The toxic effects of the antiretroviral nevirapine and a nevirapine-based drug for aquatic organisms

Authors

DOI:

https://doi.org/10.33448/rsd-v11i2.25014

Keywords:

Aquatic toxicity; Environmental safety; Ecotoxicity; Micropollutants.

Abstract

The aquatic toxicity of active pharmaceutical ingredients (APIs) and drugs is little discussed in literature. Nevirapine (NVP) is an antiretroviral, non-nucleoside reverse transcriptase inhibitor. This study evaluated the aquatic toxicity of this API alone and as an NVP-based drug. For this purpose, we analyzed the effects on the viability of the aquatic organisms Chlorella vulgaris, Artemia salina and Aliivibrio fischeri. The observed effects were, per organisms: the growth inhibition tests for 72 h for the microalgae C. vulgaris; the mortality for 24 h for the microcrustacean A. salina; and the bioluminescence inhibition test for 15 min for the bacteria A. fischeri. The non-parametric log-logistic dose-response statistical model was used to obtain effective concentrations (EC) of 50% and 10%, for NVP API and for the NVP-based drug. Isolated NVP affected the viability of three studied species; on the other hand, the drug based on NVP was not toxic to A. salina. It is noteworthy that the EC50% of NVP differed statistically between the API and the drug for A. fischeri and A. salina. It was also observed that there is a narrow concentration range between the appearance of the first observable effects and the toxic effects of NVP in these species. This reinforces the importance of studying and controlling the release of this API into the environment. Finally, it was concluded that it is possible to implement monitoring of the environmental toxicity of micropollutants in the industrial routine, using standardized and economically accessible toxicity tests, which offer speed and practicality in the analysis of effluents.

Author Biographies

Leonardo Alvarenga de Paula Freitas, Fundação Ezequiel Dias

Analytical Development and Stability Studies of the Drug Product Develompment Division of Industrial Direcotrate, Ezequiel Dias Foundation, Belo Horizonte, Minas Gerais, Brazil

Izabela Cristina Dias Vaz, Universidade Federal de Minas Gerais

Environmental Analyst registered in CRBio4, I have 8 years of experience in limnology. Specifically I provide services of systematic and taxonomic analysis of zooplankton, cyanobacteria and microalgae.

Francisco Antônio Rodrigues Barbosa, Universidade Federal de Minas Gerais

He has a degree in Natural History from the Federal University of Minas Gerais (1973), a master's degree in Ecology and Natural Resources from the Federal University of São Carlos (1979), a doctorate in Ecology and Natural Resources from the Federal University of São Carlos (1981), and a post-doctorate degree in algal ecophysiology from the Institute of Freshwater Ecology-England. He is currently researcher 1 B of the National Council for Scientific and Technological Development, full professor at the Federal University of Minas Gerais and coordinator of the specialization course in Municipal Water Resources Management at ICB/UFMG. 

Marcos Paulo Gomes Mol, Fundação Ezequiel Dias

Graduated in Environmental Engineering from the Federal University of Ouro Preto - UFOP (2006), Master (2011) and PhD (2016) in Sanitation and Environment from the Federal University of Minas Gerais - UFMG; performed a sandwich PhD at the London School of Hygiene and Tropical Medicine, UK (2015-2016), under the mentorship of Prof. Sandy Cairncross. He was coordinator of the Environmental Management Unit of the Ezequiel Dias Foundation (FUNED) in Belo Horizonte, (2007 to 2015) and is currently a researcher at FUNED, coordinating the Health and Environment Research Group, accredited in CNPq. He also teaches in the Professional Master's Degree program in Biotechnology at FUNED.

Sérgia Maria Starling Magalhães, Universidade Federal de Minas Gerais

Bachelor's degree in Pharmacy from the Federal University of Minas Gerais (1986), Master's degree in Chemistry from the Federal University of Minas Gerais (1991) and PhD in Chemistry from the Federal University of Minas Gerais (1996). He is currently an associate professor at the Federal University of Minas Gerais. He works in the field of Pharmacy, with emphasis on public health and environment. He works mainly on the following topics: drug utilization studies and environment and health. He coordinates the institution's water analysis laboratory and conducts research in the area of biodegradation/bioremediation of aquatic pollutants using cyanobacteria.

