Skip to main content

Advertisement

Log in

Evaluation of the potential environmental risk from the destination of medicines: an epidemiological and toxicological study

  • Research article
  • Published:
DARU Journal of Pharmaceutical Sciences Aims and scope Submit manuscript

Abstract

Background

The high consumption of medicines by the population and their storage at home might cause an increase in the number of pharmaceutical substances that may be inappropriately discarded in the sanitary sewage, reaching an environmental aquatic. Thus, the effects of these emerging contaminants need more studies.

Objectives

To identify the profile of most medicines that are discarded by users of community pharmacy and evaluate the toxicity of the most disposed drugs.

Methods

This was a translational study. A descriptive observational study was carried out for convenience of community pharmacy users using a standardized questionnaire. Subsequently, the lethal concentration 50 (LC50) for medicine that is most frequently discarded was determined. After LC50, the embryos (n = 144) were exposed to sublethal concentrations for most discarded drug at 24, 48, and 72 h. Mortality, heartbeat, and embryo deformities were used as parameters of toxicity.

Results

Most respondents (96%) had a “home pharmacy.” The primary forms of disposal were in the common household waste, kitchen sink, and/or bathroom. The medicines that were most incorrectly discarded by the interviewees were nimesulide (17.1%), dipyrone (10.7%), and paracetamol (5.2%). LC50 of nimesulide was calculated (0.92 μgmL−1). The toxicological test revealed that embryos exposed to nimesulide showed several abnormalities, such as defects in the spinal cord, tail, yolk sac, as well as pericardial edema. Furthermore, the heartbeat decreased by 30% at a concentration of 0.4 μgmL−1 as compared with control group. The yolk sac and pericardial areas increased to >100% in all treatment groups when compared with the control group.

Conclusion

Respondents disposed medicines in an inappropriate manner primarily in household waste and in the toilet. Nimesulide was the most discarded drug according to study population. Moreover, teratogenic effects such as spinal cord defects, decreasing heartbeats, and increasing pericardial and yolk sac area in embryos were observed after exposure to nimesulide. These results show that nimesulide may promote risk to aquatic organisms and to human health if it is discarded in an unsafe manner.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Sposito JCV, Montagner CC, Casado M, Navarro-Martín L, Jut SJC, Piña B, et al. Emerging contaminants in Brazilian rivers: occurrence and effects on gene expression in zebrafish (Danio rerio) embryos. Chemosphere. 2018;209:696–704.

    Article  CAS  PubMed  Google Scholar 

  2. Silva AS, Maciel GA, Wanderley LSL, Wanderley AG. Drug use indicators in primary health care: a systematic review. Rev Panam Salud Publica. 2017;41:132–43.

    Google Scholar 

  3. Bilal M, Adeel M, Rasheed T, Zhao Y, Iqbal HMN. Emerging contaminants of high concern and their enzyme-assisted biodegradation – a review. Environ Int. 2019;124:336–53.

    Article  CAS  PubMed  Google Scholar 

  4. Rasheed T, Bilal M, Nabeel F, Adeel M, Iqbal HMN. Environmentally-related contaminants of high concern: potential sources and analytical modalities for detection, quantification, and treatment. Environ Int. 2019;122:52–66.

    Article  CAS  PubMed  Google Scholar 

  5. Lofrano G, Libralato G, Meric S, Vaiano V, Sacco O, Venditto V, Guida M, Carotenuto M. Occurrence and potential risks of emerging contaminants in water. In Visible light active structured photocatalysts for the removal of emerging contaminants. Elsevier; 2020. pp. 1–25.

  6. van der Aa NGFM, Kommer GJ, van Montfoort JE, Versteegh JFM. Demographic projections of future pharmaceutical consumption in the Netherlands. Water Sci Technol. 2011;63(4):825–31.

    Article  PubMed  Google Scholar 

  7. Bueno CS, Weber D, Oliveira KR. Home pharmacy and drug disposal in the Luiz Fogliatto neighborhood from municipality of Ijuí - RS. J Appl Basic Pharm Sci. 2009;30(2):203–10.

    Google Scholar 

  8. Rodrigues MS, Mônica F, Freitas MD, Dalbó S. Dispose of household medicines and its environmental impact: analysis of a community understanding. Braz Appl Sci Rev. 2018;2(6):1857–68.

    Google Scholar 

  9. Alvarenga LSV, Nicoletti MA. Domestic discarding of medicines and some considerations about the current environment impact. Rev Saude Publica. 2010;4(3):34–9.

