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Effects of Pharmaceuticals on Aquatic Invertebrates. Part II: The Antidepressant Drug Fluoxetine

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Abstract

Fluoxetine, a selective serotonin reuptake inhibitor antidepressant and high-prescription-volume drug, is excreted unchanged or as a glucuronide from the human organism. Little is known about its fate in sewage treatment plants. Effects of fluoxetine on life-cycle parameters of the midge Chironomus riparius, especially development (mean emergence time), emergence, sex ratio, and fecundity, were assessed, as well as effects on reproduction of the oligochaete Lumbriculus variegatus and of the freshwater mudsnail Potamopyrgus antipodarum. Due to the moderate lipophilic properties of the compound with a log P OW of 4.05, C. riparius and L. variegatus were exposed to fluoxetine via spiked artificial sediment at a nominal concentration range between 0.15 and 5.86 mg/kg (dry weight). Additionally, a test was performed exposing P. antipodarum via water in a nominal concentration range between 0.64 and 400 μg/L. As endpoints, emergence rate and timing, sex ratio, clutch numbers and clutch size of the midges, the number of worms in the oligochaete test, as well as the number of embryos in the snail test were monitored. For C. riparius, no clear substance-related effects were observed; for L. variegatus, the results indicated a slight increase in reproduction, which was statistically significant at nominal fluoxetine concentrations of 0.94 and 2.34 mg/kg. In P. antipodarum, the antidepressant reduced reproduction significantly. No observed effect concentration (NOEC) and 10% effect concentration (EC10) were determined to be 0.47 and 0.81 μg/L, respectively, based on measured fluoxetine concentrations in water. These low values indicate that P. antipodarum and possibly other aquatic mollusks are sensitive to fluoxetine and that the drug might pose a risk to gastropod populations in the field.

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References

  • ASTM (1995) E 1706-95a Standard test methods for measuring the toxicity of sediment-associated contaminations with freshwater invertebrates. American Society for Testing and Materials, West Conshohocken, PA

  • Avila C, Tamse CT, Kuzirian AM (1996) Induction of metamorphosis in Hermissenda crassicornis larvae (Mollusca: Nudibranchia) by GABA, choline and serotonin. Invert Rep Dev 29:127–141

    CAS  Google Scholar 

  • Barondes SH (1994) Thinking about Prozac. Science 263:1102–1103

    Article  CAS  Google Scholar 

  • Brooks BW, Turner PK, Stanley JK, Weston JJ, Glidewell EA, Foran CM, Slattery M, La Point TW, Huggett DB (2003) Waterborne and sediment toxicity of fluoxetine to select organisms. Chemosphere 52:135–142

    Article  CAS  Google Scholar 

  • Brust K, Licht O, Hultsch V, Jungmann D, Nagel R (2001) Effects of terbutryn on aufwuchs and Lumbriculus variegatus in artificial indoor streams. Environ Toxicol Chem 20:2000–2007

    Article  CAS  Google Scholar 

  • Duft M, Schulte-Oehlmann U, Tillmann M, Markert B, Oehlmann J (2003a) Toxicity of triphenyltin and tributyltin to the freshwater mudsnail Potamopyrgus antipodarum in a new sediment biotest. Environ Toxicol Chem 22:145–152

    Article  CAS  Google Scholar 

  • Duft M, Schulte-Oehlmann U, Weltje L, Tillmann M, Oehlmann J (2003b) Stimulated embryo production as a parameter of estrogenic exposure via sediments in the freshwater mudsnail Potamopyrgus antipodarum. Aquat Toxicol 64:437–449

    Article  CAS  Google Scholar 

  • Egeler P, Römbke J, Meller M, Knacker T, Franke C, Studinger G, Nagel R (1997) Bioaccumulation of lindane and hexachlorobenzene to tubificid sludgeworms (Oligochaeta) under standardised laboratory conditions. Chemosphere 35:835–852

    Article  CAS  Google Scholar 

  • Egeler P, Meller M, Schallnass H, Gilberg D, in cooperation with Karaoglan B, Nagel R (2005) Validation of a sediment toxicity test with the endobenthic aquatic oligochaete Lumbriculus variegatus by an international ring test. Report FKZ 202 67 429, Umweltbundesamt, Berlin, Germany

  • EMEA (2005) Guideline on the environmental risk assessment of medicinal products for human use. European Medicines Agency, London

    Google Scholar 

  • EU (2003) Technical Guidance Document on Risk Assessment in support of Commission Directive 93/67/EEC on Risk Assessment for new notified substances, Commission Regulation (EC) No. 1488/94 on Risk Assessment for existing substances and Directive 98/8/EC of the European Parliament and of the Council concerning the placing of biocidal products on the market, Parts I, II and IV. European Communities, 2003. EUR 20418 EN/1

  • Fiedler HJ, Rösler HJ (1993) Spurenelemente in der Umwelt. Gustav Fischer Verlag, Stuttgart

    Google Scholar 

  • Fong PP (1998) Zebra mussel spawning is induced in low concentrations of putative serotonin reuptake inhibitors. Biol Bull 194:143–149