Micheline Rosa Silveira, Universidade Federal de Minas Gerais

Graduated in Pharmacy with Qualification in Clinical Analysis from the Federal University of Ouro Preto (1995), with master's degree (1997) and doctorate (2002) in Biological Sciences (Physiology and Pharmacology) from the Federal University of Minas Gerais (UFMG). Professor at UFMG since 2006. Associate Professor at the Department of Social Pharmacy - UFMG. Researcher at the Pharmacoepidemiology Research Group (GPFE) of the School of Pharmacy - UFMG. She has experience in the areas of Medications and Pharmaceutical Assistance, with emphasis on Pharmaceutical Assistance and Infectious Diseases. Currently, she is Vice-Director of the School of Pharmacy - UFMG.

References

Abbas, M., Adil, M., Ehtisham-ul-Haque, S., Munir, B., Yameen, M., Ghaffar, A., Shar, G. A., Tahir, M. A. & Iqbal M. (2018). Vibrio fischeri bioluminescence inhibition assay for ecotoxicity assessment: A review. Sci. Total Environ. 626: 1295-1309. DOI: https://doi.org/10.1016/j.scitotenv.2018.01.066

Amarante, C. B., Müller, A. H., Póvoa, M. M. & Dolabela, M. F. (2011) Estudo fitoquímico biomonitorado pelos ensaios de toxicidade frente à Artemia salina e de atividade antiplasmódica do caule de aninga (Montrichardia linifera). Acta Amazonica. 41, 3, 431-434. DOI: https://doi.org/10.1590/S0044-59672011000300015>

ANSES - Agence Nationale de Securite Sanitaire. (2013). National analysis campaign on drug residues in water intended for human consumption. Retrieved May 6, 2020, from www.anses.fr/en/content/national-analysis-campaign-drug-residues-water-results-line-expectation.

Awodele, O., Popoola, T., Rotimi, K., Ikumawoyi, V. & Okunowo, W. (2015). Antioxidant modulation of nevirapine induced hepatotoxicity in rats. Interdisciplinary Toxicology, 8(1), 8–14. DOI: https://doi.org/0.1515/intox-2015-0002

BIO Intelligence Service. (2013). Study on the environmental risks of medicinal products, Final Report prepared for Executive Agency for Health and Consumers.

Boehringer Ingelheim, Vetmedica. Safety data sheet United States nevirapine. Version 1. (2015). Retrived 2020, from https://www.bi-vetmedica.com/sites/default/files/MSDS/nevirapine-sds-us.pdf

Boehringer Ingelheim, Viramune® (nevirapine) Tablets/Viramune® (nevirapine) oral suspension, U.S. prescribing information. (2019) Retrived 2020, from https://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Viramune/Viramune.pdf

Boxall, A. B. A., Keller, V. D. J., Strau, J. O., Monteiro, S. C., Fussell, R. & Williams, R. J. (2014). Exploiting monitoring data in environmental exposure modelling and risk assessment of pharmaceuticals. Environment International, 73: 176-185. DOI: https://doi.org/10.1016/j.envint.2014.07.018.

Costa, C. R., Olivi P., Botta, C. M. R. & Espindola, E. L. G. (2008). Toxicity in aquatic environments: Discussion and evaluation methods. Química Nova, 31: 1820-1830. DOI: https://doi.org/10.1590/S0100-40422008000700038.

