The presence of drugs in the environment is an emerging issue in the scientific community. It has been shown that these substances are active chemicals that consequently affect aquatic organisms and, finally, humans as end users. To evaluate the toxicity of these compounds and how they affect the environment, it is important to perform systematic ecotoxicological and physicochemical studies. The best way to address this problem is to conduct studies on different aquatic trophic levels. In this work, an ecotoxicological study of six drugs (anhydrous caffeine, diphenhydramine hydrochloride, gentamicin sulphate, lidocaine hydrochloride, tobramycin sulphate and enalapril maleate) that used three aquatic biological models (Raphidocelis subcapitata, Aliivibrio fischeri and Daphnia magna) was performed. Additionally, the concentration of chlorophyll in the algae R. subcapitata was measured. Furthermore, EC50 values were analysed using the Passino and Smith classification (PSC) method, which categorized the compounds as toxic or relatively toxic. All of the studied drugs showed clear concentration-dependent toxic effects. The toxicity of the chemicals depended on the biological model studied, with Raphidocelis subcapitata being the most sensitive species and Aliivibrio fischeri being the least sensitive. The results indicate that the most toxic compound, for all the studied biological models, was diphenhydramine hydrochloride.
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Abbas M, Adil M, Ehtisham-ul-Haque S, Munir B, Yameen M, Ghaffar A, Shar GA, Tahir MA, Iqbal M (2018) Vibrio fischeri bioluminescence inhibition assay for ecotoxicity assessment: a review. Sci Total Environ 626:1295–1309
Araujo GS, Pinheiro C, Pestana JLT, Soares AMVM, Abessa DMS, Loureiro S (2019) Toxicity of lead and mancozeb differs in two monophyletic Daphnia species. Ecotox Environ Safe 178:230–238
Arnnok P, Singh RR, Burakham R, Perez-Fuentetaja A, Aga DS (2017) Selective uptake and bioaccumulation of antidepressants in fish from effluent-impacted Niagara River. Environ Sci Technol 51:10652–10662
Ashfaq M, Li Y, Rehman MSU, Zubair M, Mustafa G, Nazar MF, Yu CP, Sun Q (2019) Occurrence, spatial variation and risk assessment of pharmaceuticals and personal care products in urban wastewater, canal surface water, and their sediments: a case study of Lahore, Pakistan. Sci Total Environ 688:653–663
Bars R, Fegert I, Gross M, Lewis D, Weltje L, Weyers A, Wheeler JR, Galay-Burgos M (2012) Risk assessment of endocrine active chemicals: identifying chemicals of regulatory concern. Regul Toxicol Pharmacol 64:143–154
Berninger JP, Du BW, Connors KA, Eytcheson SA, Kolkmeier MA, Prosser KN, Valenti TW, Chambliss CK, Brooks BW (2011) Effects of the antihistamine diphendydramine on selected aquatic organisms. Environ Toxicol Chem 30:2065–2072
Bernot MJ, Becker JC, Doll J, Lauer TE (2016) A national reconnaissance of trace organic compounds (TOCs) in United States lotic ecosystems. Sci Total Environ 572:422–433
Borova VL, Maragou NC, Gago-Ferrero P, Pistos C, Thomaidis NS (2014) Highly sensitive determination of 68 psychoactive pharmaceuticals, illicit drugs, and related human metabolites in wastewater by liquid chromatography-tandem mass spectrometry. Anal Bioanal Chem 406:4273–4285
Callahan SM, Cornell NW, Dunlap PV (1995) Purification and properties of periplasmic 3'/5'-cyclic nucleotide phosphodiesterase- a novel zinc-containing enzyme from the marine symbiotic bacterium vibrio fischeri. J Biol Chem 270:17627–17632
Calow P (1997) Handbook of ecotoxicology. John Wiley& Sons, Chichester
Carvalho FD, Machado I, Martinez MS, Soares A, Guilhermino L (2003) Use of atropine-treated Daphnia magna survival for detection of environmental contamination by acetylcholinesterase inhibitors. Ecotox Environ Safe 54:43–46
Connors et al (2019) Creation of a Curated Aquatic Toxicology Database: EnviroTox. Environ Toxicol Chem 38(5), 1062–1073.
