Environmental Science and Pollution Research

, Volume 26, Issue 5, pp 4224–4233 | Cite as

Toxicological study of the degradation products of antineoplastic agent etoposide in commercial formulation treated by heterogeneous photocatalysis using SrSnO3

  • Idio Alves de Sousa FilhoEmail author
  • Tatiane Martins Lobo
  • Cesar Koppe Grisolia
  • Ingrid Távora Weber
  • Marly Eiko Osugi
Advanced Oxidation Technologies: State-of-the-Art in Ibero-American Countries


Etoposide is an antineoplastic agent used for treating lung cancer, testicular cancer, breast cancer, pediatric cancers, and lymphomas. It is a pollutant due to its mutagenic and carcinogenic potential. Disposal of waste from this drug is still insufficiently safe, and there is no appropriate waste treatment. Therefore, it is important to use advanced oxidative processes (AOPs) for the treatment and disposal of medicines like this. The use of strontium stannate (SrSnO3) as a catalyst in heterogeneous photocatalysis reactions has emerged as an alternative for the removal of organic pollutants. In our study, SrSnO3 was synthesized by the combustion method and characterized by X-ray diffraction (XRD), Raman, UV-Vis, and scanning electron microscopy (SEM) techniques, obtaining a surface area of 3.28 m2 g−1 with cubic and well-organized crystallinity and a band gap of 4.06 eV. The experimental conditions optimized for degradation of an etoposide solution (0.4 mg L−1) were pH 5 and catalyst concentration of 1 g L−1. The results showed that the degradation processes using SrSnO3 combined with H2O2 (0.338 mol L−1) obtained total organic carbon removal from the etoposide solution, 97.98% (± 4.03 × 10−3), compared with TiO2, which obtained a mineralization rate of 72.41% (± 6.95 × 10–3). After photodegradation, the degraded solution showed no toxicity to zebrafish embryos through embryotoxicity test (OECD, 236), and no genotoxicity using comet assay and micronucleus test.


AOPs Waste treatment Antineoplastic SrSnO3 Micronucleus test Comet assay 



The authors wish to thank the Brazilian funding agencies MCTI/CNPq (no. 483682 / 2013-6) and CAPES for their financial support, the Institute of Chemistry of the University of Brasília and the Toxicologic Genetics Laboratory (G-TOX) of the Institute of Biological Sciences of the University of Brasília.


