| Title: | PBT assessment under REACH: Screening for low aquatic bioaccumulation with QSAR classifications based on physicochemical properties to replace BCF in vivo testing on fish |
| Author(s): | Nendza M; Kuhne R; Lombardo A; Strempel S; Schuurmann G; |
| Address: | "Analytical Laboratory AL-Luhnstedt, Bahnhofstrasse 1, 24816 Luhnstedt, Germany. Electronic address: nendza@al-luhnstedt.de. UFZ Department of Ecological Chemistry, Helmholtz Centre for Environmental Research, Permoserstr. 15, 04318 Leipzig, Germany. Electronic address: ralph.kuehne@ufz.de. IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Environmental Chemistry and Toxicology Laboratory, via La Masa 19, 20156 Milan, Italy. Electronic address: anna.lombardo@marionegri.it. ETH Zurich, Wolfgang-Pauli-Str. 10, 8093 Zurich, Switzerland. UFZ Department of Ecological Chemistry, Helmholtz Centre for Environmental Research, Permoserstr. 15, 04318 Leipzig, Germany; Institute for Organic Chemistry, Technical University Bergakademie Freiberg, Leipziger Strasse 29, 09596 Freiberg, Germany. Electronic address: gerrit.schuurmann@ufz.de" |
| DOI: | 10.1016/j.scitotenv.2017.10.317 |
| ISSN/ISBN: | 1879-1026 (Electronic) 0048-9697 (Linking) |
| Abstract: | "Aquatic bioconcentration factors (BCFs) are critical in PBT (persistent, bioaccumulative, toxic) and risk assessment of chemicals. High costs and use of more than 100 fish per standard BCF study (OECD 305) call for alternative methods to replace as much in vivo testing as possible. The BCF waiving scheme is a screening tool combining QSAR classifications based on physicochemical properties related to the distribution (hydrophobicity, ionisation), persistence (biodegradability, hydrolysis), solubility and volatility (Henry's law constant) of substances in water bodies and aquatic biota to predict substances with low aquatic bioaccumulation (nonB, BCF<2000). The BCF waiving scheme was developed with a dataset of reliable BCFs for 998 compounds and externally validated with another 181 substances. It performs with 100% sensitivity (no false negatives), >50% efficacy (waiving potential), and complies with the OECD principles for valid QSARs. The chemical applicability domain of the BCF waiving scheme is given by the structures of the training set, with some compound classes explicitly excluded like organometallics, poly- and perfluorinated compounds, aromatic triphenylphosphates, surfactants. The prediction confidence of the BCF waiving scheme is based on applicability domain compliance, consensus modelling, and the structural similarity with known nonB and B/vB substances. Compounds classified as nonB by the BCF waiving scheme are candidates for waiving of BCF in vivo testing on fish due to low concern with regard to the B criterion. The BCF waiving scheme supports the 3Rs with a possible reduction of >50% of BCF in vivo testing on fish. If the target chemical is outside the applicability domain of the BCF waiving scheme or not classified as nonB, further assessments with in silico, in vitro or in vivo methods are necessary to either confirm or reject bioaccumulative behaviour" |
| Keywords: | "Animals Ecotoxicology/*methods *Environmental Monitoring *Fishes *Food Chain Hydrophobic and Hydrophilic Interactions Quantitative Structure-Activity Relationship Risk Assessment Water Pollutants, Chemical/*analysis (Bio)degradability 3Rs BCF waiving sche;" |
| Notes: | "MedlineNendza, Monika Kuhne, Ralph Lombardo, Anna Strempel, Sebastian Schuurmann, Gerrit eng Netherlands 2017/11/07 Sci Total Environ. 2018 Mar; 616-617:97-106. doi: 10.1016/j.scitotenv.2017.10.317. Epub 2017 Nov 4" |