Dale MP, Causton DR (1992) Use of the chlorophyll A-B ratio as a bioassay for the light environment of a plant. Funct Ecol 6:190–196
Danner MC, Robertson A, Behrends V, Reiss J (2019) Antibiotic pollution in surface fresh waters: occurrence and effects. Sci Total Environ 664:793–804
de Vasconcelos EC, Dalke CR, de Oliveira CMR (2017) Influence of select antibiotics on Vibrio fischeri and Desmodesmus subspicatus at mu g L-1 concentrations. Environ Manag 60:157–164
DeYoung DJ, Bantle JA, Hull MA, Burks SL (1996) Differences in sensitivity to developmental toxicants as seen in Xenopus and Pimephales embryos. B Environ Contam Tox 56:143–150
Di Poi C, Costil K, Bouchart V, Halm-Lemeille MP (2018) Toxicity assessment of five emerging pollutants, alone and in binary or ternary mixtures, towards three aquatic organisms. Environ Sci Pollut R 25:6122–6134
Elliott SM, Brigham ME, Lee KE, Banda JA, Choy SJ, Gefell DJ, Minarik TA, Moore JN, Jorgenson ZG (2017) Contaminants of emerging concern in tributaries to the Laurentian Great Lakes: I. Patterns of occurrence. Plos One 12
Fekadu S, Alemayehu E, Dewil R, Van der Bruggen B (2019) Pharmaceuticals in freshwater aquatic environments: a comparison of the African and European challenge. Sci Total Environ 654:324–337
Fournier D, Luft FC, Bader M, Ganten D, Andrade-Navarro MA (2012) Emergence and evolution of the renin-angiotensin-aldosterone system. J Mol Med 90:495–508
Garcia-Ac A, Segura PA, Gagnon C, Sauve S (2009) Determination of bezafibrate, methotrexate, cyclophosphamide, orlistat and enalapril in waste and surface waters using on-line solid-phase extraction liquid chromatography coupled to polarity-switching electrospray tandem mass spectrometry. J Environ Monitor 11:830–838
Geiger JG, Buikema AL (1981) Oxygen-consumption and filtering rate of daphnia-pulex after exposure to water-soluble fractions of naphtalene, phenanthrene, NO2 fuel oil, and coal-tar creosote. B Environ Contam Tox 27:783–789
Geiger D, Poirier S, Brooke L, Call D (1986) Acute toxicities of organic chemicals to fathead minnows (Pimephales promelas): Volume III University of Wisconsin-Superior, Center for Lake Superior Environmental Studies
Gunnarsson L, Jauhiainen A, Kristiansson E, Nerman O, Larsson DGJ (2008) Evolutionary conservation of human drug targets in organisms used for environmental risk assessments. Environ Sci Technol 42:5807–5813
Gunnarsson L, Snapk JR, Verbruggen B, Owen SF, Kristiansson E, Margiotta-Casaluci L, Osterlund T, Hutchinson K, Leverett D, Marks B, Tyler CR (2019) Pharmacology beyond the patient - the environmental risks of human drugs. Environ Int 129:320–332
Gutierrez JB (2001) Fundamentos de ciencia toxicológica. Ediciones Díaz de Santos, Madrid ALdCS
Hayes AW, Kruger CL (2014) Principles and methods of toxicology. CRC Press, Boca Raton
Institue of Medicine (U.S) CoMNR (2001) Caffeine for the sustainment of mental task performance: formulations for military operations. National Academy Press, Washington, D.C.
