Ecotoxicological evalution of tuberculostatic medicines: Predicted Environmental Concentration and biological effects in Daphnia similis and Echinometra lucunter.
DOI:
https://doi.org/10.33448/rsd-v10i5.14825Keywords:
Isoniazid; Pyrazinamide; Pharmaceuticals in the environment; Predicted Environmental Concentration; Ecotoxicology.Abstract
The increase in the production of pharmaceutical products has been gradually increasing and, consequently, the residues of these products inappropriately in the aquatic environment as well. In this context, the scarcity of ecotoxicological studies on drugs of the tuberculostatic class in the aquatic environment is highlighted. Thus, the present study aimed to evaluate the presence of tuberculostatic drugs used as a standardized scheme by the Brazilian Ministry of Health for the treatment of tuberculosis (Rifampicin, Isoniazid, Pyrazinamide and Etambutol), by calculating the predicted environmental concentration (PEC) in surface waters of the municipality from Cubatão (São Paulo, Brazil). In addition, adverse biological effects on the test organisms Daphnia similis and Echinometra lucunter for the drugs Isoniazid and Pyrazinamide were evaluated. The PEC values were calculated among the four tuberculostatic drugs according to the guideline of the European Medicines Agency (EMEA) (CHMP, 2006). Afterwards, toxicity tests were performed on D. similis and E. lucunter according to Brazilian Association of Technical Standards ABNT NBR 12713:2016 e ABNT NBR 15350:2012, respectively. PEC values for all four tuberculostatic drugs included in the present study showed values that exceeded the limit considered by the EMEA of 0.01 µg.L-1. For the toxicity test with D. similis, the drugs Isoniazid and Pyrazinamide presented EC50 values of 69.97 mg.L-1 and 44.49 mg.L-1, respectively, being classified as “harmful” according to the Directive of the European Economic Community (EEC) 93/67 / EEC. As for the toxicity test with E. lucunter, the drugs Isoniazid and Pyrazinamide showed IC50 values of 23.66 mg.L-1 and 17.21 mg.L-1, respectively, results that are also considered “harmful” according to with Directive 93/67 / EEC. The results of this research may serve as subsidies to new legislation and the creation of government programs that seek solutions promoting reduction and even the elimination of pharmaceuticals in the aquatic environment.
References
ABNT NBR – Associação brasileira de normas técnicas. (2012). Ecotoxicologia aquática – Toxicidade crônica de curta duração – Método de ensaio com ouriço-do-mar Echinometra lucunter. 15350:2012 Brasil; 2012 p. 21.
ABNT NBR - Associação brasileira de normas técnicas. (2016). Ecotoxicologia aquática – Toxicidade aguda - Método de ensaio com Daphnias spp. (Cladócera, Crustácea). 12713:2016 Brasil; 2004 p. 33
Agência Nacional de Vigilância Sanitária (ANVISA). (2003). http://www.anvisa.gov.br/legis/resol/2003/rdc/136_03rdc.htm
Agência Nacional de Vigilância Sanitária (ANVISA). (2010). http://portal.saude.gov.br/portal/arquivos/pdf/rename2010final.pdf
Baumann, L., Holbech, H., Posthaus, H. S., Moissi, A. P., Hennies, M., Tidermann, J., Segner, H. & Braunbeck, T. (2020). Does hepatotoxicity interfere with endocrine activity in zebrafish (Danio rerio)? Chemosphere. 238(1), 124-589
Carvalho, G. G., Pires, A. J. V., Garcia, R., Veloso, C. M., Silva, R. R., Mendes, F. B. L., Pinheiro, A. A. & Souza, D. R. (2009). In situ degradability of dry matter, crude protein and fibrous fraction of concentrate and agroindustrial by-products. Ciência Anim. Bras. 10, 689-97
CEC (Commission of the european communities). Technical guidance document in support of commission directive 93/67/EEC on risk assessment for new notified substances. Part II, environmental risk assessment. Luxembourg: Office for official publication of the European Communities, v. 1488, p. 94, 1996.
CHMP – Guideline on the environmental risk assessment of medicinal products for huma use. (2006). http://www.emea.eu.int/pdfs/human/swp/444700en.pdf.
Companhia Ambiental do Estado de São Paulo (CETESB). (2007). Relatório de monitoramento de emissários submarinos. http://www.cetesb.sp.gov.br/agua/praias/25-publicacoes-/-relatorios
EMEA – European medicines agency, committee for medicinal products for human use (CHMP) – Guideline on the environmental Risk Assessment - . (2006). https://www.ema.europa.eu/en/environmental-risk-assessment-medicinal-products-human-use.
Environmental Protection Agency (EPA). (2007). Method 1694: Pharmaceuticals and Personal Care Products in Water, Soil, Sediment, and Biosolids by HPLC/MS/MS. http://water.epa.gov/scitech/methods/cwa/ppcp/index.cfm
Escher, M.A. S., et al (2019). Problematica ambiental da contaminação dos recursos hídricos por fármacos. RBCIAMB. 51, 141-148.
European agency for the evaluation of medicinal products (EMEA). Note for guidance on environmental risk assessment of medicinal products for human use. (2005). http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/10/WC500003978.pdf
Fent, K., Weston, A. A. & Caminada, D. (2006). Ecotoxicology of human pharmaceuticals. Aquatic Toxicology. 76, 122-159.
