Assessing the impacts of cytostatic drugs on freshwater biota
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10773/30682 |
Resumo: | Cytostatic drugs are a class of pharmaceuticals used for cancer treatment, whose incidence has been increasing. These drugs are excreted mainly via urine subsequently reaching wastewater treatment plants (WWTPs). However, WWPTs do not always possess the proper means to effectively eliminate these drugs, meaning that they continuously enter the environment where they might reach surface and drinking waters. Since most anticancer drugs possess carcinogenic, teratogenic, genotoxic, and mutagenic properties, they might pose a potential risk to environmental and human health. In this context, the present work aimed at assessing the ecotoxicity of three cytostatic drugs (cyclophosphamide - CYP, mycophenolate mofetil - MMF, and mycophenolic acid - MPA) on freshwater species representing different trophic levels and functional groups: the microalga Raphidocelis subcapitata, the rotifer Brachionus calyciflorus, and the fish Danio rerio. The following endpoints were monitored: yield and population growth rates for the alga after an exposure of 72h; mortality for the rotifer after an exposure of 24h, and mortality, hatching rates, and morphological abnormalities, for the fish after an exposure of 96h. Regarding the assays with the microalga, it was not possible to determine the values for the endpoints evaluated for MMF and MPA. However, for CYP an EC50,72h of 593.0 mg L-1 for biomass inhibition and an EC50,72h of 1108 mg L-1 for growth inhibition were determined. For rotifers, LC50,24h values could not be computed for MMF and MPA, since at the highest tested concentration (40 and 30 mg L-1 , respectively - corresponding to the solubility limits of the compounds) no mortality was observed. Though an LC50,24h of 6397 mg L-1 for CYP was determined. Overall, MMF and MPA proved to be the most toxic compounds for zebrafish assays, with LC50,96h values of 0.046 and 1.410 mg L-1 , respectively, against an LC50,96h of 1306 mg L-1 for CYP. All cytostatics caused morphological abnormalities on zebrafish embryos, that mainly included oedemas and spinal cord malformations. Based on these results, the predicted no effects concentrations (PNEC) were derived for each compound to calculate the risk quotient (RQ), that relates toxicity to environmental exposure. The predicted or measured environmental concentrations in superficial waters were retrieved from the literature. In general, CYP revealed a low risk for freshwater biota (RQ = 0.003), while MMF and MPA presented RQ values above 1 (RQ = 3.0 and 4.1, respectively), indicating a high risk to freshwater organisms. |
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Assessing the impacts of cytostatic drugs on freshwater biotaEnvironmental risk assessmentPharmaceuticalsEcotoxicologyAquatic contaminationCytostatic drugs are a class of pharmaceuticals used for cancer treatment, whose incidence has been increasing. These drugs are excreted mainly via urine subsequently reaching wastewater treatment plants (WWTPs). However, WWPTs do not always possess the proper means to effectively eliminate these drugs, meaning that they continuously enter the environment where they might reach surface and drinking waters. Since most anticancer drugs possess carcinogenic, teratogenic, genotoxic, and mutagenic properties, they might pose a potential risk to environmental and human health. In this context, the present work aimed at assessing the ecotoxicity of three cytostatic drugs (cyclophosphamide - CYP, mycophenolate mofetil - MMF, and mycophenolic acid - MPA) on freshwater species representing different trophic levels and functional groups: the microalga Raphidocelis subcapitata, the rotifer Brachionus calyciflorus, and the fish Danio rerio. The following endpoints were monitored: yield and population growth rates for the alga after an exposure of 72h; mortality for the rotifer after an exposure of 24h, and mortality, hatching rates, and morphological abnormalities, for the fish after an exposure of 96h. Regarding the assays with the microalga, it was not possible to determine the values for the endpoints evaluated for MMF and MPA. However, for CYP an EC50,72h of 593.0 mg L-1 for biomass inhibition and an EC50,72h of 1108 mg L-1 for growth inhibition were determined. For rotifers, LC50,24h values could not be computed for MMF and MPA, since at the highest tested concentration (40 and 30 mg L-1 , respectively - corresponding to the solubility limits of the compounds) no mortality was observed. Though an LC50,24h of 6397 mg L-1 for CYP was determined. Overall, MMF and MPA proved to be the most toxic compounds for zebrafish assays, with LC50,96h values of 0.046 and 1.410 mg L-1 , respectively, against an LC50,96h of 1306 mg L-1 for CYP. All cytostatics caused morphological abnormalities on zebrafish embryos, that mainly included oedemas and spinal cord malformations. Based on these results, the predicted no effects concentrations (PNEC) were derived for each compound to calculate the risk quotient (RQ), that relates toxicity to environmental exposure. The predicted or measured environmental concentrations in superficial waters were retrieved from the literature. In general, CYP revealed a low risk for freshwater biota (RQ = 0.003), while MMF and MPA presented RQ values above 1 (RQ = 3.0 and 4.1, respectively), indicating a high risk to freshwater organisms.Os citostáticos são uma classe de fármacos usados no tratamento do cancro, cuja incidência tem vindo a aumentar. Estes fármacos são excretados principalmente através da urina