Czech, B., Jośko, I. & Oleszczuk, P.( 2014). Ecotoxicological evaluation of selected pharmaceuticals to Vibrio fischeri and Daphnia magna before and after photooxidation process. Ecotoxicology and Environmental Safety, 104: 247-253. DOI: https://doi.org/10.1016/j.ecoenv.2014.03.024

Darienko, T., Rad-Menéndez, C., Campbell, C., & Pröschold, T. (2019). Are there any true marine Chlorella species? Molecular phylogenetic assessment and ecology of marine Chlorella-like organisms, including a description of Droopiella gen. nov. Systematics and Biodiversity, 17(8), 811–829. DOI: https://doi.org/10.1080/14772000.2019.1690597

Das, K., Martinez, S. E., Bauman, J. D. & Arnold, E. (2012). HIV-1 reverse transcriptase complex with DNA and nevirapine reveals non-nucleoside inhibition mechanism. Nature Structural & Molecular Biology, 19: 253–259. DOI: https://doi.org/10.1038/nsmb.2223

de García, S. O., García-Encina, P. A. & Irusta-Mata, R. (2016). Dose-response behavior of the bacterium Vibrio fischeri exposed to pharmaceuticals and personal care products. Ecotoxicology, 25: 141– 790 162. DOI: https://doi.org/10.1007/s10646-015-1576-8

del Valle, L. G., Hernández, R. G. & Ávila, J. P. (2013). Oxidative stress associated to disease progression and toxicity during antiretroviral therapy in human immunodeficiency virus infection. Journal of Virology & Microbiology, 2013, 279685, 15. DOI: https://doi.org/10.5171/2013.279685

Dong, Y., Fang, Z., Xu, Y., Wang, Q. & Zou, X. (2019). The toxic effects of three active pharmaceutical ingredients (APIs) with different efficacy to Vibrio fischeri. Emerg. Contam. 5: 297-302. DOI: https://doi.org/10.1016/j.emcon.2019.08.004

Du, J., Yuan, Y., Si, T., Lian, J. & Zhao, H. (2012). Customized optimization of metabolic pathways by combinatorial transcriptional engineering. Nucleic Acids Research, 40: 142. DOI: https://doi.org/10.1093/nar/gks549

Dunn, A. K. (2012). Vibrio fischeri metabolism: symbiosis and beyond. Advances in microbial physiology, 61: 37–68. https://doi.org/10.1016/B978-0-12-394423-8.00002-0

Fernández, L. P., Brasca, R., Attademo, A. M., Peltzer, P. M., Lajmanovich, R. C. & Culzoni, M. J. (2020). Bioaccumulation and glutathione S-transferase activity on Rhinella arenarum tadpoles after 813 short-term exposure to antiretrovirals. Chemosphere, 246. 125830 DOI: https://doi.org/10.1016/j.chemosphere.2020.125830

Geiger, E., Gausterer, R. H. & Saçan, M. T. (2016). Single and mixture toxicity of pharmaceuticals and chlorophenols to freshwater algae Chlorella vulgaris. Ecotoxicology and Environmental Safety, 129: 189-198. DOI: https://doi.org/10.1016/j.ecoenv.2016.03.032

GHS (2019) Globally Harmonized System of Classification and Labelling of Chemicals. Eighth Revised Edition, United Nations, New York, DOI: https://doi.org/10.18356/f8fbb7cb-en

González, M. A., Proschold, T., Palacios, Y., Aguayo, P., Inostroza, I., & Gomez, P. I. (2013). Taxonomic identification and lipid production of two Chilean Chlorella-like strains isolated from a marine and an estuarine coastal environment. AoB Plants, 5(0), plt020–plt020. DOI: https://doi.org/10.1093/aobpla/plt020

González-González, R. B., Sharma, A., Parra-Saldívar, R., Ramirez-Mendoza, R. A., Bilal, M. & Iqbal, H. M. N. (2022). Decontamination of emerging pharmaceutical pollutants using carbon-dots as robust materials. J Hazard Mater. 5; 423 (Pt B):127145. DOI: https://doi.org/1010.1016/j.jhazmat.2021.127145.

