title: An alternative QSAR-based approach for predicting the bioconcentration factor for regulatory purposes.
abstract: The REACH (Registration, Evaluation, Authorization and restriction of Chemicals) and BPR (Biocide Product Regulation) regulations strongly promote the use of non-animal testing techniques to evaluate chemical risk. This has renewed the interest towards alternative methods such as QSAR in the regulatory context. The assessment of Bioconcentration Factor (BCF) required by these regulations is expensive, in terms of costs, time, and laboratory animal sacrifices. Herein, we present QSAR models based on the ANTARES dataset, which is a large collection of known and verified experimental BCF data. Among the models developed, the best results were obtained from a nine-descriptor highly predictive model. This model was derived from a training set of 608 chemicals and challenged against a validation and blind set containing 152 and 76 chemicals. The model's robustness was further controlled through several validation strategies and the implementation of a multi-step approach for the applicability domain. Suitable safety margins were used to increase sensitivity. The easy interpretability of the model is ensured by the use of meaningful biokinetics descriptors. The satisfactory predictive power for external compounds suggests that the new models could represent a reliable alternative to the in vivo assay, helping the registrants to fulfill regulatory requirements in compliance with the ethical and economic necessity to reduce animal testing.
authors.affiliation: Dipartimento di Farmacia - Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Bari, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gissi
authors.forename: Domenico
authors.initials: D
authors.lastname: Gadaleta
authors.forename: Matteo
authors.initials: M
authors.lastname: Floris
authors.forename: Stefania
authors.initials: S
authors.lastname: Olla
authors.forename: Angelo
authors.initials: A
authors.lastname: Carotti
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Emilio
authors.initials: E
authors.lastname: Benfenati
authors.forename: Orazio
authors.initials: O
authors.lastname: Nicolotti
mesh_terms: D000465:Algorithms; D000826:Animal Testing Alternatives / Q000379:methods* / Q000592:standards; D015386:Hazardous Substances / Q000737:chemistry / Q000633:toxicity*; D008954:Models, Biological; D011237:Predictive Value of Tests; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results; D018675:Toxicity Tests / Q000379:methods* / Q000592:standards
chemical_list: D015386:Hazardous Substances