title: Quantitative structure-property relationships for predicting sorption of pharmaceuticals to sewage sludge during waste water treatment processes.
abstract: Understanding the sorption of pharmaceuticals to sewage sludge during waste water treatment processes is important for understanding their environmental fate and in risk assessments. The degree of sorption is defined by the sludge/water partition coefficient (Kd). Experimental Kdvalues (n=297) for active pharmaceutical ingredients (n=148) in primary and activated sludge were collected from literature. The compounds were classified by their charge at pH7.4 (44 uncharged, 60 positively and 28 negatively charged, and 16 zwitterions). Univariate models relating log Kdto log Kowfor each charge class showed weak correlations (maximum R2=0.51 for positively charged) with no overall correlation for the combined dataset (R2=0.04). Weaker correlations were found when relating log Kdto log Dow. Three sets of molecular descriptors (Molecular Operating Environment, VolSurf and ParaSurf) encoding a range of physico-chemical properties were used to derive multivariate models using stepwise regression, partial least squares and Bayesian artificial neural networks (ANN). The best predictive performance was obtained with ANN, with R2=0.62-0.69 for these descriptors using the complete dataset. Use of more complex Vsurf and ParaSurf descriptors showed little improvement over Molecular Operating Environment descriptors. The most influential descriptors in the ANN models, identified by automatic relevance determination, highlighted the importance of hydrophobicity, charge and molecular shape effects in these sorbate-sorbent interactions. The heterogeneous nature of the different sewage sludges used to measure Kdlimited the predictability of sorption from physico-chemical properties of the pharmaceuticals alone. Standardization of test materials for the measurement of Kdwould improve comparability of data from different studies, in the long-term leading to better quality environmental risk assessments.
authors.affiliation: AstraZeneca Global Environment, Alderley Park, Macclesfield SK10 4TG, UK; School of Pharmacy and Biomedical Sciences, University of Portsmouth, St Michael's Building, White Swan Road, Portsmouth, Hampshire PO1 2DT, UK.
authors.forename: L
authors.initials: L
authors.lastname: Berthod
authors.affiliation: School of Pharmacy and Biomedical Sciences, University of Portsmouth, St Michael's Building, White Swan Road, Portsmouth, Hampshire PO1 2DT, UK. Electronic address: david.whitley@port.ac.uk.
authors.forename: D C
authors.initials: DC
authors.lastname: Whitley
authors.affiliation: AstraZeneca Global Environment, Alderley Park, Macclesfield SK10 4TG, UK.
authors.forename: G
authors.initials: G
authors.lastname: Roberts
authors.affiliation: AstraZeneca Global Environment, Alderley Park, Macclesfield SK10 4TG, UK.
authors.forename: A
authors.initials: A
authors.lastname: Sharpe
authors.affiliation: School of Biological Sciences, University of Portsmouth, King Henry Building, King Henry I Street, Portsmouth, Hampshire PO1 2DY, UK.
authors.forename: R
authors.initials: R
authors.lastname: Greenwood
authors.affiliation: School of Pharmacy and Biomedical Sciences, University of Portsmouth, St Michael's Building, White Swan Road, Portsmouth, Hampshire PO1 2DT, UK.
authors.forename: G A
authors.initials: GA
authors.lastname: Mills
mesh_terms: D000327:Adsorption; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D012722:Sewage / Q000737:chemistry*; D014865:Waste Disposal, Fluid; D062065:Wastewater / Q000737:chemistry*; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000737:chemistry*
chemical_list: D004364:Pharmaceutical Preparations; D012722:Sewage; D062065:Wastewater; D014874:Water Pollutants, Chemical
keywords: Artificial neural networks; Partition coefficient; Pharmaceuticals; Quantitative structure-property relationship (QSPR); Sewage sludge; Sorption