Comparison between bioconcentration factor (BCF) data provided by industry to the European Chemicals Agency (ECHA) and data derived from QSAR models.

The bioconcentration factor (BCF) is the ratio of the concentration of a chemical in an organism to the concentration in the surrounding environment at steady state. It is a valuable indicator of the bioaccumulation potential of a substance. BCF is an essential environmental property required for regulatory purposes within the Registration, Evaluation, Authorization and restriction of Chemicals (REACH) and Globally Harmonized System (GHS) regulations. In silico models for predicting BCF can facilitate the risk assessment for aquatic toxicology and reduce the cost and number of animals used. The aim of the present study was to examine the correlation of BCF data derived from the dossiers of registered chemicals submitted to the European Chemical Agency (ECHA) with the results of a battery of Quantitative Structure-Activity Relationship (QSAR). After data pruning, statistical analysis was performed using the predictions of the selected models. Results in terms of R(2) had low rating around 0.5 for the pruned dataset. The use of the model applicability domain index (ADI) led to an improvement of the performance for compounds falling within it. The variability of the experimental data and the use of different parameters to define the applicability domain can influence the performance of each model. All available information should be adapted to the requirements of the regulation to obtain a safe decision.

[1]  J. Arnot,et al.  Use of the bioaccumulation factor to screen chemicals for bioaccumulation potential , 2012, Environmental toxicology and chemistry.

[2]  J. Tarazona,et al.  Analysis of the ecotoxicity data submitted within the framework of the REACH Regulation. Part 2. Experimental aquatic toxicity assays. , 2014, The Science of the total environment.

[3]  M. Pavan,et al.  The role of the European Chemicals Bureau in promoting the regulatory use of (Q)SAR methods , 2007, SAR and QSAR in environmental research.

[4]  Roberto Todeschini,et al.  QSAR models for bioconcentration: is the increase in the complexity justified by more accurate predictions? , 2015, Chemosphere.

[5]  B. Matthews.  Comparison of the predicted and observed secondary structure of T4 phage lysozyme. , 1975, Biochimica et biophysica acta.

[6]  Jon A Arnot,et al.  A food web bioaccumulation model for organic chemicals in aquatic ecosystems , 2004, Environmental toxicology and chemistry.

[7]  Emilio Benfenati,et al.  Evaluation and comparison of benchmark QSAR models to predict a relevant REACH endpoint: The bioconcentration factor (BCF). , 2015, Environmental research.

[8]  J. Madden,et al.  Development of a list of reference chemicals for evaluating alternative methods to in vivo fish bioaccumulation tests , 2014, Environmental toxicology and chemistry.

[9]  R. Saracci,et al.  Describing the validity of carcinogen screening tests. , 1979, British Journal of Cancer.

[10]  Emilio Benfenati,et al.  A new hybrid system of QSAR models for predicting bioconcentration factors (BCF). , 2008, Chemosphere.

[11]  Frank A. P. C. Gobas,et al.  A review of bioconcentration factor (BCF) and bioaccumulation factor (BAF) assessments for organic chemicals in aquatic organisms , 2006 .

[12]  Jia He,et al.  Investigation on the relationship between bioconcentration factor and distribution coefficient based on class-based compounds: The factors that affect bioconcentration. , 2014, Environmental toxicology and pharmacology.

[13]  Robert S. Boethling,et al.  Improved method for estimating bioconcentration/bioaccumulation factor from octanol/water partition coefficient , 1999 .

[14]  Judith C. Madden,et al.  Methods for assigning confidence to toxicity data with multiple values--Identifying experimental outliers. , 2014, The Science of the total environment.

[15]  Emilio Benfenati,et al.  Assessment and validation of the CAESAR predictive model for bioconcentration factor (BCF) in fish , 2010, Chemistry Central journal.

[16]  Manuela Pavan,et al.  Review of Literature‐Based Quantitative Structure–Activity Relationship Models for Bioconcentration , 2008 .

[17]  Emilio Benfenati,et al.  A generalizable definition of chemical similarity for read-across , 2014, Journal of Cheminformatics.

[18]  J. Hermens,et al.  Classifying environmental pollutants , 1992 .

[19]  U. Tillmann,et al.  A systematic approach for evaluating the quality of experimental toxicological and ecotoxicological data. , 1997, Regulatory toxicology and pharmacology : RTP.

[20]  J. Tarazona,et al.  Analysis of the ecotoxicity data submitted within the framework of the REACH Regulation. Part 1. General overview and data availability for the first registration deadline. , 2014, The Science of the total environment.

[21]  Emilio Benfenati,et al.  Evaluation of QSAR Models for the Prediction of Ames Genotoxicity: A Retrospective Exercise on the Chemical Substances Registered Under the EU REACH Regulation , 2014, Journal of environmental science and health. Part C, Environmental carcinogenesis & ecotoxicology reviews.

[22]  Frank A. P. C. Gobas,et al.  A Generic QSAR for Assessing the Bioaccumulation Potential of Organic Chemicals in Aquatic Food Webs , 2003 .

[23]  Rajni Garg,et al.  Predicting the bioconcentration factor of highly hydrophobic organic chemicals. , 2014, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[24]  Horst Spielmann,et al.  A Critical Evaluation of the 2011 ECHA Reports on Compliance with the REACH and CLP Regulations and on the Use of Alternatives to Testing on Animals for Compliance with the REACH Regulation , 2011, Alternatives to laboratory animals : ATLA.