Integration of QSAR models for bioconcentration suitable for REACH

Andrea Gissi, Orazio Nicolotti, Angelo Carotti, Domenico Gadaleta, Anna Lombardo, Emilio Benfenati

Research output: Contribution to journalArticlepeer-review

Abstract

QSAR (Quantitative Structure Activity Relationship) models can be a valuable alternative method to replace or reduce animal test required by REACH. In particular, some endpoints such as bioconcentration factor (BCF) are easier to predict and many useful models have been already developed. In this paper we describe how to integrate two popular BCF models to obtain more reliable predictions. In particular, the herein presented integrated model relies on the predictions of two among the most used BCF models (CAESAR and Meylan), together with the Applicability Domain Index (ADI) provided by the software VEGA. Using a set of simple rules, the integrated model selects the most reliable and conservative predictions and discards possible outliers. In this way, for the prediction of the 851 compounds included in the ANTARES BCF dataset, the integrated model discloses a R2 (coefficient of determination) of 0.80, a RMSE (Root Mean Square Error) of 0.61log units and a sensitivity of 76%, with a considerable improvement in respect to the CAESAR (R2=0.63; RMSE=0.84log units; sensitivity 55%) and Meylan (R2=0.66; RMSE=0.77log units; sensitivity 65%) without discarding too many predictions (118 out of 851). Importantly, considering solely the compounds within the new integrated ADI, the R2 increased to 0.92, and the sensitivity to 85%, with a RMSE of 0.44log units. Finally, the use of properly set safety thresholds applied for monitoring the so called suspicious compounds, which are those chemicals predicted in proximity of the border normally accepted to discern non-bioaccumulative from bioaccumulative substances, permitted to obtain an integrated model with sensitivity equal to 100%.

Original languageEnglish
Pages (from-to)325-332
Number of pages8
JournalScience of the Total Environment
Volume456-457
DOIs
Publication statusPublished - Jul 1 2013

Keywords

  • Applicability domain
  • Bioconcentration factor
  • QSAR
  • REACH

ASJC Scopus subject areas

  • Environmental Chemistry
  • Pollution
  • Waste Management and Disposal
  • Environmental Engineering

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