    CAS  Google Scholar 

  • Fong PP, Wall DM, Ram JL (1993) Characterization of serotonin receptors in the regulation of spawning in the zebra mussel Dreissena polymorpha (Pallas). J Exp Zool 267:475–482

    Article  CAS  Google Scholar 

  • Fong PP, Duncan J, Ram JL (1994) Inhibition and sex specific induction of spawning by serotonergic ligands in the zebra mussel Dreissena polymorpha (Pallas). Experientia 50:506–509

    Article  CAS  Google Scholar 

  • Fong PP, Deguchi R, Kyozuka K (1996) Serotonergic ligands induce spawning but not oocyte maturation in the bivalve Mactra chinensis from Central Japan. Biol Bull 191:27–32

    Google Scholar 

  • Fong PP, Huminski PT, D’Urso LM (1998) Induction and potentiation of parturition in fingernail clams (Sphaerium striatinum) by selective serotonin re-uptake inhibitors (SSRIs). J Exp Zool 280:260–264

    Article  CAS  Google Scholar 

  • Hartke K, Mutschler E (eds) (1993) Deutsches Arzneibuch DAB 10—Kommentar, 10th ed. Deutscher Apotheker-Verlag, Stuttgart, Vols II and III, 3rd Suppl

  • Hecker V (2004) Effekte von Arzneimittelrückständen in der aquatischen Umwelt. Diploma thesis, Department of Biosciences, Johann Wolfgang Goethe University, Frankfurt

  • Hessling R, Müller MC, Westheide W (1999) CLSM analysis of serotonin-immunoreactive neurons in the central nervous system of Nais variabilis, Slavina appendiculata and Stylaria lacustris (Oligochaeta: Naididae). Hydrobiologia 406:223–233

    Article  Google Scholar 

  • Hirai S, Kishimoto T, Kadam AL, Kanatani H, Koide SS (1988) Induction of spawning and oocyte maturation by 5-hydroxytryptamine in the surf clam. J Exp Zool 245:318–321

    Article  CAS  Google Scholar 

  • Honkoop PJC, Luttikhuizen PC, Piersma T (1999) Experimentally extending the spawning season of a marine bivalve using temperature change and fluoxetine as synergistic triggers. Mar Ecol Prog Ser 180:297–300

    Google Scholar 

  • Jobling S, Casey D, Rodgers-Gray T, Oehlmann J, Schulte-Oehlmann U, Pawlowski S, Braunbeck T, Turner AP, Tyler CR (2004) Comparative responses of molluscs and fish to environmental estrogens and an estrogenic effluent. Aquat Toxicol 66:207–222

    Article  CAS  Google Scholar 

  • Kolpin DW, Furlong ET, Meyer MT, Thurman EM, Zaugg SD, Barber LB, Buxton HT (2002) Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999–2000: A national reconnaissance. Environ Sci Technol 36:1202–1211

    Article  CAS  Google Scholar 

  • Krantic S, Dube F, Quiron R, Guerrier P (1991) Pharmacology of the serotonin-induced meiosis reinitiation in Spisula solidissima oocytes. Dev Biol 146:491–498

    Article  CAS  Google Scholar 

  • Kusk KO (2003) KOK-456T2. Program manual for statistical data treatment of toxicity test results. Technical University of Denmark, Lyngby

  • Leppänen MT, Kukkonen JVK (1998) Factors affecting feeding rate, reproduction and growth of the oligochaete Lumbriculus variegatus (Müller). Hydrobiologia 377:183–194

    Article  Google Scholar 

  • Loeffler D (2003) Fate of human and veterinary pharmaceuticals in water/sediment test systems by analysis via LC-tandem MS and radio-TLC. PhD thesis, Department of Chemistry/Pharmacy, Johannes Gutenberg-University, Mainz

  • Medawar C (1994) Through the doors of perception? Nature 368:369–370

    Article  Google Scholar 

  • Metcalfe CD, Xiu-Sheng M, Koenig BG, Struger J (2003) Distribution of acidic and neutral drugs in surface waters near sewage treatment plants in the lower Great Lakes, Canada. Environ Toxicol Chem 22:2881–2889

    Article  CAS  Google Scholar 

  • Möhle E, Kempter C, Kern A, Metzger JW (1999) Untersuchungen zum Abbau von Pharmaka in kommunalen Kläranlagen mit HPLC-Electrospray-Massenspektrometrie. Acta Hydrochim Hydrobiol 27:430–436

    Article  Google Scholar 

  • OECD (2004) OECD guidelines for the testing of chemicals. Guideline 218: Sediment-water chironomid toxicity test using spiked sediment. Organisation for Economic Co-operation and Development, Paris

    Google Scholar 

  • Oetken M, Nentwig G, Löffler D, Ternes T, Oehlmann J (2005) Effects of pharmaceuticals on aquatic invertebrates. Part I. The antiepileptic drug carbamazepine. Arch Environ Contam Toxicol 49:353–361

    Article  CAS  Google Scholar 

  • Olfson M, Marcus SC, Pincus HA, Zito JM, Thompson JW, Zarin DA (1998) Antidepressant prescribing practices of outpatient psychiatrists. Arch Gen Psychol 55:310–316