Gupta, B. P., Lama, T. K., Adhikari, A., Shrestha, A., Rauniyar, R., Sapkota, B., Thapa, S., Shrestha, S., Gupta, P. P. & Manandhar, K. D. (2016). First report of hepatitis E virus viremia in healthy blood donors from Nepal. Virus Disease, 27: 324–326. DOI: https://doi.org/10.1007/s13337-016-0331-y

Hube, S. & Wu, B. (2021) Mitigation of emerging pollutants and pathogens in decentralized wastewater treatment processes: A review, Science of The Total Environment, 779,146545. DOI: https://doi.org/10.1016/j.scitotenv.2021.146545

Hulgan, T., Morrow, J., D’Aquila, R. T., Raffanti, S., Morgan, M., Rebeiro, P. & Haas, D. W. (2003). Oxidant stress is increased during treatment of human immunodeficiency virus infection. Clinical Infectious Diseases, 37:1711–7. DOI: https://doi.org/10.1086/379776

ISO 11348-3. (2007) Water quality – determination of the inhibitory effect of waste samples on the light emission of Vibrio fischeri (luminescent bacteria test) – part 3: method using freeze-dried bacteria. Geneva. International Organization for Standardization.

Jacob, R. S., Santos, L. V., Souza, A. F. & Lange, L. C. (2016). A toxicity assessment of 30 pharmaceuticals using Aliivibrio fischeri: a comparison of the acute effects of different formulations. Environmental tecnology, 37: 2760-2767. DOI: https://doi.org/10.1080/09593330.2016.1164249

Jain, V., Hartogensis, W., Bacchetti, P., Hunt, P. W., Hatano, H., Sinclair, E., Epling, L., Lee, T. H., Busch, M. P., McCune, J. M., Pilcher, C. D., Hecht. F. M. & Deeks, S. G. (2013). Antiretroviral therapy initiated within 6 months of HIV infection is associated with lower T-cell activation and smaller HIV reservoir size. J. Infect. Dis, 208: 1202–1211. DOI: https://doi.org/10.1093/infdis/jit311.

Jos, A., Repetto, G., Rios, J. C., Hazen, M. J., Molero, M. L., del Peso, A., Salguero, M., Fernández-Freire, P., Pérez-Martı́n, J. M. & Cameán A. (2003). Ecotoxicological evaluation of carbamazepine using six different model systems with eighteen endpoints. Toxicology in Vitro, 17: 525-532. DOI: https://doi.org/10.1016/S0887-2333(03)00119-X

Kaiser, L. E. (1998). Correlations of vibrio fischeri bacteria test data with bioassay data for other organisms. Environmental Health Perspectives, 106 (2). 583-591. Doi: https://doi.org/10.1289/ehp.98106583

Kim, S., Chen, J., Cheng, T., Gindulyte, A., He, J., He, S., Li, Q., Shoemaker, B. A., Thiessen, P. A., Yu, B., Zaslavsky, L., Zhang, J. & Bolton, E. E. (2019). PubChem 2019 update: improved access to chemical 871 data. Nucleic acids research, 47: 1102-1109. DOI: https://doi.org/10.1093/nar/gky1033

K'oreje, K. O., Demeestere, K., De Wispelaere, P., Vergeynst, L., Dewulf, J., Van Langenhove, H. (2012). From multi-residue screening to target analysis of pharmaceuticals in water: Development of a new approach based on magnetic sector mass spectrometry and application in the Nairobi River basin, Kenya. Sci. Total Environ. 437: 153-164. DOI: https://doi.org/10.1016/j.scitotenv.2012.07.052

K'oreje, K.O., Vergeynst, L., Ombaka, D., De Wispelaere, P., Okoth, M., Van Langenhove, H. & Demeestere, K. (2016). Occurrence Patterns of Pharmaceutical Residues in Wastewater, Surface Water and Groundwater of Nairobi and Kisumu City, Kenya. Chemosphere, 149: 238-244. DOI: https://doi.org/10.1016/j.chemosphere.2016.01.095

Kroeger, M. B. S., Rouze, C. A., Taneyhill, L. A., Smith, N. A., Hughes, S. H., Boyer, P. L., Janssen, P. A. J., Moereels, H., Koymans, L., Arnold, E., Ding, J., Das, K., Zhang, W., Michejda, C. J. & Smith Jr, R. H. (1995). Molecular modeling studies of HIV-1 reverse transcriptase nonnucleoside inhibitors: Total energy of complexation as a predictor of drug placement and activity. Protein Science, 4:2203-2222. DOI: https://doi.org/10.1002/pro.5560041026