    Google Scholar 

  10. Vaz KV, Freitas MM, Cirqueira JZ. Investigation about ways of discarding expired medicines. Cenarium Pharmaceutico. 2011;4(4):17–20.

    Google Scholar 

  11. Schwingel D, De Souza J, Simonetti E, Rigo MPM, Ely LS, De Castro LC, et al. Home pharmacy versus rational medicine use. Rev Caderno Pedagogico. 2015;12(3):117–30.

    Google Scholar 

  12. Ueda J, Tavernaro R, Marostega V, Pavan W. Environmental impact of drugs disposal and study of population awareness about the problem. Rev Bras Cienc Amb. 2009;5(9).

  13. Quadra GR, Silva PSA, Paranaíba JR, Josué IIP, Souza H, Costa R, et al. Investigation of medicines consumption and disposal in Brazil: a study case in a developing country. Sci Total Environ. 2019;671:505–9.

    Article  CAS  PubMed  Google Scholar 

  14. Lenhardt EH, Sólis LJB, Cintra EVCS, Botelho EHLO. Drug disposal at Grande Terceiro neighborhood, Cuiabá-MT. UNOPAR Cient Cienc Biol Saude. 2014;16(1):5–8.

    Google Scholar 

  15. Ribas JLC, Silva CA, Andrade L, Galvan GL, Cestari MM, Trindade ES, et al. Effects of anti-inflammatory drugs in primary kidney cell culture of a freshwater fish. Fish Shellfish Immunol. 2014;40(1):296–303.

    Article  CAS  PubMed  Google Scholar 

  16. Gaffney VJ, Cardoso VV, Rodrigues A, Ferreira E, Benoliel MJ, Almeida CMM. Analysis of pharmaceutical compounds in water by SPE-UPLC-ESI-MS/MS. Quim Nova. 2014;37(1):138–49.

    Article  CAS  Google Scholar 

  17. Santos LH, Araujo AN, Fachini A, Pena A, Delerue-Matos C, Montenegro MC. Ecotoxicological aspects related to the presence of pharmaceuticals in the aquatic environment. J Hazard Mater. 2010;175(1–3):45–95.

    Article  CAS  PubMed  Google Scholar 

  18. Hermoso V, Clavero M, Blanco-Garrido F, Prenda J. Assessing the ecological status in species-poor systems: a fish-based index for Mediterranean Rivers (Guadiana River, SW Spain). Ecol Indic. 2010;10(6):1152–61.

    Article  Google Scholar 

  19. Sales CF, Santos KPE, Rizzo E, Ribeiro RIMA, Santos HB, Thomé RG. Proliferation, survival and cell death in fish gills remodeling: from injury to recovery. Fish Shellfish Immunol. 2017;68:10–8.

    Article  PubMed  Google Scholar 

  20. Shi Q, Zhuang Y, Hu T, Lu C, Wang X, Huang H, et al. Developmental toxicity of triclocarban in zebrafish (Danio rerio) embryos. J Biochem Mol Toxicol. 2019;33(5):e22289.

    Article  PubMed  Google Scholar 

  21. Gomes TB, Fernandes S, Junior S, Saint’pierre TD, Correia FV, Hauser-Davis RA, et al. Sublethal psychotropic pharmaceutical effects on the model organism Danio rerio: oxidative stress and metal dishomeostasis. Ecotoxicol Environ Saf. 2019;171:781–9.

    Article  CAS  PubMed  Google Scholar 

  22. De Lima LBD, de Morais PB, de Andrade RLT, Mattos LV, Moron SE. Use of biomarkers to evaluate the ecological risk of xenobiotics associated with agriculture. Environ Pollut. 2018;237:611–24.

    Article  PubMed  Google Scholar 

  23. Guimarães R. Translational research: an interpretation. Cien Saude Coletiva. 2013;18:1731–44.

    Article  Google Scholar 

  24. Fernandes MR, Figueiredo RC, Silva LGR, Rocha RS, Baldoni AO. Storage and disposal of expired medicines in home pharmacies: emerging public health problems. Einstein (São Paulo). 2020;18:eAO5066.

    Article  Google Scholar 

  25. Population of Divinopolis City from IBGE 2019. https://cidades.ibge.gov.br/brasil/mg/divinopolis/panorama. Accessed 18 Aug 2020.

  26. Finney DJ, Stevens WL. A table for the calculation of working probits and weights in probit analysis. Biometrika. 1948;35(1–2):191–201.

