitising by TIMES.

 

Literature references

Enoch SJ, Ellison CM, Schultz TW, Cronin MTD. 2010. A review of the electrophilic reaction chemistry involved in covalent protein binding relevant to toxicity. Crit Rev Toxicol 41(9):783-802.

Patlewicz G, Dimitrov S, Low LK, Kern PS, Dimitrova GD, Comber MI, Aptula AO, Phillips RD, Niemelä J, Madsen C, Wedebye EB, Roberts DW, Bailey PT, Mekenyan OG. 2007. TIMES-SS - A promising tool for the assessment of skin sensitization hazard. A characterization with respect to the OECD validation principles for (Q)SARs and an external evaluation for predictivity. Reg. Toxicol. Pharmacol. 48(2): 225-239.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The test substance is neither structurally nor mechanistically (chemically) related to any known respiratory sensitizers and therefore is not expected to be a respiratory sensitizer.

Justification for classification or non-classification

The test substance is not expected to be a skin sensitizer based on QSAR evaluation. It is also not classified as a respiratory sensitizer due to a lack of any data for this endpoint, and any structural similarity with known respiratory sensitizers. Therefore, no classification is required for sensitisation according to EU Classification and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. (EC) No. 1272/2008.