Kümmerer, K. (2009). Antibiotics in the aquatic environment – A review – Part I. Chemosphere, 75: 417-434. DOI: https://doi.org/10.1016/j.Chemosphere.2008.11.086

Leitão, J. M. M. & Silva, J. C. G. E. (2010). Firefly luciferase inhibition. Journal of Photochemistry and Photobiology B: Biology, 101: 1-8. DOI: https://doi.org/10.1016/j.jphotobiol.2010.06.015

Li, T., Xu, G., Rong, J., Chen, H., He, C., Giordano, M., Wang, Q. (2016). The acclimation of Chlorella to high-level nitrite for potential application in biological NOx removal from industrial flue gases. Journal of Plant Physiology, 195: 73-79. DOI: https://doi.org/10.1016/j.jplph.2016.03.006

Libralato, G., Prato, E., Migliore, L., Cicero, A. & Manfra, L. (2016). A review of toxicity testing protocols and endpoints with Artemia spp. Ecolological Indicators, 69: 35-49. DOI: https://doi.org/10.1016/j.ecolind.2016.04.017

Lu, Y., Xu, X., Meng, C., Zhou, J., Sheng, J., Wu, C. &, Xu, S. (2013). The toxicity assay of Artemia salina as a biological model for the preliminary toxic evaluation of chemical pollutants. Advanced Materials Research, 726–731, 230–233. DOI: https://doi.org/10.4028/www.scientific.net/AMR.726-731.230

Luo, Y., Guo, W., Ngo, H. H., Nghiem, L. D., Hai, F. I., Zhang, J., Liang, S. & Wang, X. C. (2014). A review on the occurrence of micropollutants in the aquatic environment and their fate and removal during wastewater treatment. Science of The Total Environment, 473-474, 619–641. DOI: https://doi.org/10.1016/j.scitotenv.2013.12.065.

Marques, S. M. & Silva, J. C. G. E. (2009). Firefly bioluminescence: A mechanistic approach of luciferase catalyzed reactions. IUBMB Life, 61: 6-17. DOI: https://doi.org/10.1002/iub.134

Martins, A. C. R., da Costa, J. K. N., Herbert, A., Farias, F. R. S., Rezende, M., Kozlowski Junior, V. A. & de Geus, J. L. (2021) Toxicity assessment of mastic and pomegranate tinctures using the Artemia salina bioassay. Research, Society and Development, [S. l.], 10, 3, e5201031375. DOI: https://doi.org/10.33448/rsd-v10i3.13751.

Meyer, B., Ferrigni, N., Putnam, J., Jacobsen, L., Nichols, D. & McLaughlin, J. (1982). Brine Shrimp: A Convenient General Bioassay for Active Plant Constituents. Planta Medica, 45: 31–34. DOI: https://doi.org/10.1055/s-2007-971236

Minagh, E., Hernan, R., O'Rourke, K., Lyng, F. M. & Davoren, M. (2009). Aquatic ecotoxicity of the selective serotonin reuptake inhibitor sertraline hydrochloride in a battery of freshwater test species. Ecotoxicology and environmental safety, 72: 434–440. DOI: https://doi.org/10.1016/j.ecoenv.2008.05.002

Minguez, L., Pedelucq, J., Farcy, E., Ballandonne, C., Budzinski, H. & Halm-Lemeillz, M. P. (2016). Toxicities of 48 pharmaceuticals and their freshwater and marine environmental assessment in northwestern France. Environmental Science and Pollution Research, 23: 4992–5001. DOI: https://doi.org/10.1007/s11356-014-3662-5

Ngumba, E., Gachanja, A. & Tuhkanen, T. (2016). Occurrence of selected antibiotics and antiretroviral drugs in Nairobi River Basin, Kenya. Science of the Total Environ, 539: 206–213. DOI: https://doi.org/10.1016/j.scitotenv.2015.08.139