    Article  CAS  Google Scholar 

  • Phipps GL, Ankley GT, Benoit DA, Mattson VR (1993) Use of the aquatic oligochaete Lumbriculus variegatus for assessing the toxicity and bioaccumulation of sediment-associated contaminants. Environ Toxicol Chem 12:269–279

    CAS  Google Scholar 

  • Ram JL, Crawford GW, Walker JU, Mojares JJ, Patel N, Fong PP, Kyozuka K (1993) Spawning in the zebra mussel (Dreissena polymorpha): Activation by internal or external application of serotonin. J Exp Zool 265:587–598

    Article  CAS  Google Scholar 

  • Sattelberger R (1999) Arzneimittelrückstände in der Umwelt. Bestandsaufnahme und Problemdarstellung. Report R-162, Federal Environmental Agency, Vienna

  • Schulte-Oehlmann U (1997) Fortpflanzungsstörungen bei Süß- und Brackwasserschnecken: Einfluß der Umweltchemikalie Tributylzinn. Wissenschaft und Technik Verlag, Berlin

    Google Scholar 

  • Schulte-Oehlmann U, Tillmann M, Casey D, Duft M, Markert B, Oehlmann J (2001) Östrogenartige Wirkungen von Bisphenol A auf Vorderkiemerschnecken (Mollusca: Gastropoda: Prosobranchia). UWSF—Z Umweltchem Ökotox 13:319–333

    CAS  Google Scholar 

  • Schwabe U, Paffrath D (2004): Arzneiverordnungs-Report: Aktuelle Daten, Kosten, Trends und Kommentare. Springer-Verlag, Berlin

    Google Scholar 

  • Sebastine IM, Wakeman RJ (2003) Consumption and environmental hazards of pharmaceutical substances in the UK. Process Safety Environ 81:229–235

    Article  CAS  Google Scholar 

  • Sprague JB, Fogels J (1977) Watch the y in bioassay. Environmental Protection Service technical report No. EPS-5-AR-77-1, Halifax, Nova Scotia, Canada, pp 107–118

  • Ternes TA (1998) Occurrence of drugs in German sewage treatment plants and rivers. Water Res 32:3245–3260

    Article  CAS  Google Scholar 

  • Ternes TA (2000) Pharmaceuticals and metabolites as contaminants of the aquatic environment: An overview. In: Keith LH, Needham LL, Jones-Lepp TL (eds) Issues in the analysis of environmental endocrine disruptors. Proceedings Volume ACS Symposium 40. American Chemcal Society, San Francisco, pp 98–100

    Google Scholar 

  • Tixier C Singer HP, Oellers S, Müller SR (2003) Occurrence and fate of carbamazepine, clofibric acid, diclofenac, ibuprofen, ketoprofen, and naproxen in surface waters. Environ Sci Technol 37:1061–1068

    Article  CAS  Google Scholar 

  • Uhler GC, Huminski PT, Les FT, Fong PP (2000) Cilia-driven rotational behavior in gastropod (Physa elliptica) embryos induced by serotonin and putative serotonin reuptake inhibitors (SSRIs). J Exp Zool 286:414–421

    Article  CAS  Google Scholar 

  • West CW, Ankley GT (1998) A laboratory assay to assess avoidance of contaminated sediments by the freshwater oligochaete Lumbriculus varigatus. Arch Environ Contam Toxicol 35:20–24

    Article  CAS  Google Scholar 

  • Weston JJ, Huggett DB, Rimoldi J, Foran CM, Stattery M (2001) Determination of fluoxetine (Prozac™) and norfluoxetine in the aquatic environment. Annual Meeting of the Society of Environmental Toxicology and Chemistry, Baltimore, MD

  • Williams RW, Herrup K (1988) The control of neuron number. Annu Rev Neurosci 11:423–453

    Article  CAS  Google Scholar 

  • Wong DT, Bymaster FP, Engleman EA (1995) Prozac (fluoxetine, Lilly 110140), the first selective serotonin uptake inhibitor and an antidepressant drug: 20 years since its first publication. Life Sci 57:411–441

    Article  CAS  Google Scholar 

  • Young WF, Whitehouse P, Johnson I, Sorokin N (2002) Proposed predicted-no-effect-concentrations (PNECs) for natural and synthetic steroid oestrogens in surface waters. Research and Development technical report P2-T04/1. Environment Agency, Bristol, UK

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Acknowledgments

We thank Gabi Elter for excellent technical assistance, the Center of Environmental Research (ZUF) at the University Frankfurt am Main for financial support, and two anonymous reviewers for their valuable comments. Many thanks also to Karen Nelson for the linguistic revision of this manuscript.

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Correspondence to Gerrit Nentwig.

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Nentwig, G. Effects of Pharmaceuticals on Aquatic Invertebrates. Part II: The Antidepressant Drug Fluoxetine. Arch Environ Contam Toxicol 52, 163–170 (2007). https://doi.org/10.1007/s00244-005-7190-7

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