Occurrence of immunosuppressive drugs and their metabolites in the sewage-impacted Vistula and Utrata Rivers and in tap water from the Warsaw region (Poland)

Chemosphere

Volume 148, April 01, 2016, Pages 137-147

Giebułtowicz, J.^a , 

Nałecz-Jawecki, G.^b 

^a  Department of Bioanalysis and Drugs Analysis, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Street, Warsaw, Poland
^b  Department of Environmental Health Sciences, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Street, Warsaw, Poland 

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Abstract

Immunosuppresive therapy following organ transplant frequently includes treatment with tacrolimus and mycophenolic acid derivatives. These pharmaceuticals may enter the environment through wastewater treatment plant (WWTP) effluents and may have a potentially harmful effect on aquatic biota. Tacrolimus, mycophenolic acid and their metabolites were measured at specific points of a large Polish river (Vistula), a smaller river (Utrata) and in tap water samples from the Warsaw region. Analysis was performed using liquid chromatography tandem mass spectrometry, after solid phase extraction for water samples, or QuEChERS extraction for sediments. Residues of tacrolimus were below quantitation limits in both water and sediment samples. However, in water samples mycophenolic acid concentrations were measured at up to 180 ng L^-1 downstream of WWTP outfalls. No immunosuppressive drugs were detected in tap water. Concentrations of mycophenolic acid exceeded the predicted no effect concentration (PNEC) value in some Polish surface water, and risk calculations predicted at least twice higher concentrations in some other countries of the European Union. To the best of the authors' knowledge, this is the first report of these immunosuppressive drug concentrations in the environment. © 2016 Elsevier Ltd.

Author keywords

Immunosuppressive drugs; Mycophenolic acid; Sediments; Surface water; Tacrolimus; WWTP

ISSN: 00456535 CODEN: CMSHASource Type: Journal Original language: English

DOI: 10.1016/j.chemosphere.2015.12.135Document Type: Article

Publisher: Elsevier Ltd

References (45)

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• 
  1

  Ågerstrand, M., Rudén, C.

  Evaluation of the accuracy and consistency of the Swedish Environmental Classification and Information System for pharmaceuticals
  (2010) Science of the Total Environment, 408 (11), pp. 2327-2339. Cited 16 times.
  doi: 10.1016/j.scitotenv.2010.02.020
  
• 
  2

  Barbarino, J.M., Staatz, C.E., Venkataramanan, R., Klein, T.E., Altman, R.B.

  PharmGKB summary: Cyclosporine and tacrolimus pathways
  (2013) Pharmacogenetics and Genomics, 23 (10), pp. 563-585. Cited 17 times.
  doi: 10.1097/FPC.0b013e328364db84
  
• 
  3

  Borzecka, I., Buras, P., Szlakowski, J., Gasinski, Z., Wisniewolski, W.
  The fish fauna in selected rivers of the Mazovian Lowland
  (2012) Fragm. Faun., 55 (1), pp. 75-90. Cited 2 times.
  

  •  
• 
  4

  Chitnis, S.D., Ogasawara, K., Schniedewind, B., Gohh, R.Y., Christians, U., Akhlaghi, F.

  Concentration of tacrolimus and major metabolites in kidney transplant recipients as a function of diabetes mellitus and cytochrome P450 3A gene polymorphism
  (2013) Xenobiotica, 43 (7), pp. 641-649. Cited 7 times.
  doi: 10.3109/00498254.2012.752118
  
• 
  5

  Clift, D.E., Thorn, R.J., Passarelli, E.A., Kapoor, M., LoPiccolo, M.K., Richendrfer, H.A., Colwill, R.M., (...), Creton, R.

  Effects of embryonic cyclosporine exposures on brain development and behavior
  (2015) Behavioural Brain Research, 282, pp. 117-124. Cited 4 times.
  www.elsevier.com/locate/bbr
  doi: 10.1016/j.bbr.2015.01.006
  
• 
  6

  (2008) Guidance on Information Requirements and Chemical Safety Assessment. Cited 152 times.
  European Chemical Agency
  https://echa.europa.eu/documents/10162/13632/information_requirements_r10_en.pdf
  

  •  
• 
  7

  (2006) European Medicines Agency/Committee for Medicinal Products for Human Use. Guideline for the Environmental Risk Assessment of Medicinal Products for Human Use
  EMEA, London, UK
  