Nie, X., Wang, X., Chen, J., Zitko, V. & An T. (2008). Response of the freshwater alga Chlorella vulgaris to trichloroisocyanuric acid and ciprofloxacin. Environmental Toxicology and Chemistry, 27: 168-173. DOI: https://doi.org/10.1897/07-028.1

Nunes-Halldorson, V. S. & Duran, N. L. (2003). Bioluminescent bacteria: lux genes as environmental biosensors. Braz. J. Microbiol., 34: 91-96. DOI: https://doi.org/10.1590/S1517-83822003000200001

Nunes, B. S., Carvalho, F. D., Guilhermino, L. M. & Van Stappen, G. (2006). Use of the genus Artemia in ecotoxicity testing. Environmental pollution, 144: 453–462. DOI: https://doi.org/10.1016/j.envpol.2005.12.037

Oliveira, G. A. R., Leme, D. M., de Lapuente, J., Brito, L. B., Porredón, C., Rodrigues, L. B., Brull, N., Serret, J. T., Borràs, M., Disner, G. R., Cestari, M. M. & Oliveira, D. P. (2018). A test battery for assessing the ecotoxic effects of textile dyes. Chem Biol Interact. 1;291:171-179. Doi: https://doi.org/10.1016/j.cbi.2018.06.026.

Onbasili, D. & Duman, F. (2010). Acute toxicity of some insecticides on Artemia salina and Daphnia magna. Fresenius Environmental Bulletin. 19 (11): 2608-2610

Organisation for Economic Co-operation and Development – OECD. (2011). Guidelines for testing chemicals freshwater alga and cyanobacteria growth inhibition test. 201. Retrived from https://www.oecd-ilibrary.org/docserver/9789264069923-en.pdf?expi

Parvez, B. S., Venkataraman, C. & Mukherji, S. (2005). A review on advantages of implementing luminescence inhibition test (Vibrio fischeri) for acute toxicity prediction of chemicals. Environment International, 32, 265 – 268. Doi: https://doi.org/10.1016/j.envint.2005.08.022

Pavlaki, M. D., Pereira, R., Loureiro, S. & Soares, A. M. (2011). Effects of binary mixtures on the life traits of Daphnia magna. Ecotoxicology and environmental safety, 74: 99–110. Doi: https://doi.org/10.1016/j.ecoenv.2010.07.010

Prasse, C., Schlüsener, M. P., Schulz, R. & Ternes, T. A. (2010). Antiviral Drugs in Wastewater and Surface Waters: A New Pharmaceutical Class of Environmental Relevance? Environmental science & technology, 44: 1728-1735. Doi: https://doi.org/10.1021/es903216p

Rajabi, S., Ramazani, A., Hamidi, M. & Naji, T. (2015) Artemia salina as a model organism in toxicity assessment of nanoparticles. DARU J Pharm Sci 23, 20. Doi: https://doi.org/10.1186/s40199-015-0105-x

Ribo, J. M. (1997). Interlaboratory Comparison Studies of the Luminescent Bacteria Toxicity. Bioassay. Environmental Toxicology and Water Quality, 12(4), 283–294. Retrived 2020, from https://jglobal.jst.go.jp/en/detail?JGLOBAL_ID=200902141905826462

Rippka, R., Deruelles, J. & Waterbury, J. B. (1979). Generic Assignments, Strain Histories and Properties of Pure Cultures of Cyanobacteria. Journal of sant General Microbiology, 111: 61. Doi: https://doi.org/10.1099/00221287-111-1-1

Ritz, C., Baty, F., Streibig, J. C. & Gerhard, D. (2015). Dose-Response Analysis Using R. PLoS ONE, 10: e0146021. Doi: https://doi.org/10.1371/journal.pone.0146021

Rodrigues, M. O., Gonçalves, A. M. M.,Gonçalves, F. J. M., Nogueira, H., Marques, J. C. & Abrantes, N.(2018). Effectiveness of a methodology of microplastics isolation for environmental monitoring in freshwater systems, Ecological Indicators, 89: 488-495, ISSN 1470-160X. Doi: https://doi.org/10.1016/j.ecolind.2018.02.038.

