title: Ranking of concern, based on environmental indexes, for pharmaceutical and personal care products: an application to the Spanish case.
abstract: A wide range of Pharmaceuticals and Personal Care Products (PPCPs) are present in the environment, and many of their adverse effects are unknown. The emergence of new compounds or changes in regulations have led to dynamical studies of occurrence, impact and treatment, which consider geographical areas and trends in consumption and innovation in the pharmaceutical industry. A Quantitative study of Structure-Activity Relationship ((Q)SAR) was performed to assess the possible adverse effects of ninety six PPCPs and metabolites with negligible experimental data and establish a ranking of concern, which was supported by the EPA EPI Suite™ interface. The environmental and toxicological indexes, the persistence (P), the bioaccumulation (B), the toxicity (T) (extensive) and the occurrence in Spanish aquatic environments (O) (intensive) were evaluated. The most hazardous characteristics in the largest number of compounds were generated by the P index, followed by the T and B indexes. A high number of metabolites has a concern score equal to or greater than their parent compounds. Three PBT and OPBT rankings of concern were proposed using the total and partial ranking method (supported by a Hasse diagram) by the Decision Analysis by Ranking Techniques (DART) tool, which was recently recommended by the European Commission. An analysis of the sensibility of the relative weights of these indexes has been conducted. Hormones, antidepressants (and their metabolites), blood lipid regulators and all of the personal care products considered in this study were at the highest levels of risk according to the PBT and OPBT total rankings. Furthermore, when the OPBT partial ranking was performed, X-ray contrast media, H2 blockers and some antibiotics were included at the highest level of concern. It is important to improve and incorporate useful indexes for the predicted environmental impact of PPCPs and metabolites and thus focus experimental analysis on the compounds that require urgent attention.
authors.affiliation: Department of Chemical Engineering and Environmental Technology, University of Valladolid, Calle Dr. Mergelina s/n, 47011 Valladolid, Spain(1); Department of Chemistry, Faculty of Sciences and Technology, University of Carabobo, Av. Salvador Allende, Campus Bárbula, Carabobo, Bolivarian Republic of Venezuela(3). Electronic address: sheyla.ortiz@iq.uva.es.
authors.forename: Sheyla
authors.initials: S
authors.lastname: Ortiz de García
authors.forename: Gilberto Pinto
authors.initials: GP
authors.lastname: Pinto
authors.forename: Pedro A
authors.initials: PA
authors.lastname: García-Encina
authors.forename: Rubén I
authors.initials: RI
authors.lastname: Irusta Mata
mesh_terms: D064420:Drug-Related Side Effects and Adverse Reactions; D004784:Environmental Monitoring / Q000379:methods*; D006795:Household Products / Q000032:analysis / Q000633:toxicity*; D008962:Models, Theoretical; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D013030:Spain; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000378:metabolism / Q000633:toxicity*
chemical_list: D004364:Pharmaceutical Preparations; D014874:Water Pollutants, Chemical
keywords: (Q)SARs; ATC; B; BCF; BIOWIN™; Bioaccumulation; CAS; ChV; DART; Decision Analysis by Ranking Techniques; ECOSAR; EMEA; EPA EPI Suite™; ERA; Environmental Risk Assessment; Estimation Programs Interface Suite™ developed by the EPA's Office of Pollution Prevention Toxics and Syracuse Research Corporation; European Medicines Agency; European Regulation for Registration Evaluation Authorization and Restriction of Chemicals; LC; NOEC; NSAIDs; O; OECD; Occurrence; Organization for Economic Co-operation and Development; P; PCPs; PECs; PERs; PNEC; POR; PPCPs; Persistence; Personal Care Products; PhACs; Pharmaceutical and Personal Care products; Pharmaceutical and personal care products; Pharmaceutically Active Compounds; Quantitative Structure–Activity Relationships; REACH; Ranking; SARs; SMILES; SRC; Simplified Molecular Input Line Entry System; Structure–Activity Relationships; Syracuse Research Corporation; T; Therapeutic Chemical Classification System; Toxicity; US EPA; US EPA ecological structure–activity relationship; United States Environmental Protection Agency; WWTP; Wastewater Treatment Plant; bioaccumulation; bioconcentration factor; chemical abstracts; chronic toxicity; level of concern; no-observed effect concentration; non-steroidal anti-inflammatory drugs; occurrence; partial order ranking; persistence; physical–chemical property estimation routines; predicted environmental concentrations; predicted no effect concentration; software by US EPA for estimates probability of rapid aerobic and anaerobic biodegradation