  •  
• 
  8

  (1998) Fate, Transport and Transformation Test Guidelines. OPPTS 835.2210 Direct Photolysis Rate in Water by Sunlight. Cited 22 times.
  Environmental Protection Agency, United States
  

  •  
• 
  9

  (2015) Estimation Programs Interface Suite™ for Microsoft^® Windows
  United States Environmental Protection Agency, Washington, DC, USA
  

  •  
• 
  10

  (2015) The Swedish Medicines Information Engine
  CellCept. Roche. Environmental impact
  http://www.fass.se/LIF/product?userType=0&nplId=19960214000013&docType=78&scrollTopPosition=313&docTypeDynTab=78
  

  •  
• 
  11

  Ferrando-Climent, L., Rodriguez-Mozaz, S., Barceló, D.

  Incidence of anticancer drugs in an aquatic urban system: From hospital effluents through urban wastewater to natural environment
  (2014) Environmental Pollution, 193, pp. 216-223. Cited 17 times.
  www.elsevier.com/inca/publications/store/4/0/5/8/5/6
  doi: 10.1016/j.envpol.2014.07.002
  
• 
  12

  Franquet-Griell, H., Gómez-Canela, C., Ventura, F., Lacorte, S.

  Predicting concentrations of cytostatic drugs in sewage effluents and surface waters of Catalonia (NE Spain)
  (2015) Environmental Research, 138, pp. 161-172. Cited 4 times.
  http://www.elsevier.com/inca/publications/store/6/2/2/8/2/1/index.htt
  doi: 10.1016/j.envres.2015.02.015
  
• 
  13

  Fredriksson, N.J., Hermansson, M., Wilén, B.-M.

  Diversity and dynamics of Archaea in an activated sludge wastewater treatment plant
  (2012) BMC Microbiology, 12, art. no. 140. Cited 10 times.
  doi: 10.1186/1471-2180-12-140
  
• 
  14

  Gao, X.-P., Feng, F., Zhang, X.-Q., Liu, X.-X., Wang, Y.-B., She, J.-X., He, Z.-H., (...), He, M.-F.

  Toxicity assessment of 7 anticancer compounds in zebrafish
  (2014) International Journal of Toxicology, 33 (2), pp. 98-105. Cited 5 times.
  http://ijt.sagepub.com/
  doi: 10.1177/1091581814523142
  
• 
  15

  Giebułtowicz, J., Nałecz-Jawecki, G.

  Occurrence of antidepressant residues in the sewage-impacted Vistula and Utrata rivers and in tap water in Warsaw (Poland)
  (2014) Ecotoxicology and Environmental Safety, 104 (1), pp. 103-109. Cited 9 times.
  http://www.elsevier.com/inca/publications/store/6/2/2/8/1/9/index.htt
  doi: 10.1016/j.ecoenv.2014.02.020
  
• 
  16

  Golovko, O., Kumar, V., Fedorova, G., Randak, T., Grabic, R.

  Removal and seasonal variability of selected analgesics/anti-inflammatory, anti-hypertensive/cardiovascular pharmaceuticals and UV filters in wastewater treatment plant
  (2014) Environmental Science and Pollution Research, 21 (12), pp. 7578-7585. Cited 13 times.
  http://www.springerlink.com/content/0944-1344
  doi: 10.1007/s11356-014-2654-9
  
• 
  17

  Grabowski, M., Bacela, K., Konopacka, A., Jazdzewski, K.

  Salinity-related distribution of alien amphipods in rivers provides refugia for native species
  (2009) Biological Invasions, 11 (9), pp. 2107-2117. Cited 25 times.
  doi: 10.1007/s10530-009-9502-8
  
• 
  18

  Hernando, M.D., Mezcua, M., Fernández-Alba, A.R., Barceló, D.

  Environmental risk assessment of pharmaceutical residues in wastewater effluents, surface waters and sediments
  (2006) Talanta, 69 (2 SPEC. ISS.), pp. 334-342. Cited 417 times.
  doi: 10.1016/j.talanta.2005.09.037
  
• 
  19

  Hyland, K.C., Dickenson, E.R.V., Drewes, J.E., Higgins, C.P.

