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

Endpoint summary

Description of key information

Methyl 3-α,7-α-diacetoxy-12-oxo-5-β-cholan-24-oate resulted not irritating to the skin and the eyes. 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation / corrosion

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

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:
ACD/Percepta (Advanced Chemistry Development, Inc., Pharma Algorithms, Inc.) (release 2012) is a suite of comprehensive tools for the prediction of basic toxicity endpoints, including hERG Inhibition, CYP3A4 Inhibition, Genotoxicity, Acute Toxicity, Aquatic Toxicity, Eye/Skin Irritation, Endocrine System Disruption, and Health Effects. Predictions are made from chemical structure and based upon large validated databases and QSAR models, in combination with expert knowledge of organic chemistry and toxicology. It also allows to evaluate the robustness of the prediction by examining compounds similar to the target from the training set, together with literature data and reference. The models also provide an estimation of the reliability of the prediction, by a reliability index (RI). This index provides values in a range from 0 to 1 and gives an evaluation of whether a submitted compound falls within the Model Applicability Domain. Estimation of the RI takes into account the following two aspects: similarity of the tested compound to the training set and the consistency of experimental values for similar compounds. If the RI is less than 0.3 the prediction has to be considered not reliable while if RI is more than 0.5 the prediction results are considered reliable.
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.

GLP compliance:

no

Name	ACD/Percepta Positive probability	ACD/Percepta Prediction call	Toxtree Skin irritation	CONSENSUS Skin irritation
Methyl 3-α,7-α-diacetoxy-12-oxo-5-β-cholan-24-oate	0.23	NOT IRRITANT	NOT IRRITANT	NOT IRRITANT

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

the two predictors were in agreement leading to the consensus predictions of NOT SKIN IRRITATION potential for methyl 3-α,7-α-diacetoxy-12-oxo-5-β-cholan-24-oate.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation

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

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.
ACD/Percepta (Advanced Chemistry Development, Inc., Pharma Algorithms, Inc.) (release 2012) is a suite of comprehensive tools for the prediction of basic toxicity endpoints, including hERG Inhibition, CYP3A4 Inhibition, Genotoxicity, Acute Toxicity, Aquatic Toxicity, Eye/Skin Irritation, Endocrine System Disruption, and Health Effects. Predictions are made from chemical structure and based upon large validated databases and QSAR models, in combination with expert knowledge of organic chemistry and toxicology. It also allows to evaluate the robustness of the prediction by examining compounds similar to the target from the training set, together with literature data and reference. The models also provide an estimation of the reliability of the prediction, by a reliability index (RI). This index provides values in a range from 0 to 1 and gives an evaluation of whether a submitted compound falls within the Model Applicability Domain. Estimation of the RI takes into account the following two aspects: similarity of the tested compound to the training set and the consistency of experimental values for similar compounds. If the RI is less than 0.3 the prediction has to be considered not reliable while if RI is more than 0.5 the prediction results are considered reliable.

GLP compliance:

no

Species:

rabbit

Name	ACD/Percepta Positive probability	ACD/Percepta Prediction call	Toxtree Eye irritation	CONSENSUS Eye irritation
Methyl 3-α,7-α-diacetoxy-12-oxo-5-β-cholan-24-oate	0.10	NOT IRRITANT	NOT IRRITANT	NOT IRRITANT

Interpretation of results:

not irritating

Remarks:

Migrated information

Conclusions:

The methyl 3-α,7-α-diacetoxy-12-oxo-5-β-cholan-24-oate is NOT EYE IRRITATION potential.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No experimental results with laboratory animals are available, but the in silico study is well documented and results are calculated according to validated prediction tools.

Regarding skin irritation, tools predicted that methyl 3-α,7-α-diacetoxy-12-oxo-5-β-cholan-24-oate is negative.

Regarding eye irritation, tools predicted methyl 3-α,7-α-diacetoxy-12-oxo-5-β-cholan-24-oate negative.

Justification for selection of skin irritation / corrosion endpoint:
No experimental results with laboratory animals are available, but the in silico study is well documented and results are calculated according to validated prediction tools.

Justification for selection of eye irritation endpoint:
No experimental results with laboratory animals are available, but the in silico study is well documented and results are calculated according to validated prediction tools.

Justification for classification or non-classification

According to the results of the QSAR predictions methyl 3-α,7-α-diacetoxy-12-oxo-5-β-cholan-24-oate is classified neither for skin irritation corrosion nor for eye irritation according to Regulation 1272/2008/EC.