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

Endpoint summary

Description of key information

The predicted oral LD50 in rats is 1600 mg/kg bw. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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.

GLP compliance:

no

Test type:

other: in silico prediction

Species:

rat

Sex:

not specified

Dose descriptor:

LD50

Effect level:

1 600 mg/kg bw

Remarks on result:

other: Reliability index: 0.57

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 prediction of test itme is 1600 mg7kg.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 600 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

exposure considerations

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A predicted oral LD₅₀in rats value is available (LD₅₀: 1600 mg/kg bw). No values are available for inhalation and dermal routes, and no experimental values have been produced, because not necessary, considering that exposure by these routes is not significant and unlikely. A subcutaneous LD₅₀in rabbits is available in literature for the similar substance ursodeoxycholic acid and according to this value (LD₅₀: > 2000 mg/kg bw) it can be supposed that acute dermal toxicity will be low.

Justification for selection of acute toxicity – inhalation endpoint
No experimental data was deemed necessary for inhalation route, because the substance is for professional use only and, at the workplace, suitable respiratory personal protective equipment are adopted in order to avoid workers exposure. Therefore no exposure is expected by inhalation route.

Justification for selection of acute toxicity – dermal endpoint
No experimental data was deemed necessary for dermal route, because the substance is for professional use only and, at the workplace, suitable personal protective equipment are adopted in order to avoid workers exposure. Moreover, no dermal toxicity is expected on the basis of the available data on subcutaneous acute toxicity in rabbits (LD50 > 2000 mg/kg bw), basing on a read-across approach.

Justification for classification or non-classification

In conclusion, basing on the available toxicological information, no classification for acute toxicity by inhalation and dermal routes is deemed necessary for methyl 3-α,7-α-diacetoxy-12-oxo-5-β-cholan-24-oate, according to Regulation 1272/2008/EU. Methyl 3-α,7-α-diacetoxy-12-oxo-5-β-cholan-24-oate is instead classified for acute toxicity by oral route as Acute Tox. 2, H302.