In Silico Model for Developmental Toxicity: How to Use QSAR Models and Interpret Their Results.
Modeling developmental toxicity has been a challenge for (Q)SAR model developers due to the complexity of the endpoint. Recently, some new in silico methods have been developed introducing the possibility to evaluate the integration of existing methods by taking advantage of various modeling perspectives. It is important that the model user is aware of the underlying basis of the different models in general, as well as the considerations and assumptions relative to the specific predictions that are obtained from these different models for the same chemical. The evaluation on the predictions needs to be done on a case-by-case basis, checking the analogs (possibly using structural, physicochemical, and toxicological information); for this purpose, the assessment of the applicability domain of the models provides further confidence in the model prediction. In this chapter, we present some examples illustrating an approach to combine human-based rules and statistical methods to support the prediction of developmental toxicity; we also discuss assumptions and uncertainties of the methodology.
Laboratory of Environmental Chemistry and Toxicology, Department of Environmental Health Sciences, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy. marco.marzo@marionegri.it.
Marco
M
Marzo
Laboratory of Environmental Chemistry and Toxicology, Department of Environmental Health Sciences, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
Alessandra
A
Roncaglioni
Existing Substances Risk Assessment Bureau, Health Canada, Ottawa, ON, Canada.
Sunil
S
Kulkarni
Existing Substances Risk Assessment Bureau, Health Canada, Ottawa, ON, Canada.
Tara S
TS
Barton-Maclaren
Mario Negri Institute for Pharmacological Research, IRCCS, Milan, Italy.
Emilio
E
Benfenati
D000818:Animals; D003198:Computer Simulation; D062313:Databases, Pharmaceutical; D006801:Humans; D008954:Models, Biological; D019055:No-Observed-Adverse-Effect Level; D021281:Quantitative Structure-Activity Relationship; D018675:Toxicity Tests / Q000379:methods*
Developmental toxicity; OECD; Predictive reliability; QSAR; Similarity