Hidden drivers of low-dose pharmaceutical pollutant mixtures revealed by the novel GSA-QHTS screening method.
The ecological impacts of emerging pollutants such as pharmaceuticals are not well understood. The lack of experimental approaches for the identification of pollutant effects in realistic settings (that is, low doses, complex mixtures, and variable environmental conditions) supports the widespread perception that these effects are often unpredictable. To address this, we developed a novel screening method (GSA-QHTS) that couples the computational power of global sensitivity analysis (GSA) with the experimental efficiency of quantitative high-throughput screening (QHTS). We present a case study where GSA-QHTS allowed for the identification of the main pharmaceutical pollutants (and their interactions), driving biological effects of low-dose complex mixtures at the microbial population level. The QHTS experiments involved the integrated analysis of nearly 2700 observations from an array of 180 unique low-dose mixtures, representing the most complex and data-rich experimental mixture effect assessment of main pharmaceutical pollutants to date. An ecological scaling-up experiment confirmed that this subset of pollutants also affects typical freshwater microbial community assemblages. Contrary to our expectations and challenging established scientific opinion, the bioactivity of the mixtures was not predicted by the null mixture models, and the main drivers that were identified by GSA-QHTS were overlooked by the current effect assessment scheme. Our results suggest that current chemical effect assessment methods overlook a substantial number of ecologically dangerous chemical pollutants and introduce a new operational framework for their systematic identification.
Department of Agricultural and Biological Engineering, University of Florida, Gainesville, FL 32611, USA; Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Ismael
0000-0002-4630-7345
I
Rodea-Palomares
Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Miguel
M
Gonzalez-Pleiter
Departamento de Ingeniería Química, Universidad de Alcalá, Alcalá de Henares, 28871 Madrid, Spain.
Soledad
S
Gonzalo
Departamento de Ingeniería Química, Universidad de Alcalá, Alcalá de Henares, 28871 Madrid, Spain.
Roberto
R
Rosal
Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Francisco
0000-0002-1019-2291
F
Leganes
Institut Català de Recerca de l'Aigua, Carrer d'Emili Grafhit, 101, 17003 Girona, Spain.; Instituto de Ecología Acuática, Universidad de Girona, Campus de Montilivi, 17071 Girona, Spain.
Sergi
0000-0003-3730-0261
S
Sabater
Institut Català de Recerca de l'Aigua, Carrer d'Emili Grafhit, 101, 17003 Girona, Spain.
Maria
M
Casellas
Department of Agricultural and Biological Engineering, University of Florida, Gainesville, FL 32611, USA.
Rafael
0000-0003-2838-1514
R
Muñoz-Carpena
Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Francisca
0000-0002-7444-7601
F
Fernández-Piñas
D001419:Bacteria / Q000187:drug effects; D064420:Drug-Related Side Effects and Adverse Reactions; D004784:Environmental Monitoring; D004785:Environmental Pollutants / Q000302:isolation & purification* / Q000633:toxicity; D057166:High-Throughput Screening Assays; D006801:Humans; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000302:isolation & purification*; D014874:Water Pollutants, Chemical / Q000302:isolation & purification* / Q000633:toxicity
D004785:Environmental Pollutants; D004364:Pharmaceutical Preparations; D014874:Water Pollutants, Chemical
GSA; Pollution; QHTS; complexity; freshwaters; low-dose; microorganisms; mixtures; pharmaceuticals