Some brominated flame retardants (BFRs), as PBDEs, are persistent, bioaccumulative, toxic (PBT) and are restricted/prohibited under various legislations. They are replaced by "safer" flame retardants (FRs), such as new BFRs or organophosphorous compounds. However, informations on the PBT behaviour of these substitutes are often lacking. The PBT assessment is required by the REACH regulation and the PBT chemicals should be subjected to authorization. Several new FRs, proposed and already used as safer alternatives to PBDEs, are here screened by the cumulative PBT Index model, implemented in QSARINS (QSAR-Insubria), new software for the development/validation of QSAR models. The results, obtained directly from the chemical structure for the three studied characteristics altogether, were compared with those from the US-EPA PBT Profiler: the two different approaches are in good agreement, supporting the utility of a consensus approach in these screenings. A priority list of the most harmful FRs, predicted in agreement by the two modelling tools, has been proposed, highlighting that some supposed "safer alternatives" are detected as intrinsically hazardous for their PBT properties. This study also shows that the PBT Index could be a valid tool to evaluate appropriate and safer substitutes, a priori from the chemical design, in a benign by design approach, avoiding unnecessary synthesis and tests. (C) 2015 Elsevier B.V. All rights reserved.