title: A new integrated in silico strategy for the assessment and prioritization of persistence of chemicals under REACH.
abstract: The fact that chemicals can be recalcitrant and persist in the environment arouses concern since their effects may seriously harm human and environmental health.We compiled three datasets containing half-life (HL) data on sediment, soil and water compartments in order to build in silico models and, finally, an integrated strategy for predicting persistence to be used within the EU legislation Registration, Evaluation, Authorisation and restriction of CHemicals (REACH). After splitting the datasets into training (80%) and test sets (20%), we developed models for each compartment using the k-nearest neighbor algorithm (k-NN). Accuracy was higher than 0.79 and 0.76 respectively in the training and test sets for all three compartments. To support the k-NN predictions, we identified some structural alerts, using SARpy software, with a high-true positive percentage in the test set and some chemical classes related to persistence using the software IstChemFeat. All these results were combined to build an integratedmodel and to reach to an overall conclusion (based on assessment and reliability) on the persistenceof the substance. The results on the external validation set were very encouraging and support the idea that this tool can be used successfully for regulatory purposes and to prioritize substances.
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Department of Environmental Health Sciences, Laboratory of Environmental Chemistry and Toxicology, Via La Masa, 19, 20159 Milan, Italy. Electronic address: fabiola.pizzo@marionegri.it.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Pizzo
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Department of Environmental Health Sciences, Laboratory of Environmental Chemistry and Toxicology, Via La Masa, 19, 20159 Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Lombardo
authors.affiliation: Umweltbundesamt (UBA) - German Federal Environment Agency, Wörlitzer Platz 1, 06844 Dessau-Roßlau, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Brandt
authors.affiliation: Kode s.r.l., Via Nino Pisano, 14, 56122 Pisa, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Manganaro
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Department of Environmental Health Sciences, Laboratory of Environmental Chemistry and Toxicology, Via La Masa, 19, 20159 Milan, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Benfenati
mesh_terms: D000465:Algorithms; D000818:Animals; D016000:Cluster Analysis; D003198:Computer Simulation; D004784:Environmental Monitoring / Q000379:methods*; D058735:Environmental Policy / Q000331:legislation & jurisprudence; D004785:Environmental Pollutants / Q000032:analysis*; D005062:European Union
chemical_list: D004785:Environmental Pollutants
keywords: Chemical classes; In silico; PBT; Persistence; Structural alerts; k-NN