Advertisement

Ecotoxicological study of six drugs in Aliivibrio fischeri, Daphnia magna and Raphidocelis subcapitata

  • Laura LombaEmail author
  • David Lapeña
  • Natalia Ros
  • Elena Aso
  • Mariachiara Cannavò
  • Diego Errazquin
  • Beatriz Giner
Research Article

Abstract

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.

Graphical abstract

Keywords

Dose-response Pharmaceuticals Aliivibrio fischeri Daphnia magna Raphidocelis subcapitata 

Notes

Funding information

Research group PLATON acknowledges the financial support from Gobierno de Aragón and Fondo Social Europeo “Construyendo Europa desde Aragón” E31_17R. Furthermore, we thank EEE53 SL and the business groups Pinares de Venecia División Energética and Brial (ENATICA) for their support. Both business groups are committed to sustainable developments through environmental respect. David Lapeña and Diego Errazquin thank Novaltia and Banco Sabadell for their financial support.

References

  1. 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 626:1295–1309CrossRefGoogle Scholar
  2. 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 178:230–238CrossRefGoogle Scholar
  3. 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 51:10652–10662CrossRefGoogle Scholar
  4. 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 688:653–663CrossRefGoogle Scholar
  5. 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 64:143–154CrossRefGoogle Scholar
  6. 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 30:2065–2072CrossRefGoogle Scholar
  7. 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 572:422–433CrossRefGoogle Scholar
  8. 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 406:4273–4285Google Scholar
  9. 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 270:17627–17632CrossRefGoogle Scholar
  10. Calow P (1997) Handbook of ecotoxicology. John Wiley& Sons, ChichesterCrossRefGoogle Scholar
  11. 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 54:43–46CrossRefGoogle Scholar
  12. Connors et al (2019) Creation of a Curated Aquatic Toxicology Database: EnviroTox. Environ Toxicol Chem 38(5), 1062–1073.CrossRefGoogle Scholar
  13. Dale MP, Causton DR (1992) Use of the chlorophyll A-B ratio as a bioassay for the light environment of a plant. Funct Ecol 6:190–196CrossRefGoogle Scholar
  14. Danner MC, Robertson A, Behrends V, Reiss J (2019) Antibiotic pollution in surface fresh waters: occurrence and effects. Sci Total Environ 664:793–804CrossRefGoogle Scholar
  15. 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 60:157–164CrossRefGoogle Scholar
  16. 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 56:143–150CrossRefGoogle Scholar
  17. 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 25:6122–6134CrossRefGoogle Scholar
  18. 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 12Google Scholar
  19. 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 654:324–337CrossRefGoogle Scholar
  20. Fournier D, Luft FC, Bader M, Ganten D, Andrade-Navarro MA (2012) Emergence and evolution of the renin-angiotensin-aldosterone system. J Mol Med 90:495–508CrossRefGoogle Scholar
  21. 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 11:830–838CrossRefGoogle Scholar
  22. 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 27:783–789CrossRefGoogle Scholar
  23. 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 StudiesGoogle Scholar
  24. 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 42:5807–5813CrossRefGoogle Scholar
  25. 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 129:320–332CrossRefGoogle Scholar
  26. Gutierrez JB (2001) Fundamentos de ciencia toxicológica. Ediciones Díaz de Santos, Madrid ALdCSGoogle Scholar
  27. Hayes AW, Kruger CL (2014) Principles and methods of toxicology. CRC Press, Boca RatonCrossRefGoogle Scholar
  28. 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.Google Scholar
  29. Ioele G, De Luca M, Ragno G (2016) Acute toxicity of antibiotics in surface waters by bioluminescence test. Curr Pharm Anal 12:220–226CrossRefGoogle Scholar
  30. 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 182:109429CrossRefGoogle Scholar
  31. 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 97:1167–1174CrossRefGoogle Scholar
  32. 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 35:3448–3456CrossRefGoogle Scholar
  33. Johansen MN (2012) Microalgae: biotechnology, microbiology and energy. Nova Science Publishers, New YorkGoogle Scholar
  34. 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 172:210–215CrossRefGoogle Scholar