    Article  CAS  PubMed  Google Scholar 

  27. Chakraborty C, Hsu CH, Wen ZH, Lin CS, Agoramoorthy G. Effect of caffeine, norfloxacin and nimesulide on heartbeat and VEGF expression of Zebrafish larvae. J Environ Biol. 2011;32(2):179–83.

    CAS  PubMed  Google Scholar 

  28. Strykowski JL, Schech JM. Effectiveness of recommended euthanasia methods in larval zebrafish (Danio rerio). J Am Assoc Lab Anim Sci. 2015;54(1):81–4.

    PubMed  Google Scholar 

  29. Organization for Economic Cooperation and Development (OECD). Test No. 236: Fish Embryo Acute Toxicity (FET) Test. In: OECD Guidelines for the Testing of Chemicals, Section 2: Biotic Effects. Paris: OECD Publishing; 2013. pp.1–22.

  30. Rawlings JM, Belanger SE, Connors KA, Carr GJ. Fish embryo tests and acute fish toxicity tests are interchangeable in the application of the threshold approach. Environ Toxicol Chem. 2019;38(3):671–81.

    Article  CAS  PubMed  Google Scholar 

  31. Rangasamy B, Hemalatha D, Shobana C, Nataraj B, Ramesh M. Developmental toxicity and biological responses of zebrafish (Danio rerio) exposed to anti-inflammatory drug ketoprofen. Chemosphere. 2018;213:423–33.

    Article  CAS  PubMed  Google Scholar 

  32. Gitawati R. Pattern of household drug storage. Kesmas: Natl Public Health J. 2014;9(1):27–31.

    Google Scholar 

  33. Mobrad AM, Ahmad F, Saleh SA, Rammah AAAA, Syed W, Samreen S. Unused and expired medicines: investigating the knowledge and practice of general community. Lat Am J Pharm. 2020;39(3):526–31.

    Google Scholar 

  34. Martins RR, Farias AD, Oliveira YMDC, Diniz RS, Oliveira AG. Prevalence and risk factors of inadequate medicine home storage: a community-based study. Rev Saude Publica. 2017;51:95–102.

    Article  PubMed  PubMed Central  Google Scholar 

  35. De Bolle L, Mehuys E, Adriaens E, Remon JP, Van Bortel L, Christiaens T. Home medication cabinets and self-medication: a source of potential health threats? Ann Pharmacother. 2008;42(4):572–9.

    Article  PubMed  Google Scholar 

  36. Constantino VM, Fregonesi BM, Tonani KADA, Zagui GS, Toninato APC, Nonose ERDS, et al. Storage and disposal of pharmaceuticals at home: a systematic review. Cien Saude Coletiva. 2020;25(2):585–94.

    Article  Google Scholar 

  37. Cameli D, Francis M, Francois VE, Medder NR, Von Eden L, Truglio-Londrigan M. A systematic review of medication reconciliation strategies to reduce medication errors in community dwelling older adults. JBI Evid Synth. 2012;10(42):1–18.

    Google Scholar 

  38. Ocan M, Bwanga F, Gs B, Bagenda D, Waako P, Ogwal-Okeng J, et al. Patterns and predictors of self-medication in Northern Uganda. PLoS One. 2014;9(3):e92323.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Alvim HGO, Carvalho MJP. The importance of pharmacist orientation on the correct use of medicines. Rev JRG Estud Acad. 2019;2(4):172–9.

    Google Scholar 

  40. Locquet M, Honvo G, Rabenda V, Van Hees T, Petermans J, Reginster JY, et al. Adverse health events related to self-medication practices among elderly: a systematic review. Drugs Aging. 2017;34(5):359–65.

    Article  PubMed  Google Scholar 

  41. Albawani SM, Hassan YB, Abd-Aziz N, Gnanasan S. Self-medication practice among consumers in Sana’a City. Int J Pharm Pharm Sci. 2016;8(10):119–24.

    Article  Google Scholar 

  42. Almohammed RA, Bird EL. Public knowledge and behaviours relating to antibiotic use in gulf cooperation council countries: a systematic review. J Infect Public Health. 2019;12(2):159–66.

    Article  PubMed  Google Scholar 

  43. Kheir N, El Hajj M, Wilbur K, Rm K, Yousif A. An exploratory study on medications in Qatar homes. Drug Healthc Patient Saf. 2011;3:99–106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Aditya S, Singh H. Safe medication disposal: need to sensitize undergraduate students. Int J Pharm Life Sci. 2013;4(3):2476–80.