  1. Alves MCF, Marinho RMM, Casali GP, Siu-Li M, Députier S, Guilloux-Viry M, Souza AG, Longo E, Weber IT, Santos IMG, Bouquet V (2013) Influence of the network modifier on the characteristics of MSnO3 (M = Sr and Ca) thin films synthesized by chemical solution deposition. J Solid State Chem 199:34–41CrossRefGoogle Scholar
  2. Araceli G-A, Broséus R, Vincent S, Barbeau B, Prévost M, Sauvé S (2010) Oxidation kinetics of cyclophosphamide and methotrexate by ozone in drinking water. Chemosphere 79:1056–1063CrossRefGoogle Scholar
  3. Boczkaj G, Fernandes A (2017) Wastewater treatment by means of advanced oxidation processes at basic pH conditions: a review. Chem Eng J 320:608–633CrossRefGoogle Scholar
  4. Buerge IJ, Buser H-R, Poiger T, Muller MD (2006) Occurrence and fate of the cytostatic drugs cyclophosphamide and ifosfamide in wastewater and surface waters. Environ Sci Technol 40:7242–7250CrossRefGoogle Scholar
  5. Cabeza Y, Candela L, Ronen D, Teijon G (2012) Monitoring the occurrence of emerging contaminants in treated wastewater and groundwater between 2008 and 2010. The Baix Llobregat (Barcelona, Spain). J Hazard Mater 239:32–39CrossRefGoogle Scholar
  6. Cavalcante RP, Sandim LR, Bogo D, Barbosa AMJ, Osugi ME, Blanco M, Oliveira SC, Matos MFC, Junior AM, Ferreira VS (2013) Application of Fenton, photo-Fenton, solar photo-Fenton, and UV/H2O2 to degradation of the antineoplastic agent mitoxantrone and toxicological evalution. Environ Sci Pollut Res 20:2352–2361CrossRefGoogle Scholar
  7. Chen D, Ye J (2007) SrSnO3 nanostructure: synthesis, characterization, and photocatalytic properties. Chem Mater 19:4585–4591CrossRefGoogle Scholar
  8. Crittenden JC, Hu S, Hand DW, Green SA (1999) A kinetic model for H2O2/UV process in a completely mixed batch reactor. Water Res 33:235–2328CrossRefGoogle Scholar
  9. Fenech M, Chang WP, Kirsch-Volders M, Holland N, Bonassi S, Zeiger E (2003) HUMN project: detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures. Mutat Res 534:65–75CrossRefGoogle Scholar
  10. Gajski G, Gerić M, Žegura B, Novak M, Nunić J, Bajrektarević D, Garaj-Vrhovac V, Filipič M (2016) Genotoxic potential of selected cytostatic drugs in human and zebrafish cells. Environ Sci Pollut Res 23:14739–14750CrossRefGoogle Scholar
  11. Hadjarab B, Bouguelia A, Trari M (2007) Synthesis, physical and photo electrochemical characterization of La-doped SrSnO3. J Phys Chem Solids 68:1491–1499CrossRefGoogle Scholar
  12. Hayashi M, Kodama Y, Awogi T, Suzuki T, Asita AO, Sofuni T (1992) The micronucleus assay using peripheral blood reticulocytes from mitomycin C-and cyclophosphamide-treated rats. Mutat Res 278:209–213CrossRefGoogle Scholar
  13. Hernando M, Mezcua M, Fernández-Alba AR, Barceló D (2006) Environmental risk assessment of pharmaceutical residues in wastewater effluents, surface waters and sediments. Talanta 69:334–342CrossRefGoogle Scholar
  14. Hodjati S, Vaezzadeh K, Petit C, Pitchon V, Kiennemann A (2000) Absorption/desorption of NOx process on perovskites: performances to remove NOx from a lean exhaust gas. Appl Catal B Environ 26:5–16CrossRefGoogle Scholar
  15. Junploy P, Thongtem S, Thongtem T (2013) Photoabsorption and photocatalysis of SrSnO3 produced by a cyclic microwave radiation. Superlattice Microst 57:1–10CrossRefGoogle Scholar
  16. Konstantinou IK, Albanis AT (2004) TiO2-assisted photocatalytic degradation of azo dyes in aqueous solution: kinetic and mechanistic investigations: a review. Appl Catal B Environ 49:1–14CrossRefGoogle Scholar
  17. Kosmehl T, Hallare AV, Braunbeack T, Hollert H (2008) DNA damage induced by genotoxicants in zebrafish (Danio rerio) embryos after contact exposure to freeze-dried sediment and sediment extracts from Laguna Lake (The Philippines) as measured by the comet assay. Mutat Res 650:1–14CrossRefGoogle Scholar
  18. Lee CW, Kim DW, Cho IS, Park S, Shin SS, Seo SW, Hong KS (2012) Simple synthesis and characterization of SrSnO3 nanoparticles with enhanced photocatalytic activitiy. Int J Hydrog Energy 37:10557–10563CrossRefGoogle Scholar
  19. Liu N, Zhang L, Xue Y, Lv J, Yu Q, Yuan X (2017) Nitrogen-doped carbon material as a catalyst for the degradation of direct red23 based on persulfate oxidation. Sep Purif Technol 184:213–219CrossRefGoogle Scholar
  20. Lobo TM, Lebullenger R, Bouquet V, Guilloux-Viy M, Santos IM, Weber IT (2015) SrSnO3:N – nitridation and evaluation of photocatalytic activity. J Alloys Compd 649:1–15CrossRefGoogle Scholar
  21. Lucena GL, Souza JJN, Maia AS, Soledade LEB, Longo E, Souza AG, Santos IMG (2013) New methodology for faster synthesis of SrSnO3 by the modified Pechini method. Cerâmica 59:249–253CrossRefGoogle Scholar
  22. Lutterbeck CA, Kern DI, Machado LE, Kummer K (2015) Evaluation of the toxic effects of four anti-cancer drugs in plant bioassays and its potency for screening in the context of waste water reuse for irrigation. Chemosphere 135:403–410CrossRefGoogle Scholar
  23. Ma Y, Li M, Wu M, Liu X (2015) Occurrences and regional distributions of 20 antibiotics in water bodies during groundwater recharge. Sci Total Environ 518:489–506Google Scholar
  24. McEneff G, Schmidt W, Quinn B (2014) Pharmaceuticals in the aquatic environment: a short summary of current knowledge and the potential impacts on aquatic biota and humans. Environmental Protection Agency, Wexford, IrelandGoogle Scholar
  25. National Cancer Institute (INCA) (2018) Brazil: Ministério da Saúde. INC; cl 996–2018 Availab from: Accessed on February 02, 2018 (in Portuguese)
  26. Nogueira RFP, Oliveira MC, Paterlini WC (2005) Simple and fast spectrophotometric determination of H2O2 in photo-Fenton reactions using metavanadate. Talanta 66:86–91CrossRefGoogle Scholar
  27. Nussbaumer S, Bonnabry P, Veuthey JL, Fleury-Souverain S (2011) Analysis of anticancer drugs: a review. Talanta 85:2265–2289CrossRefGoogle Scholar
  28. Ocampo-Pérez R, Sanchez-Polo M, Rivera-Utrillia J, Leyva-Ramos R (2010) Degradation of antineoplastic cytrabine inaqueous phase by advanced oxidation processes based on ultraviolet radiation. Chem Eng J 165:581–588CrossRefGoogle Scholar
  29. OECD (2013) Test No. 236: Fish embryo acute toxicity (FET) test. Oecd Publishing, Paris (OECD Guidelines for the Testing of Chemicals, Section 2)CrossRefGoogle Scholar
  30. Oller I, Malato S, Sánchez-Pérez J (2011) A combination of advanced oxidation processes and biological trataments for wastwater decontamination—a review. Sci Total Environ 409:4141–4166CrossRefGoogle Scholar
  31. Peña M, Fierro J (2001) Chemical structures and performance of perovskitas oxide. Chem Rev 101:1981–2017CrossRefGoogle Scholar
  32. Sales HS, Bouquet V, Députier S, Olivier S, Gouttefangeas F, Guilloux-Viry M, Santos IMG (2014) Sr1-xBaxSnO3 system applied in the photocatalytic discoloration of a an azo-dye. Solid State Sci 28:67–73CrossRefGoogle Scholar
  33. Solano A, da Silva G, Fialho S (2012) Development and validation of a high performance liquid chromatographic method for determination of etoposide in biodegradable polymeric implants. Quím Nova 35:1239–1243CrossRefGoogle Scholar
  34. Stahelin HF, Vin AW (1991) The chemical and biological route from podophyllotoxin glucoside to etoposide: Ninth Cain Memorial Award Lecture. Cancer Res 51:5–15Google Scholar
  35. Tauc J (1966) The optical properties of solids. Academic Press, New YorkGoogle Scholar
  36. Tice RR, Agurell E, Anderson D, Burlinson B, Hartmann A, Kobayashi H, Sasaki YF (2000) Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 35:206–221CrossRefGoogle Scholar
  37. Verlicchi P, Galletti A, Petrovic M, Baceló D (2010) Hospital effluents as a source of emerging pollutants: An overview of micropollutants and sustainable treatment options. J Hydrol 389:416–428CrossRefGoogle Scholar
  38. Vogna D, Marotta R, Andreozzi R, Napolitano A, d’Ischia M (2004) Kinetic and chemical assessment of the UV/H2O2 treatment of antiepileptic drug carbamazepine. Chemosphere 54:497–505CrossRefGoogle Scholar
  39. Wang S, Zhou G, Zhang A, Yang Z (2007) Systematic investigations into SrSnO3 nanocrystals (I) synthesis by using combustion and coprecipitation methods. J Alloys Compd 432:265–268CrossRefGoogle Scholar
  40. Wu JJ, Wu CC, Ma HW, Chang CC (2004) Treatment of landfill leachate by ozone-based advanced oxidation processes. Chemosphere 54:997–1003CrossRefGoogle Scholar
  41. Yuan Y, Li XJZ, Yu T, Zou Z (2007) Large impact of strontium substitution on photocatalytic water splitting activity of BaSnO3. Appl Phys Lett 91:094107CrossRefGoogle Scholar
  42. Yurdakal S, Loddo V, Augugliaro V, Berber H, Palmisano G, Palmisano L (2007) Photodegradation of pharmaceutical drugs in aqueous TiO2: Mechanism and kinetics. Catal Today 129:9–15CrossRefGoogle Scholar
  43. Zeng MC, Huang D, Lai C, Xu P, Zhang C, Liu Y (2016) Hydroxyl radicals based advanced oxidation processes (AOPs) for remediation of soils contaminated with organic compounds: a review. Chem Eng J 284:582–598CrossRefGoogle Scholar
  44. Zhang W, Tang J, Ye J (2006) Photoluminescence and photocatalytic properties of SrSnO3 perovskite. Chem Phys Lett 418:174–178CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Instituto de QuímicaUniversidade de Brasília-UnBBrasíliaBrazil
  2. 2.Instituto de Ciências Biologia, Departamento de Genética e MorfologiaUniversidade de Brasília-UnBBrasíliaBrazil
  3. 3.Unesp, Instituto Nacional de Tecnologias Alternativas para Detecção, Avaliação Toxicológica e Remoção de Micropoluentes e Radioativos (INCT-DATREM), Instituto de QuímicaAraraquaraBrazil

Personalised recommendations