  Sorption of ionized and neutral emerging trace organic compounds onto activated sludge from different wastewater treatment configurations
  (2012) Water Research, 46 (6), pp. 1958-1968. Cited 51 times.
  doi: 10.1016/j.watres.2012.01.012
  
• 
  20

  (2015) Institute of Meteorology and Water Management-national Research Institute in Poland. Poland. Climatic Data
  2015 Sep. 01
  http://pogodynka.pl/polska/daneklimatyczne/
  

  •  
• 
  21

  (2015) Institute of Meteorology and Water Management-national Research Institute in Poland. Water Flows in Selected Points in the Vistula Basin
  2015 Sep. 01
  http://www.pogodynka.pl/hydro/wisla/
  

  •  
• 
  22

  Iwasaki, K.

  Metabolism of tacrolimus (FK506) and recent topics in clinical pharmacokinetics.
  (2007) Drug metabolism and pharmacokinetics, 22 (5), pp. 328-335. Cited 97 times.
  doi: 10.2133/dmpk.22.328
  
• 
  23

  Ju, F., Guo, F., Ye, L., Xia, Y., Zhang, T.

  Metagenomic analysis on seasonal microbial variations of activated sludge from a full-scale wastewater treatment plant over 4 years
  (2014) Environmental Microbiology Reports, 6 (1), pp. 80-89. Cited 15 times.
  doi: 10.1111/1758-2229.12110
  
• 
  24

  Keller, V.D.J., Williams, R.J., Lofthouse, C., Johnson, A.C.

  Worldwide estimation of river concentrations of any chemical originating from sewage-treatment plants using dilution factors
  (2014) Environmental Toxicology and Chemistry, 33 (2), pp. 447-452. Cited 14 times.
  doi: 10.1002/etc.2441
  
• 
  25

  Kim, W.R., Smith, J.M., Skeans, M.A., Schladt, D.P., Schnitzler, M.A., Edwards, E.B., Harper, A.M., (...), Kasiske, B.L.

  OPTN/SRTR 2012 Annual Data Report: Liver
  (2014) American Journal of Transplantation, 14 (SUPPL. 1), pp. 69-96. Cited 65 times.
  doi: 10.1111/ajt.12581
  
• 
  26

  Kraigher, B., Kosjek, T., Heath, E., Kompare, B., Mandic-Mulec, I.

  Influence of pharmaceutical residues on the structure of activated sludge bacterial communities in wastewater treatment bioreactors
  (2008) Water Research, 42 (17), pp. 4578-4588. Cited 63 times.
  doi: 10.1016/j.watres.2008.08.006
  
• 
  27

  Lamba, V., Sangkuhl, K., Sanghavi, K., Fish, A., Altman, R.B., Klein, T.E.

  PharmGKB summary: mycophenolic acid pathway.
  (2014) Pharmacogenetics and genomics, 24 (1), pp. 73-79. Cited 4 times.
  
• 
  28

  Luo, Y., Guo, W., Ngo, H.H., Nghiem, L.D., Hai, F.I., Zhang, J., Liang, S., (...), Wang, X.C.

  A review on the occurrence of micropollutants in the aquatic environment and their fate and removal during wastewater treatment
  (2014) Science of the Total Environment, 473-474, pp. 619-641. Cited 188 times.
  www.elsevier.com/locate/scitotenv
  doi: 10.1016/j.scitotenv.2013.12.065
  
• 
  29

  Majewski, W.
  General characteristics of the Vistula and its basin
  (2013) Acta Energ., 2, pp. 6-15.
  

  •  
• 
  30

  Matas, A.J., Smith, J.M., Skeans, M.A., Thompson, B., Gustafson, S.K., Schnitzler, M.A., Stewart, D.E., (...), Kasiske, B.L.

  OPTN/SRTR 2012 Annual Data Report: Kidney
  (2014) American Journal of Transplantation, 14 (SUPPL. 1), pp. 11-44. Cited 78 times.
  doi: 10.1111/ajt.12579
  
• 
  31

  Matesanz, R.
  International figures on donation and transplantation - 2013
  (2014) Newsl. Transpl., 19, pp. 3-33.
  

  •  
• 
  32

  Möller, A., Iwasaki, K., Kawamura, A., Teramura, Y., Shiraga, T., Hata, T., Schäfer, A., (...), Undre, N.A.

  The disposition of 14C-labeled tacrolimus after intravenous and oral administration in healthy human subjects
  (1999) Drug Metabolism and Disposition, 27 (6), pp. 633-636. Cited 69 times.
  
• 
  33

  (2015) The Value of Refunds of the Prices of Medicines by EAN Code
  http://www.europeandataportal.eu/data/en/dataset/leki_refundowane/resource/ce5ebbc4-e75a-4c58-ad22-9996c4a915ae?inner_span=True
  

  •  
• 
  34

  Oakes, K.D., Coors, A., Escher, B.I., Fenner, K., Garric, J., Gust, M., Knacker, T., (...), Servos, M.R.

