Hexane-1,2,6-triol

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Remarks:

in silico toxicity prediction by DEREK Nexus

Type of information:

(Q)SAR

Adequacy of study:

supporting study

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
Nexus: 2.1.1
DEREK Nexus: 5.0.2

2. MODEL (incl. version number)
Derek Nexus v5.0 contains 80 alerts for skin sensitisation, together with reasoning rules encoding physicochemical descriptors.

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
Smiles: OCCCCC(O)CO

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]
- Defined endpoint:
DEREK Nexus is used for the prediction of the outcome of in vivo skin sensitization testing as required in REACH Annex VII, 8.3.2. The model is able to predict the outcome of skin sensitization testing in animals (for more details see the attached QMRF).

- Unambiguous algorithm:
DEREK Nexus is a structure-based toxicity prediction tool that uses a knowledge base to match parts of the query structure (toxicophores) to alerts in the knowledge base and applies reasoning to assess the likelihood for a prediction. Reasoning considers evidence outlined in a set of rules to provide a logical outcome (for more details see the attached QMRF).

5. APPLICABILITY DOMAIN
[Explain how the substance falls within the applicability domain of the model]
The scopes of the structure-activity relationships describing the skin sensitization endpoint are defined by the developer to be the applicability domain for the model (for more details see the attached QMRF).

6. ADEQUACY OF THE RESULT
[Explain how the prediction fits the purpose of classification and labelling and/or risk assessment]
During the analysis, the test item did not activate an alert or reasoning rule in Derek and a "nothing-to-report" result is generated. For the endpoint of skin sensitisation, which features multiple alerts believed to cover most of the mechanisms and chemical classes responsible for activity, ‘nothing to report’ may be extrapolated to a negative prediction (for more details see the attached QMRF). Thus, the prediction gives a strong hint for the absence of skin sensitizing properties of the test item, but as a stand-alone result it is not considered adequate to fulfill the information requirement described in Annex VII section 8.3.2. Thus, further information from complementing prediction tools on the endpoint skin sensitization for an Annex VII registration is required.

Data source

Reference

Title:

DEREK Nexus v.5.0.2

Year:

2016

Bibliographic source:

Lhasa Limited

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

- Software tool(s) used including version:
Nexus: 2.1.1, DEREK Nexus: 5.0.2

- Model(s) used:
Derek Nexus v5.0 contains 80 alerts for skin sensitisation, together with reasoning rules encoding physicochemical descriptors.

- Model description: see field 'Justification for non-standard information'

- Justification of QSAR prediction: see field 'Justification for type of information'

-References:
Judson et al. (2013) ‘Assessing Confidence in Predictions made by Knowledge-Based Systems’, Toxicology Research, vol. 2, no. 1, pp. 70-79. http://pubs.rsc.org/en/content/articlelanding/2013/tx/c2tx20037f
Greene N, Judson P, Langowski J, Marchant CA (1999). Knowledge based expert systems for toxicity and metabolism prediction: DEREK, StAR and METEOR. SAR & QSAR in Environmental Research 10, 299-313.
Sanderson DM & Earnshaw CG (1991). Computer prediction of possible toxic action from chemical structure; The DEREK system. Human and Experimental Toxicology 10, 261-273.

GLP compliance:

no

Test material

Test material information

Constituent 1

Specific details on test material used for the study:

Smiles: OCCCCC(O)CO

Results and discussion

In vivo (LLNA)

Results

Parameter:

EC3

Test group / Remarks:

Tthe test item did not activate an alert or reasoning rule in Derek.

Remarks on result:

no indication of skin sensitisation based on QSAR/QSPR prediction

Any other information on results incl. tables

During the analysis, the test item did not activate an alert or reasoning rule in Derek and a "nothing-to-report" result is generated. For the endpoint of skin sensitisation, which features multiple alerts believed to cover most of the mechanisms and chemical classes responsible for activity, ‘nothing to report’ may be extrapolated to a negative prediction. Thus, the prediction gives a strong hint for the absence of skin sensitizing properties of the test item, but as a stand-alone result it is not considered adequate to fulfill the information requirement for skin sensitization.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification