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Biodegradability and ecotoxicitiy of tramadol, ranitidine, and their photoderivatives in the aquatic environment

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This study was designed to assess the fate and the overall potential impacts of the widely prescribed drugs ranitidine and tramadol after their introduction into the aquatic environment.


The probability to detect these two drugs in the aquatic environment was studied by analyzing their abiotic and biotic degradation properties. For this purpose, samples were irradiated with different light sources, and three widely used biodegradability tests from the OECD series, the closed bottle test (OECD 301 D), the manometric respirometry test (OECD 301 F) and the Zahn–Wellens test (OECD 302 B), were conducted. The ecotoxicity of the photolytically formed transformation products was assessed by performing the bacterial growth inhibition test (EN ISO 10712). Furthermore, quantitative structure–activity relationship analysis and a risk analysis based on the calculation of the predicted environmental concentrations have also been conducted to assess the environmental risk potential of the transformation products. The possible formation of stable products by microbial or photolytical transformation has been investigated with DOC and LC-MS analytics.


In the present study, neither ranitidine, nor tramadol, nor their photoderivatives were found to be readily or inherently biodegradable according to test guidelines. The photolytic transformation was faster under a UV lamp compared to the reaction under an Xe lamp with a spectrum that mimics sunlight. No chronic toxicity against bacteria was found for ranitidine or its photolytic decomposition products, but a low toxicity was detected for the resulting mixture of the photolytic transformation products of tramadol.


The study demonstrates that transformation products may have a higher environmental risk potential than the respective parent compounds.

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  1. Andersen H, Siegrist H, Halling-Sørensen B, Ternes TA (2003) Fate of estrogens in a municipal sewage treatment plant. Environ Sci Technol 37:4021–4026. doi:10.1021/es026192a

  2. Carucci A, Cappai G, Piredda M (2006) Biodegradability and toxicity of pharmaceuticals in biological wastewater treatment plants. J Environ Sci Health A 41:1831–1842. doi:10.1080/10934520600779000

  3. Castiglioni S, Bagnati R, Fanelli R, Pomati F, Calamari D, Zuccato E (2006) Removal of pharmaceuticals in sewage treatment plants in Italy. Environ Sci Technol 40:357–363. doi:10.1021/es050991m

  4. Conley JM, Symes SJ, Schorr MS, Richards SM (2008) Spatial and temporal analysis of pharmaceutical concentrations in the upper Tennessee River basin. Chemosphere 73:1178–1187. doi:10.1016/j.chemosphere.2008.07.062

  5. DIN EN ISO 10712 : (1995) Pseudomonas putida Wachstumshemmtest (1981). In: Wasserchemische Gesellschaft-GDCh (Hg.): Deutsche Einheitsverfahren zur Wasser-, Abwasser- und Schlamm-Untersuchung, Band VIII, L8. 79, delievert 2010, Wiley-Vch Verlag Gmbh (in German)

  6. EMEA (European Medicines Evaluation Agency) (2006) Guideline on the environmental risk assessment of medicinal products for human use. Doc. Ref. EMEA/CHMP/SWP/4447/00, 1–12. 1-6-2006, London

  7. EPA (2007) Ecological structure activity relationship. http://www.epa.gov/oppt/newchems/tools/21ecosar.htm. Accessed July 2007

  8. Fent K (2003) Ecotoxicology. Environmental chemistry, toxicology, ecology. Thieme, Stuttgart, 2nd edition (in German)

  9. Grant SM, Langtry HD, Brogden RN (1989) Ranitidine. An updated review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in peptic ulcer disease and other allied diseases. Drugs 37:801–870. doi:10.2165/00003495-198937060-00003

  10. Gunnarsson B, Wennmalm A (2008) Drug design should involve consideration of environmental risk and hazard. Lett Drug Des Discov 5:232–235. doi:10.2174/157018008784619942

  11. Halling-Sørensen B, Nors Nielsen S, Lanzky PF, Ingerslev F, Holten Lützhoft HC, Jørgensen SE (1998) Occurrence, fate and effects of pharmaceutical substances in the environment—a review. Chemosphere 36:357–393. doi:10.1016/S0045-6535(97)00354-8

  12. Heberer T, Reddersen K, Mechlinski A (2002) From municipal sewage to drinking water: fate and removal of pharmaceutical residues in the aquatic environment in urban areas. Water Sci Technol 46:81–88

  13. Hignite C, Azarnoff DL (1977) Drugs and drug metabolites as environmental contaminants: chlorophenoxyisobutyrate and salicylic acid in sewage water effluent. Life Sci 20:337–341. doi:10.1016/0024-3205(77)90329-0

  14. Isidori M, Parrella A, Pistillo P, Temussi F (2009) Effects of ranitidine and its photoderatives in the aquatic environment. Environ Int 35:821–825. doi:10.1016/j.envint.2008.12.002

  15. Johnson AC, Jürgens MD, Williams RJ, Kümmerer K, Kortenkamp A, Sumpter JP (2008) Do cytotoxic chemotherapy drugs discharged into rivers pose a risk to the environment and human health? An overview and UK case study. J Hydrol 348:167–175. doi:10.1016/j.jhydrol.2007.09.054

  16. Kasprzyk-Hordern B, Dinsdale RM, Guwy AJ (2008) The occurrence of pharmaceuticals, personal care products, endocrine disruptors and illicit drugs in surface water in South Wales, UK. Water Res 42:3498–3518. doi:10.1016/j.watres.2008.04.026

  17. Kümmerer K (2007) Sustainable from the very beginning: rational design of molecules by life cycle engineering as an important approach for green pharmacy and green chemistry. Green Chem 9:899–907. doi:10.1039/b618298b

  18. Kümmerer K, Keil F, Hempel M, Schaefer HC (2009) Sustainable pharmacy. Umweltwiss Schadst-Forsch 21:115–117. doi:10.1007/s12302-008-0029-x

  19. Latch DE, Stender BL, McNeill K, Packer JL, Arnold WA (2003) Photochemical fate of pharmaceuticals in the environment: cimetidine and ranitidine. Environ Sci Technol 37:3342–3350. doi:10.1021/es0340782

  20. Li Q, Wang R (2006) Simultaneous analysis of tramadol, metoprolol and their metabolites in human plasma and urine by high performance liquid chromatography. Chinese Med J-Peking 119:2013–2017

  21. Lüllmann H, Mohr K, Wehling M (2003) Pharmakologie und Toxikologie, Arzneimittelwirkungen verstehen–Medikamente gezielt einsetzen. Georg Thieme Verlag, Stuttgart

  22. Nyholm N, Kristensen P (1992) Screening methods for assessment of biodegradability of chemicals in seawater—results from a ring test. Ecotoxicol Environ Safe 23:161–172. doi:10.1016/0147-6513(92)90056-9

  23. OECD (1993) Introduction to the OECD guidelines for testing of chemicals section 3. Part 1: principles and strategies related to the testing of degradation of organic chemicals. Organisation of Economic Cooperation and Development, Paris

  24. OECD (1992a) Test guideline 301D: ready biodegradability—closed bottle test. [TG 301D]. Organisation of Economic Cooperation and Development, Paris

  25. OECD (1992b) Test guideline 301F: ready biodegradability—manometric repirometry test. [TG 301F]. Organisation of Economic Cooperation and Development, Paris

  26. OECD (1992c) Test guideline 302 B: inherent biodegradability—Zahn-Wellens/EMPA. [TG 302B]. Organisation of Economic Cooperation and Development, Paris

  27. Paar WD, Poche S, Gerloff J, Dengler HJ (1997) Polymorphic CYP2D6 mediates O-demethylation of the opioid analgesic tramadol. Eur J Pharmacol 53:235–239. doi:10.1007/s002280050368

  28. Radjenovic J, Petrovic M, Barcelo D (2007) Analysis of pharmaceuticals in wastewater and removal using a membrane bioreactor. Anal Bioanal Chem 387:1365–1377. doi:10.1007/s00216-006-0883-6

  29. Red list (2010) Information on pharmaceuticals for doctors and pharmacists. http://www.roteliste.de/. Accessed 26 June 2010 (in German)

  30. Sanchez P, Tarazona JV (2002) Development of a multispecies system for testing reproductive effects on aquatic invertebrates. Experience with Daphnia magna, Chironomus prasinus and Lymnaea peregra. Aquat Toxicol 60:249–256. doi:10.1016/S0166-445X(02)00014-0

  31. Schulte-Oehlmann U, Oehlmann J, Puettmann W (2007) Human active pharmaceutical compounds in the environment: loads, detection and the trial for an inventory. UWSF–Z Umweltchem Ökotox 19:168–179. doi:10.1065/uwsf2007.07.202, in German

  32. Schwabe U, Paffrath D (2008) Arzneiverordnungs—report 2008. Springer, Heidelberg

  33. TGD (2003) Technical guidance document 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. European Commission, Brussels

  34. Webb S (2001) A data-based perspective on the environmental risk assessment of human pharmaceuticals I—collation of available ecotoxicity data and II—aquatic rids characterisation. In: Kümmerer K (ed) Pharmaceuticals in the environment sources, fate, effects and risks, 1st edn. Springer, Heidelberg, pp 175–230

  35. WHO (2010) Collaborating Centre for Drug Statistics Methodology ATC/DDD Index, 2010. http://www.whocc.no/atcddd. Accessed November 2010

  36. Zuccato E, Castiglioni S, Fanelli R, Reitano G, Bagnati R, Chiabrando C, Pomati F, Rossetti C, Calamari D (2006) Pharmaceuticals in the environment in Italy: causes, occurrence, effects and control. Environ Sci Pollut Res 13:15–21. doi:10.1065/espr2006.01.004

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The authors wish to thank the German Environment Foundation (DBU) for their excellent assistance and their financial support.

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Correspondence to Klaus Kümmerer.

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Responsible editor: Philippe Garrigues

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Bergheim, M., Gieré, R. & Kümmerer, K. Biodegradability and ecotoxicitiy of tramadol, ranitidine, and their photoderivatives in the aquatic environment. Environ Sci Pollut Res 19, 72–85 (2012). https://doi.org/10.1007/s11356-011-0536-y

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  • Aquatic environment
  • Degradation
  • Irradiation
  • Transformation
  • Ecotoxicology
  • Ranitidine
  • Tramadol