Ioele G, De Luca M, Ragno G (2016) Acute toxicity of antibiotics in surface waters by bioluminescence test. Curr Pharm Anal 12:220–226
Jafari M, Keshavarz MH, Salek H (2019) A simple method for assessing chemical toxicity of ionic liquids on Vibrio fischeri through the structure of cations with specific anions. Ecotox Environ Safe 182:109429
Jaukovic ZD, Grujic SD, Vasiljevic TM, Petrovic SD, Lausevic MD (2014) Cardiovascular drugs in environmental waters and wastewaters: method optimization and real sample analysis. J AOAC Int 97:1167–1174
Jennings VLK, Rayner-Brandes MH, Bird DJ (2001) Assessing chemical toxicity with the bioluminescent photobacterium (Vibrio fischeri): a comparison of three commercial systems. Water Res 35:3448–3456
Johansen MN (2012) Microalgae: biotechnology, microbiology and energy. Nova Science Publishers, New York
Jureczko M, Przystas W (2019) Ecotoxicity risk of presence of two cytostatic drugs: bleomycin and vincristine and their binary mixture in aquatic environment. Ecotox Environ Safe 172:210–215
Kang YM, Kim MK, Kim T, Kim TK, Zoh KD (2019) Occurrence and fate of micropollutants in private wastewater treatment facility (WTF) and their impact on receiving water. Environ Manage 64:650–660
Kümmerer K (2008) Pharmaceuticals in the environment : sources, fate. Springer, Effects and Risks
Lagesson A, Fahlman J, Brodin T, Fick J, Jonsson M, Bystrom P, Klaminder J (2016) Bioaccumulation of five pharmaceuticals at multiple trophic levels in an aquatic food web - insights from a field experiment. Sci Total Environ 568:208–215
Li M, Wei DB, Du YG (2014) Acute toxicity evaluation for quinolone antibiotics and their chlorination disinfection processes. J Environ Sci-China 26:1837–1842
Liang P, Jones CA, Bisgrove BW, Song L, Glenn ST, Yost HJ, Gross KW (2004) Genomic characterization and expression analysis of the first nonmammalian renin genes from zebrafish and pufferfish. PhysiolGenomics 16:314–322
Lichtenthaler HK (1987) Chlorophylls and carotenoids-pigments of photosynthetic biomembranes. Method Enzymol 148:350–382
Lilius H, Isomaa B, Holmstrom T (1994) A comparison of the toxicity of 50 reference chemicals to freshly isolated rainbow-trout hepatocytes and Daphnia magna. Aquat Toxicol 30:47–60
Liu B, Liu W, Nie X, Guan C, Yang Y, Wang Z, Liao W (2011) Growth response and toxic effects of three antibiotics on Selenastrum capricornutum evaluated by photosynthetic rate and chlorophyll biosynthesis. J Environ Sci 23:1558–1563
Lomba L, Pilar Ribate M, Zuriaga E, Garcia CB, Giner B (2019) Acute and subacute effects of drugs in embryos of Danio rerio. QSAR grouping and modelling. Ecotox Environ Safe 172:232–239
Lopez-Pacheco IY, Silva-Nunez A, Salinas-Salazar C, Arevalo-Gallegos A, Lizarazo-Holguin LA, Barcelo D, Iqbal HMN, Parra-Saldivar R (2019) Anthropogenic contaminants of high concern: existence in water resources and their adverse effects. Sci Total Environ 690:1068–1088
McCormick PV, Cairns J (1994) Algae as indicators of environmental change. J Appl Phycol 6:509–526
Meinertz JR, Schreier TM, Bernardy JA, Franz JL (2010) Chronic toxicity of diphenhydramine hydrochloride and erythromycin thiocyanate to Daphnia, Daphnia magna, in a continuous exposure test system. B Environ Contam Tox 85:447–451
Melis A, Harvey GW (1981) Regulation of photosystem stoichiometry, chlorophyll A and chlorophyll B content and relation to chloroplast ultrastructure. Biochim Biophys Acta 637:138–145
Misik M, Filipic M, Nersesyan A, Kundi M, Isidori M, Knasmueller S (2019) Environmental risk assessment of widely used anticancer drugs (5-fluorouracil, cisplatin, etoposide, imatinib mesylate). Water Res 164:114953
Neuwoehner J, Escher BI (2011) The pH-dependent toxicity of basic pharmaceuticals in the green algae Scenedesmus vacuolatus can be explained with a toxicokinetic ion-trapping model. Aquat Toxicol 101:266–275
Nie X, Gu J, Lu J, Pan W, Yang Y (2009) Effects of norfloxacin and butylated hydroxyanisole on the freshwater microalga Scenedesmus obliquus. Ecotoxicology 18:677–684
OECD 201 Guideline for testing of chemicals (1984) Alga, Growth Inhibition Test
OECD 202 Guideline for testing of chemicals (1984) Daphnia sp, Acute Inmobilisation test and Reproduction test
Onorati F, Mecozzi M (2004) Effects of two diluents in the Microtox (R) toxicity bioassay with marine sediments. Chemosphere 54:679–687
