Assessment and validation of the CAESAR predictive model for bioconcentration factor (BCF) in fish

Abstract

BackgroundBioconcentration factor (BCF) describes the behaviour of a chemical in terms of its likelihood of concentrating in organisms in the environment. It is a fundamental property in recent regulations, such as the European Community Regulation on chemicals and their safe use or the Globally Harmonized System for classification, labelling and packaging. These new regulations consider the possibility of reducing or waiving animal tests using alternative methods, such as in silico methods. This study assessed and validated the CAESAR predictive model for BCF in fish.ResultsTo validate the model, new experimental data were collected and used to create an external set, as a second validation set (a first validation exercise had been done just after model development). The performance of the model was compared with BCFBAF v3.00. For continuous values and for classification purposes the CAESAR BCF model gave better results than BCFBAF v3.00 for the chemicals in the applicability domain of the model. R2 and Q2 were good and accuracy in classification higher than 90%. Applying an offset of 0.5 to the compounds predicted with BCF close to the thresholds, the number of false negatives (the most dangerous errors) dropped considerably (less than 0.6% of chemicals).ConclusionsThe CAESAR model for BCF is useful for regulatory purposes because it is robust, reliable and predictive. It is also fully transparent and documented and has a well-defined applicability domain, as required by REACH. The model is freely available on the CAESAR web site and easy to use. The reliability of the model reporting the six most similar compounds found in the CAESAR dataset, and their experimental and predicted values, can be evaluated.

Developmental toxicity screening in zebrafish

“…Thus, studies that investigate bioaccumulation and metabolism of chemicals in zebrafish are needed. Based on the structure of the chemical, it will likely be possible to measure water solubility, uptake, and accumulation of a select number of chemicals to predict that of other chemicals with similar structures using quantitative structure-activity relationships (Lombardo et al, 2010;Piir et al, 2010). Today, there are computer programs available to do in silico metabolism in mammals (reviewed in Kulkarni et al, 2005).…”

Residual-QSAR. Implications for genotoxic carcinogenesis

“…This strategy is particularly useful in the first phases of validation for a new compound, before entering the industrial mainstream. This process primarily consists of preliminary screening based on models of literature and their extrapolations (Phase I), followed by the read-across, grouping and construction of new models employing the available commercial or non-commercial models, such as OncoLogic [15], HazardExpert [16], Derek [17], ToxTree [18], Multicase [19], and CAESAR [20,21] (Phase II), and eventually concluding with in vitro or in vivo assays (Phase III).…”

Assessment of PBTs in the European Union: a critical assessment of the proposed evaluation scheme with reference to plant protection products

“…Therefore, false positives are highly probable and K OW must be assumed only as an indicator of worst-case conditions of the 'potential' for bioconcentration. More complex models, based on several molecular properties and descriptors, have been recently developed [83][84][85]. These models are more powerful than the simple relationship with K OW ; however, with the exception of EPISUITE 4.1 [83], they are limited to prediction of bioconcentration and do not consider biotransformation and/ or excretion.…”