  Environmental risk assessment for the serotonin re uptake inhibitor fluoxetine: Case study using the european risk assessment framework
  (2010) Integrated Environmental Assessment and Management, 6 (SUPPL. 1), pp. 524-539. Cited 43 times.
  doi: 10.1002/ieam.77
  
• 
  35

  Orias, F., Perrodin, Y.

  Characterisation of the ecotoxicity of hospital effluents: A review
  (2013) Science of the Total Environment, 454-455, pp. 250-276. Cited 33 times.
  doi: 10.1016/j.scitotenv.2013.02.064
  
• 
  36

  (2015) Safety Data Sheet on Cellcept
  SECTION 12: Ecological information
  http://www.roche-australia.com/content/dam/roche_australia/en_AU/files/SDS/CELLCEPT_sds.pdf
  

  •  
• 
  37

  (2015) Material Safty Data Sheet on Mycophenolic Acid
  Section 12-Ecological information
  http://datasheets.scbt.com/sc-200110.pdf
  

  •  
• 
  38

  Santos, L.H.M.L.M., Gros, M., Rodriguez-Mozaz, S., Delerue-Matos, C., Pena, A., Barceló, D., Montenegro, M.C.B.S.M.

  Contribution of hospital effluents to the load of pharmaceuticals in urban wastewaters: Identification of ecologically relevant pharmaceuticals
  (2013) Science of the Total Environment, 461-462, pp. 302-316. Cited 74 times.
  doi: 10.1016/j.scitotenv.2013.04.077
  
• 
  39

  (2012) Stockholm County Council. Environmentally Classified Pharmaceuticals
  2015 Nov 01
  http://www.janusinfo.se/Global/Miljo_och_lakemedel/miljobroschyr_engelsk_2012_uppslag.pdf
  

  •  
• 
  40

  Stankiewicz, A., Giebułtowicz, J., Stefański, M., Sikorska, K., Wroczyński, P., Nałecz-Jawecki, G.

  The development of the LC-MS/MS method based on S-9 biotransformation for detection of metabolites of selected β-adrenolytics in surface water
  (2015) Environmental Toxicology and Pharmacology, 39 (2), pp. 906-916. Cited 2 times.
  www.elsevier.com/locate/etap
  doi: 10.1016/j.etap.2015.03.002
  
• 
  41

  Stevens-Garmon, J., Drewes, J.E., Khan, S.J., McDonald, J.A., Dickenson, E.R.V.

  Sorption of emerging trace organic compounds onto wastewater sludge solids
  (2011) Water Research, 45 (11), pp. 3417-3426. Cited 65 times.
  doi: 10.1016/j.watres.2011.03.056
  
• 
  42

  Thurman, E.M., Ferrer, I.

  Liquid chromatography/quadrupole-time-of-flight mass spectrometry with metabolic profiling of human urine as a tool for environmental analysis of dextromethorphan
  (2012) Journal of Chromatography A, 1259, pp. 158-166. Cited 9 times.
  doi: 10.1016/j.chroma.2012.03.008
  
• 
  43

  Tiehm, A., Schmidt, N., Stieber, M., Sacher, F., Wolf, L., Hoetzl, H.

  Biodegradation of Phmaceutical Compounds and their Occurrence in the Jordan Valley
  (2011) Water Resources Management, 25 (4), pp. 1195-1203. Cited 20 times.
  doi: 10.1007/s11269-010-9678-9
  
• 
  44

  Upadhyay, V., Trivedi, V., Shah, G., Yadav, M., Shrivastav, P.S.

  Determination of mycophenolic acid in human plasma by ultra performance liquid chromatography tandem mass spectrometry
  (2014) Journal of Pharmaceutical Analysis, 4 (3), pp. 205-216.
  doi: 10.1016/j.jpha.2013.06.001
  
• 
  45

  WHO Collaborating Centre for Drug Statistics Methodology
  (2015) . Cited 2 times.
  ATC/DDD Index 2016, Sept 01
  http://www.whocc.no/atc_ddd_index/
  

  •  

  Giebułtowicz, J.; Department of Bioanalysis and Drugs Analysis, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Street, Poland; email:joanna.giebultowicz@wum.edu.pl
© Copyright 2016 Elsevier B.V., All rights reserved.