Park S, Choi K (2008) Hazard assessment of commonly used agricultural antibiotics on aquatic ecosystems. Ecotoxicology 17:526–538
Passino DRM, Smith SB (1987) Acute bioassays and hazard evaluation of representative contaminants detected in great-lakes fish. Environ Toxicol Chem 6:901–907
Pomati F, Rossetti C, Calamari D, Neilan BA (2003) Effects of saxitoxin (STX) and veratridine on bacterial Na+-K+ fluxes: a prokaryote-based STX bioassay. Appl Environ Microb 69:7371–7376
Rivetti C et al (2015) Transcriptomic, biochemical and individual markers in transplanted Daphnia magna to characterize impacts in the field. Sci Total Environ 503:200–212
Roberts J, Kumar A, Du J, Hepplewhite C, Ellis DJ, Christy AG, Beavis SG (2016) Pharmaceuticals and personal care products (PPCPs) in Australia’s largest inland sewage treatment plant, and its contribution to a major Australian river during high and low flow. Sci Total Environ 541:1625–1637
Ros N, Lomba L, Pilar Ribate M, Zuriaga E, Garcia CB, Giner B (2018) Acute lethal and sublethal effects of diltiazem and doxepin for four aquatic environmental bioindicators covering the trophic chain. AIMS Environ Sci 5:229–243
Rosa Souza LR, Bernardes LE, Santos Barbetta MF, Mesquita Silva da Veiga MA (2019) Iron oxide nanoparticle phytotoxicity to the aquatic plant Lemna minor: effect on reactive oxygen species (ROS) production and chlorophyll a/chlorophyll b ratio. Environ Sci Pollut R 26:24121–24131
Selderslaghs IWT, Blust R, Witters HE (2012) Feasibility study of the zebrafish assay as an alternative method to screen for developmental toxicity and embryotoxicity using a training set of 27 compounds. Reprod Toxicol 33:142–154
Steinkey D, Lari E, Woodman SG, Steinkey R, Luong KH, Wong CS, Pyle GG (2019) The effects of diltiazem on growth, reproduction, energy reserves, and calcium-dependent physiology in Daphnia magna. Chemosphere 232:424–429
Taylor G, Baird DJ, Soares A (1998) Surface binding of contaminants by algae: consequences for lethal toxicity and feeding to Daphnia magna Straus. Environ Toxicol Chem 17:412–419
Tian Y, Xia X, Wang J, Zhu L, Wang J, Zhang F, Ahmad Z (2019) Chronic toxicological effects of carbamazepine on Daphnia magna Straus: effects on reproduction traits, body length, and intrinsic growth. B environ contam tox 103:723–728
Ullrich SO, Millemann RE (1983) Survival, respiration, and food assimilation of Daphnia magna exposed to petroleum derived and coal-derived oils at three temperatures. Can J Fish Aquat Sci 40:17–26
UNE-EN ISO 11348-3 (2009) Water quality. Determination of the inhibitory effect of water samples on the light emission of Vibrio fischeri (luminiscent bacteria test)- Part 3: method using freeze-dried bacteria
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M (2018): DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res 4, D1074-D1082.
Yang ZP, Lu T, Zhu YC, Zhang Q, Zhou ZG, Pan XL, Qian HF (2019) Aquatic ecotoxicity of an antidepressant, sertraline hydrochloride, on microbial communities. Sci Total Environ 654:129–134
Zhang L, Baer KN (2000) The influence of feeding, photoperiod and selected solvents on the reproductive strategies of the water flea, Daphnia magna. Environ Pollut 110:425–430
Zhang YG, Guo J, Yao TM, Zhang YL, Zhou XF, Chu HQ (2019a) The influence of four pharmaceuticals on Chlorellapyrenoidosa culture. Sci Rep 9
Zhang YX, Guo PY, Wu YM, Zhang XY, Wang MX, Yang SM, Sun YS, Deng J, Su HT (2019b) Evaluation of the subtle effects and oxidative stress response of chloramphenicol, thiamphenicol, and florfenicol in Daphnia magna. EnvironToxicol Chem 38:575–584
Zhou S, Di Paolo C, Wu X, Shao Y, Seiler T-B, Hollert H (2019) Optimization of screening-level risk assessment and priority selection of emerging pollutants - the case of pharmaceuticals in European surface waters. Environ Int 128:1–10
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• Ecotoxicological study of six drugs in three aquatic biomodels
• The most sensitive biological model to these pharmaceuticals was R. subcapitata.
• The most toxic drug studied for the environment was diphenhydramine hydrochloride.
Responsible editor: Philippe Garrigues
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Lomba, L., Lapeña, D., Ros, N. et al. Ecotoxicological study of six drugs in Aliivibrio fischeri, Daphnia magna and Raphidocelis subcapitata. Environ Sci Pollut Res (2020). https://doi.org/10.1007/s11356-019-07592-8
- Aliivibrio fischeri
- Daphnia magna
- Raphidocelis subcapitata