    Google Scholar 

  45. Bertolin P, Kronbauer EAW, Pegoraro T. Disposal of home medicines in a municipality in the Paraná state. Conex Cienc. 2016;10(2):26–39.

    Article  Google Scholar 

  46. Pinto GMF, Silva KR, Pereira RFAB, Sampaio SI. Study of residential expired medicines disposal in Paulínia (SP) area, Brazil. Eng Sanit Ambient. 2014;19(3):219–24.

    Article  Google Scholar 

  47. Ferreira C, Santos MAS, Rodrigues SC. Analysis of the population's knowledge about drug disposal in Belo Horizonte - Minas Gerais. Rev Interfaces Cient Saude Ambient. 2015;3(2):9–18.

    Article  Google Scholar 

  48. Falqueto E, Kligerman DC, Assumpção RF. How to do the correct discard of medicine residues? Cien Saude Colet. 2010;15:3283–93.

    Article  PubMed  Google Scholar 

  49. Tong AYC, Peake BM, Braund R. Disposal practices for unused medications around the world. Environ Int. 2011;37(1):292–8.

    Article  PubMed  Google Scholar 

  50. Ramos HMP, Cruvinel VRN, Meiners MMMA, Queiroz CA, Galato D. Medication disposal: a reflection about possible sanitary and environmental risks. Ambient Soc. 2017;20(4):145–68.

    Article  Google Scholar 

  51. Moreira TS, Cid YP, Pierre MBR, Sousa VP, Kummerle AE, Fraga CAM. Extraction and purification of selectives ciclooxigenase-2 nonsteroidal antiinflammatory drugs. Quim Nova. 2009;32(5):1324–8.

    Article  CAS  Google Scholar 

  52. Caiazzo E, Ialenti A, Cicala C. The relatively selective cyclooxygenase-2 inhibitor nimesulide: What’s going on? Eur J Pharmacol. 2019;848:105–11.

    Article  CAS  PubMed  Google Scholar 

  53. Holloway K, Van Dijk L. The world medicines situation 2011 - Rational use of medicines. Geneva: (WHO/EMP/MIE/2011.2.2); 2011.

    Google Scholar 

  54. Kwon J, Kim S, Yoo H, Lee E. Nimesulide-induced hepatotoxicity: a systematic review and meta-analysis. PLoS One. 2019;14(1):e0209264.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Hamm JT, Ceger P, Allen D, Stout M, Maull EA, Baker G, et al. Characterizing sources of variability in zebrafish embryo screening protocols. ALTEX Altern Anim Ex. 2019;36(1):103–20.

    Google Scholar 

  56. Li Q, Wang P, Chen L, Gao H, Wu L. Acute toxicity and histopathological effects of naproxen in zebrafish (Danio rerio) early life stages. Environ Sci Pollut Res. 2016;23(18):18832–41.

    Article  CAS  Google Scholar 

  57. Zhou S, Chen Q, Di Paolo C, Shao Y, Hollert H, Seiler TB. Behavioral profile alterations in zebrafish larvae exposed to environmentally relevant concentrations of eight priority pharmaceuticals. Sci Total Environ. 2019;664:89–98.

    Article  CAS  PubMed  Google Scholar 

  58. Cha Y, Kim S, Solnica-Krezel L, DuBois RN. Cyclooxygenase-1 signaling is required for vascular tube formation during development. Dev Biol. 2005;282(1):274–83.

    Article  CAS  PubMed  Google Scholar 

  59. David A, Pancharatna K. Developmental anomalies induced by a non-selective COX inhibitor (ibuprofen) in zebrafish (Danio rerio). Environ Toxicol Pharmacol. 2009;27(3):390–5.

    Article  CAS  PubMed  Google Scholar 

  60. Nowakowska K, Giebułtowicz J, Kamaszewski M, Adamski A, Szudrowicz H, Ostaszewska T, et al. Acute exposure of zebrafish (Danio rerio) larvae to environmental concentrations of selected antidepressants: bioaccumulation, physiological and histological changes. Comp Biochem Phys C Toxicol Pharmacol. 2020;229:1086702.

    Google Scholar 

  61. Glickman NS, Yelon D. Cardiac development in zebrafish: coordination of form and function. Semin Cell Dev Biol. 2002;13(6):507–13.

