QSPR as a support for the EU REACH regulation and rational design of environmentally safer chemicals: PBT identification from molecular structureElectronic supplementary information (ESI) available: Table S1 reports the list of the 250 chemicals investigated, the experimental and predicted values of the studied endpoints, the values of the molecular descriptors selected for the proposed QSAR Model, information on the structural Applicability Domain, and the results of the PBT screening by U.S EP

• Main Authors: Papa, Ester, Gramatica, Paola
• Format: Journal Article
• Language: English
• Published: 11.05.2010
• ISSN: 1463-9262; 1463-9270
• DOI: 10.1039/b923843c

The chemicals that are jointly Persistent, Bioaccumulative and Toxic (PBT) are substances of very high concern (SVHC) and subject to an authorization step in the new European REACH regulation, which includes plans for safer substitutions of recognized hazardous compounds. The limited availability of experimental data necessary for the hazard/risk assessment of chemicals and the expected high costs have increased the interest, also in REACH, for alternative predictive in silico methods, such as Quantitative Structure-Activity (Property) Relationships (QSA(P)Rs). A structurally-based approach is proposed here for a holistic screening of potential PBTs in the environment. Persistence, bioconcentration and toxicity data available for a set of 180 organic chemicals, some of which are known PBTs, have been combined in a multivariate approach by Principal Component Analysis. This method is applied to rank the studied compounds according to their cumulative PBT behaviour; this ranking can be defined as a PBT Index. A simple, robust and externally predictive QSPR multiple linear regression model (MLR), which is based on four molecular descriptors, has been developed for the PBT Index. This QSPR model is proposed as a hazard screening tool, applicable also by regulators, for the early identification and prioritization of not yet known PBTs, only on the basis of the knowledge of their molecular structure. New, safer chemicals can be designed as alternatives to hazardous PBT chemicals by applying the proposed QSPR model, according to the green chemistry philosophy of "benign by design". A consensus approach is also proposed from the comparison of the results obtained by different screening methods. A QSAR model was developed to predict the potential PBT behaviour of existing and not yet synthesised organic compounds; this model is particularly useful for the identification of unsafe chemicals and of possible alternatives only on the basis of their chemical structures.