Garrison, A. W., Pope, J. D., Allen, F. R. & Keith, C. H. (1976). Identification and analysis of organic pollutants in water. Michigan: Ann Arbor Science. 5, 517-566.
Hamilton, A. M., Russo, R. C. & Thurston, R. V. (1977). Trimmed Sperarman-Karber method for estimating median lethal concentrations in toxicity bioassays. Environmental Sciente e Technology. 11(7), 714-719.
IMS Health – The pharmerging future, Pharmaceutical Executive. (2009) http://www.pharmexec.com/pharmexec/issue/issueDetail.jsp?id=17680
IMS Health – Saiba o que impulsiona o sistema de saúde brasileiro. (2011). http://www.imshealth.com/portal/site/ims/menuitem.d248e29c86589c9c 30e81c033208c22a/?vgnextoid=c42ae9161a3f2310VgnVCM100000ed152ca2RCRD&cpsextcurrchannel=1
Jones, O.A.H., Voulvoulis, N. & Lester, J. N. (2007). Ecotoxicity of pharmaceuticals. Comprehensive Analytical Chemistry. 50, 387-424.
Brasil. Ministério da Saúde. (2019). Manual de Recomendações para o controle da Tuberculose no Brasil. https://bvsms.saude.gov.br/bvs/publi cacoes/manual_rec omendacoes_controle_tuberculose_brasil_2_ed.pdf
Newman, M.C. & UNGER, M.A. (2002). Fundamentals of Ecotoxicology. Lewis Publisher.
Norberg-King, T. (1988). An interpolation estimate for chronic toxicity: The ICp approach. National Effluente Toxicity Assessment Center. 05-88.
Organização mundial da saúde (OMS). (2012). Pharmaceuticals in Drinking-water. Genebra. Health and Environment Water, Sanitation, Hygiene and Health.
Organização Mundial da Saúde (OMS). (2014). Antimicrobial Resistance: global reporto n surveillance. Genebra. Library Cataloguingin Publication.
Parlamento Europeu. Diretiva 2013/39/UE - Altera as Diretivas 2000/60/CE e 2008/105/CE no que respeita às substâncias prioritárias no domínio da política da água. (2013). Jornal Oficial da União Europeia. https://eur-lex.europa.eu/legal content/PT/TXT/PDF/?uri=CELEX:32013L0039efrom=IT.
Pereira, C. D. S. (2008). Biomarcadores de exposição, efeito e bioacumulação de xenobióticos em mexilhões Perna perna (Linnaeus, 1758) transplantados ao longo do litoral de São Paulo. Tese doutorado, Universidade de São Paulo, USP.
Pereira A. S. et al. (2018). Metodologia da pesquisa científica. UFSM
Quintino, M. P. (2003). Effects of pyrazinamide on pregnant albino rats. International Journal of Morphology. 21(4) 299-302.
Reis-Filho, R. W., Barreiro, J. C., Vieira, E. M. & Cass, Q. B. (2007). Fármacos, ETEs e corpos hídricos. Revista Ambiente & Água. 2. 54-61.
SABESP-Companhia de Saneamento Básico do Estado de São Paulo. (2018). Tratamento de esgotos. Recuperado de http://site.sabesp.com.br/site/interna/Default.aspx?secaoId=49.
Santos, L. H. M., Araújo, A. B., Fachini, A., Pena, A., Deleurematos, C. & Montenegro, M. C. B. S. M. (2010). Ecotoxicological aspects related to the presence of pharmaceutical in the aquatic environment. Journal of Harzardous Materials. 75(1) 45-95.
Scheffer, E. W & Tiburtius, E. R. (2014). Triclosan: Fate in the Environmentand Perspectives in the Treatment of Public Water Supply. Revista de Química. 6(5), 1144-1159
Sea Urchin Genome Sequencing Consortium. (2006). The genome of the sea urchin Strongylocentrotus purpuratus. Science. 314 (5801), 941-952.
Sindicato da Indústria de Produtos Farmacêuticos do Estado de São Paulo (SINDUSFARMA). (2012). http://www.sindusfarmacomunica.org.br/indicadores-economicos/
USEPA - United States Environmental ProtectionAgency. (2002) EPA/600/4-91/003 — Short-termmethods for estimating the chronic toxicity of effluents and receiving waters to marine and estuarine organisms. Cincinati: U.S. Environmental Protection Agency. pp. 579.
UEPA – U.S. Environmental protection agency. (2009). Sperm cell toxicity testes using the sea urchin (arbacia puntuctulata). https://www.epa.gov/sites/production/files/201509/documents/seaurchintesting.pdf.
Yamamoto, N. S., et al (2012). Avaliação dos esfeitos biológicos dos fármacos Losartan em microcrustáceos Daphnia similis e Ceriodpahnia dúbia *Crustacea, Cladocera). Unisanta BioScience. 1(2), 49-53
Zhao, H., et al (2017). Pyrazinamide-induced hepatotoxicity and gender diferences in rats as revealed by a HNMR based metabolomics approach. Toxicological Research. Toxicology Reserach, 6(1), 17–29.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2021 Monike Silva de Freitas; Walber Toma; Fábio Hermes Pusceddu; Luciana Lopes Guimarães
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.