Methyl 3-α,7-α-diacetoxy-12-α-hydroxy-5-β-cholan-24-oate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation

Remarks:

other: in silico prediction

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2013

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

QSAR approach: Different tools were used, when possible, in order to apply a consensus approach and thus enhance the reliability of the predictions. In fact, a single in silico prediction model may provide acceptable results. However, by definition all models are simulation of reality, and therefore they will never be completely accurate; sometimes a single model will not work. When multiple models and multiple approaches are combined in a single consensus score, more accurate predictions can be achieved.
If two prediction methods that use data and different approaches are consistent, the reliability of prediction is better. The errors of a model/approach should be different from another, and therefore compensate.

Several computational tools are nowadays available for applying in silico approaches. Among them, for QSAR predictions the following was selected and used for the endpoint:
Toxtree (Ideaconsultant, version 2.5.0) is a flexible and user-friendly open-source application that places chemicals into categories and predicts various kinds of toxic effect by applying decision tree approaches. The following decision trees are currently implemented: the Cramer classification scheme, Verhaar scheme for aquatic modes of action, rulebases for skin and eye irritation and corrosion, Benigni-Bossa rulebase for mutagenicity and carcinogenicity, structural alerts for identification of Michael Acceptors, START rulebase for persistance / biodegradation potential.
Vega Application (Virtual Models for evaluating the properties of chemicals within a global architecture) (VegaNIC application, Laboratory of Environmental Chemistry and Toxicology of Mario Negri Institute of Pharmacological Research, version 1.0.8) is a platform developed on the basis of contributions from the EU projects CAESAR, ORCHESTRA and ANTARES. It includes CAESAR QSAR model for mutagenicity based on a data set that includes 4225 compounds. It is an integrated model made of two complementary techniques: a machine learning algorithm (SVM), to build an early model with the best statistical accuracy, equipped with an expert facility for false negatives removal based on known structural alerts, to refine its predictions. Thus, the mutagenicity model could classify a compound as mutagen even if it is formally out of the applicability domain. This behaviour is normal for this model and it is related to the use of structural alerts. It also include the CAESAR skin sensitization model, which provides a qualitative prediction of skin sensitisation on mouse (local lymph node assay). The model consists in an Adaptive Fuzzy Partition (AFP) based on 8 descriptors. The AFP produces as output two values positive and negative that represent the belonging degree respectively to the sensitiser and non-sensitise classes. The applicability domain of predictions is assessed using an Applicability Domain Index (ADI) that has values from 0 (worst case) to 1 (best case). The ADI is calculated by grouping several other indices, each one taking into account a particular issue of the applicability domain..

GLP compliance:

no

Type of study:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Methyl 3-α,7-α-diacetoxy-12-α-hydroxy-5-β-cholan-24-oate

EC Number:

223-151-6

EC Name:

Methyl 3-α,7-α-diacetoxy-12-α-hydroxy-5-β-cholan-24-oate

Cas Number:

3749-87-9

Molecular formula:

C29H46O7

IUPAC Name:

methyl 3-α,7-α-diacetoxy-12-α-hydroxy-5-β-cholan-24-oate

Results and discussion

Any other information on results incl. tables

Name	Toxtree	Vega	Vega reliability	CONSENSUS Eye irritation
methyl 3-α,7-α-diacetoxy-12-α-hydroxy-5-β-cholan-24-oate	NO SKIN SENSITIZER	NO SKIN SENSITIZER	Low reliability	NO SKIN SENSITIZER

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

The methyl 3-α,7-α-diacetoxy-12-α-hydroxy-5-β-cholan-24-oate is NOT a SKIN SENSITIZER.