Roede, J. R. & Miller, G. W. 2014. Diquat. Encyclopedia of Toxicology, 2. 202-204. Doi: http://dx.doi.org/10.1016/B978-0-12-386454-3.00137-8

Shea, D. (2004). Transport and Fate of Toxicants in the Environment. A Textbook of Modern Toxicology, 479–499. Doi: https://doi.org/10.1002/0471646776.ch27

Silva, A., Santos, L. H., Delerue-Matos, C.& Figueiredo, A. S. 2014. Impact of excipients in the chronic toxicity of fluoxetine on the alga Chlorella vulgaris. Environmental technology, 35: 3124-3129. Doi: https://doi.org/10.1080/09593330.2014.932438

Silva, S. R., Barbosa, F. A. R., Mol, M. P. G., Magalhães, S. M. S. (2019). Toxicity for Aquatic Organisms of Antiretroviral Tenofovir Disoproxil. Journal of Environmental Protection, 10: 1565-1577. Doi: https://doi.org/10.4236/jep.2019.1012093

Stewart, M., Olsen, G., Hickey, C. W., Ferreira, B., Jelić, A., Petrović, M., & Barcelo, D. (2014).A survey of emerging contaminants in the estuarine receiving environment around Auckland, New Zealand. Science of The Total Environment, 468-469, 202–210. Doi: https://doi.org/10.1016/j.scitotenv.2013.08.039:

van der Merwe, J., Steenekamp, J., Steyn, D. & Hamman, J. (2020). The Role of Functional Excipients in Solid Oral Dosage Forms to Overcome Poor Drug Dissolution and Bioavailability. Pharmaceutics, 12, 393. Doi: https://doi.org/10.3390/pharmaceutics12050393

Vaňková, M. (2010). Biodegradability analysis of pharmaceuticals used in developing countries; screening with OxiTop ® - C 11073f., Doctoral thesis. Tampere University of Applied Sciences, Finland

Verlicchi, P., Al Aukidy, M., & Zambello, E. (2012). Occurrence of pharmaceutical compounds in urban wastewater: removal, mass load and environmental risk after a secondary treatment - a review. Science of the total environment, 429, 123-155. Doi: https://doi.org/10.1016/j.scitotenv.2012.04.028

Wang, L., Wang, H., Chen, X., Zhuang, Y., Yu, Z. & Zhou, T. (2018). Acclimation process of cultivating Chlorella vulgaris in toxic excess sludge extract and its response mechanism. The Science of the total environment, 628-629, 858–869. Doi: https://doi.org/10.1016/j.scitotenv.2018.02.020

Weyman, G. S., Rufli, H., Weltje, L., Salinas, E. R. & Hamitou, M. (2012). Aquatic toxicity tests with substances that are poorly soluble in water and consequences for environmental risk assessment. Environmental toxicology and chemistry, 31: 1662–1669. Doi: https://doi.org/10.1002/etc.1856

Wood, T. P., Duvenage, C. S. J. & Rohwer, E. (2015). The occurrence of anti-retroviral compounds used for HIV treatment in South African surface water. Environmental pollution, 199: 235-243. Doi: https://doi.org/10.1016/j.envpol.2015.01.030

Zakrzewski, S. F. (2002). Environmental toxicology. Oxford University Press. ISBN-13: 9780195148114

Published

22/01/2022

How to Cite

DINIZ, J. S. .; FREITAS, L. A. de P. .; VAZ, I. C. D. .; BARBOSA, F. A. R. .; MOL, M. P. G. .; MAGALHÃES, S. M. S. .; SILVEIRA, M. R. . The toxic effects of the antiretroviral nevirapine and a nevirapine-based drug for aquatic organisms. Research, Society and Development, [S. l.], v. 11, n. 2, p. e19211225014, 2022. DOI: 10.33448/rsd-v11i2.25014. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/25014. Acesso em: 27 apr. 2024.

Issue

Section

Health Sciences