  35. 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 64:650–660CrossRefGoogle Scholar
  36. Kümmerer K (2008) Pharmaceuticals in the environment : sources, fate. Springer, Effects and RisksCrossRefGoogle Scholar
  37. 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 568:208–215CrossRefGoogle Scholar
  38. Li M, Wei DB, Du YG (2014) Acute toxicity evaluation for quinolone antibiotics and their chlorination disinfection processes. J Environ Sci-China 26:1837–1842CrossRefGoogle Scholar
  39. 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 16:314–322Google Scholar
  40. Lichtenthaler HK (1987) Chlorophylls and carotenoids-pigments of photosynthetic biomembranes. Method Enzymol 148:350–382CrossRefGoogle Scholar
  41. 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 30:47–60CrossRefGoogle Scholar
  42. 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 23:1558–1563CrossRefGoogle Scholar
  43. 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 172:232–239CrossRefGoogle Scholar
  44. 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 690:1068–1088CrossRefGoogle Scholar
  45. McCormick PV, Cairns J (1994) Algae as indicators of environmental change. J Appl Phycol 6:509–526CrossRefGoogle Scholar
  46. 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 85:447–451CrossRefGoogle Scholar
  47. Melis A, Harvey GW (1981) Regulation of photosystem stoichiometry, chlorophyll A and chlorophyll B content and relation to chloroplast ultrastructure. Biochim Biophys Acta 637:138–145CrossRefGoogle Scholar
  48. 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 164:114953CrossRefGoogle Scholar
  49. 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 101:266–275CrossRefGoogle Scholar
  50. Nie X, Gu J, Lu J, Pan W, Yang Y (2009) Effects of norfloxacin and butylated hydroxyanisole on the freshwater microalga Scenedesmus obliquus. Ecotoxicology 18:677–684CrossRefGoogle Scholar
  51. OECD 201 Guideline for testing of chemicals (1984) Alga, Growth Inhibition TestGoogle Scholar
  52. OECD 202 Guideline for testing of chemicals (1984) Daphnia sp, Acute Inmobilisation test and Reproduction testGoogle Scholar
  53. Onorati F, Mecozzi M (2004) Effects of two diluents in the Microtox (R) toxicity bioassay with marine sediments. Chemosphere 54:679–687CrossRefGoogle Scholar
  54. Park S, Choi K (2008) Hazard assessment of commonly used agricultural antibiotics on aquatic ecosystems. Ecotoxicology 17:526–538CrossRefGoogle Scholar
  55. Passino DRM, Smith SB (1987) Acute bioassays and hazard evaluation of representative contaminants detected in great-lakes fish. Environ Toxicol Chem 6:901–907CrossRefGoogle Scholar
  56. 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 69:7371–7376CrossRefGoogle Scholar
  57. Rivetti C et al (2015) Transcriptomic, biochemical and individual markers in transplanted Daphnia magna to characterize impacts in the field. Sci Total Environ 503:200–212CrossRefGoogle Scholar
  58. 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 541:1625–1637CrossRefGoogle Scholar
  59. 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 5:229–243CrossRefGoogle Scholar
  60. 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 26:24121–24131CrossRefGoogle Scholar
  61. 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 33:142–154CrossRefGoogle Scholar
  62. 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 232:424–429CrossRefGoogle Scholar
  63. 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 17:412–419CrossRefGoogle Scholar
  64. 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 103:723–728CrossRefGoogle Scholar
  65. 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 40:17–26CrossRefGoogle Scholar
  66. 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 bacteriaGoogle Scholar
  67. 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.CrossRefGoogle Scholar
  68. 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 654:129–134CrossRefGoogle Scholar
  69. 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 110:425–430CrossRefGoogle Scholar
  70. Zhang YG, Guo J, Yao TM, Zhang YL, Zhou XF, Chu HQ (2019a) The influence of four pharmaceuticals on Chlorellapyrenoidosa culture. Sci Rep 9Google Scholar
  71. 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 38:575–584CrossRefGoogle Scholar
  72. 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 128:1–10CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Universidad San JorgeVillanueva de GállegoSpain
  2. 2.Dipartimento di scienze chimeche biologiche farmaceutiche ed ambientaliUniversità degli studi di MessinaMessinaItaly

Personalised recommendations