    Article  PubMed  Google Scholar 

  62. Denvir MA, Tucker CS, Mullins JJ. Systolic and diastolic ventricular function in zebrafish embryos: influence of norepenephrine, MS-222 and temperature. BMC Biotechnol. 2008;8(1):21–9.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Rubinstein AL. 2006. Zebrafish assays for drug toxicity screening. Expert Opin Drug Met Toxicol. 2006;2(2):231–40.

    Article  CAS  Google Scholar 

  64. Raldúa D, André M, Babin PJ. Clofibrate and gemfibrozil induce an embryonic malabsorption syndrome in zebrafish. Toxicol Appl Pharmacol. 2008;228(3):301–14.

    Article  PubMed  Google Scholar 

  65. Kodde IF, van der Stok J, Smolenski RT, de Jong JW. Metabolic and genetic regulation of cardiac energy substrate preference. Comp Biochem Phys A Physiol. 2007;146(1):26–39.

    Article  Google Scholar 

  66. Adema-Hannes R, Shenker J. Acute lethal and teratogenic effects of tributyltin chloride and copper chloride on mahi mahi (Coryphaena hippurus) eggs and larvae. Environ Toxicol Chem. 2008;27(10):2131–5.

    Article  CAS  PubMed  Google Scholar 

  67. Chang C, Wu SL, Zhao XD, Zhao CT, Li YH. Developmental toxicity of doxorubicin hydrochloride in embryo-larval stages of Zebrafish. Biomed Mater Eng. 2014;24(1):909–16.

    CAS  PubMed  Google Scholar 

  68. Seok SH, Baek MW, Lee HY, Kim DJ, Na YR, Noh KJ, et al. In vivo alternative testing with zebrafish in ecotoxicology. J Vet Sci. 2008;9(4):351–7.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Lei M, Zhang L, Lei J, Zong L, Li J, Wu Z, et al. Overview of emerging contaminants and associated human health effects. Biomed Res Int. 2015;404796.

  70. Beyer J, Petersen K, Song Y, Ruus A, Grung M, Bakke T, et al. Environmental risk assessment of combined effects in aquatic ecotoxicology: a discussion paper. Mar Environ Res. 2014;96:81–91.

    Article  CAS  PubMed  Google Scholar 

  71. Daughton CG, Ruhoy IS. Green pharmacy and pharmEcovigilance: prescribing and the planet. Expert Rev Clin Pharmacol. 2011;4(2):211–32.

    Article  PubMed  Google Scholar 

  72. Marques R, Xavier CR. Socio-environmental responsibility from the use and disposal of medicines. Braz J Environ Educ. 2018;13(4):174–89.

    Google Scholar 

  73. Jackson JS, Kennedy CJ. Regulation of hepatic abcb4 and cyp3a65 gene expression and multidrug/multixenobiotic resistance (MDR/MXR) functional activity in the model teleost, Danio rerio (zebrafish). Comp Biochem Phys C Toxicol Pharmacol. 2017;200:34–41.

    Article  CAS  Google Scholar 

  74. Koopaei NN, Abdollahi M. Health risks associated with the pharmaceuticals in wastewater. DARU J Pharm Sci. 2017;25(1):9.

    Article  Google Scholar 

  75. Florea M, Monciu CM, Andritoiu ML, Bacanu LG. Spectrophotometric determination of nimesulide through ion-pair complex formation with hexadecyltrimethylammonium bromide. Farmacia. 2008;56(6):639–46.

    CAS  Google Scholar 

Download references

Acknowledgements

This study received financial support in part from the Coordination for the Improvement of Higher Education Personnel - Brazil (CAPES) - Financial Code 001. Furthermore, we are most grateful for the financial support of the Minas Gerais Research Support Foundation, concession number CVZ_APQ-03548- 16.; and the grant number of the National Council for Scientific and Technological Development CNPq (process 405822 / 2016-2). We would also like to thank the Tissue Processing Laboratory (LAPROTEC) for the equipment, materials, support and the team who were of great importance and assistance during this study. We extend our gratitude especially to master students Anderson Kelvin Saraiva Macêdo, Isabella Ferreira Silva, and professor Dra. Farah Maria Drumond Chequeer Baldoni.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hélio Batista Santos.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Salgado, M.A.R., Salvador, M.R., Baldoni, A.O. et al. Evaluation of the potential environmental risk from the destination of medicines: an epidemiological and toxicological study. DARU J Pharm Sci 29, 61–71 (2021). https://doi.org/10.1007/s40199-020-00383-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40199-020-00383-4

Keywords

Navigation