chegando, posteriormente, às estações de tratamento de águas residuais (ETARs). Contudo, as ETARs nem sempre possuem os meios adequados para conseguirem eliminar eficazmente estes fármacos, o que significa que eles entram de forma contínua no meio ambiente, podendo atingir águas superficiais e reservas de água potável. Uma vez que estes fármacos anticancerígenos possuem propriedades teratogénicas, carcinogénicas, genotóxicas e mutagénicas, eles podem apresentar um potencial risco para o ambiente e para a saúde humana. Neste contexto, o presente trabalho visou avaliar a ecotoxicidade de 3 citostáticos (ciclofosfamida - CYP, micofenolato de mofetil – MMF, e ácido micofenólico – MPA), em três espécies de água doce representativas de níveis tróficos e grupos funcionais diferentes: a microalga Raphidocelis subcapitata, o rotífero Brachionus calyciflorus, e o peixe Danio rerio. Os seguintes parâmetros biológicos foram avaliados: as taxas de biomassa e de crescimento populacional para a microalga após 72 horas de exposição; a mortalidade para o rotífero após 24 horas de exposição; as taxas de mortalidade e eclosão, e percentagem de deformações morfológicas para o peixe-zebra após 96 horas de exposição. Relativamente aos ensaios com a microalga, não foi possível determinar valores para os parâmetros biológicos avaliados para os compostos MMF e MPA. Já para a CYP foi possível determinar um EC50,72h de 593.0 mg L -1 para inibição da biomassa e um EC50,72h de 1108 mg L-1 para a inibição do crescimento. Para os rotíferos, os valores de LC50,24h para o MMF e MPA não puderam ser calculados, uma vez que às concentrações mais elevadas testadas (40 e 30 mg L-1 , respetivamente – correspondendo aos limites de solubilidade dos compostos) não foi observada mortalidade. Contudo, para a CYP foi determinado um LC50,24h de 6397 mg L-1 . No geral, o MMF e o MPA provaram ser os compostos mais tóxicos nos ensaios com o peixe-zebra, com valores de LC50,96h de 0.046 e 1.410 mg L-1 , respetivamente, contra um LC50,96h de 1306 mg L-1 para a CYP. Todos os citostáticos causaram deformidades morfológicas nos embriões de peixezebra, que incluíam principalmente edemas e malformações da medula espinal. Com base nestes resultados, as concentrações sem efeito previstas (predicted no-effect concentrations - PNEC) foram derivadas para cada composto para calcular o quociente de risco (RQ), que relaciona a toxicidade com os níveis de exposição ambiental. As concentrações ambientais previstas ou medidas em águas superficiais foram adquiridas da literatura. No geral, a CYP não apresentou risco para a biota de água doce (RQ = 0.003), enquanto o MMF e MPA apresentaram valores de RQ acima de 1 (3.0 e 4.1; respetivamente), representando um elevado risco para organismos dulçaquícolas.2023-01-28T00:00:00Z2021-01-28T00:00:00Z2021-01-28info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/30682engMonteiro, Bruna Ariana Ribeiroinfo:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-05-06T04:30:25Zoai:ria.ua.pt:10773/30682Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-05-06T04:30:25Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Assessing the impacts of cytostatic drugs on freshwater biota |
title |
Assessing the impacts of cytostatic drugs on freshwater biota |
spellingShingle |
Assessing the impacts of cytostatic drugs on freshwater biota Monteiro, Bruna Ariana Ribeiro Environmental risk assessment Pharmaceuticals Ecotoxicology Aquatic contamination |
title_short |
Assessing the impacts of cytostatic drugs on freshwater biota |
title_full |
Assessing the impacts of cytostatic drugs on freshwater biota |
title_fullStr |
Assessing the impacts of cytostatic drugs on freshwater biota |
title_full_unstemmed |
Assessing the impacts of cytostatic drugs on freshwater biota |
title_sort |
Assessing the impacts of cytostatic drugs on freshwater biota |
author |
Monteiro, Bruna Ariana Ribeiro |
author_facet |
Monteiro, Bruna Ariana Ribeiro |
author_role |
author |
dc.contributor.author.fl_str_mv |
Monteiro, Bruna Ariana Ribeiro |
dc.subject.por.fl_str_mv |
Environmental risk assessment Pharmaceuticals Ecotoxicology Aquatic contamination |
topic |
Environmental risk assessment Pharmaceuticals Ecotoxicology Aquatic contamination |
description |
Cytostatic drugs are a class of pharmaceuticals used for cancer treatment, whose incidence has been increasing. These drugs are excreted mainly via urine subsequently reaching wastewater treatment plants (WWTPs). However, WWPTs do not always possess the proper means to effectively eliminate these drugs, meaning that they continuously enter the environment where they might reach surface and drinking waters. Since most anticancer drugs possess carcinogenic, teratogenic, genotoxic, and mutagenic properties, they might pose a potential risk to environmental and human health. In this context, the present work aimed at assessing the ecotoxicity of three cytostatic drugs (cyclophosphamide - CYP, mycophenolate mofetil - MMF, and mycophenolic acid - MPA) on freshwater species representing different trophic levels and functional groups: the microalga Raphidocelis subcapitata, the rotifer Brachionus calyciflorus, and the fish Danio rerio. The following endpoints were monitored: yield and population growth rates for the alga after an exposure of 72h; mortality for the rotifer after an exposure of 24h, and mortality, hatching rates, and morphological abnormalities, for the fish after an exposure of 96h. Regarding the assays with the microalga, it was not possible to determine the values for the endpoints evaluated for MMF and MPA. However, for CYP an EC50,72h of 593.0 mg L-1 for biomass inhibition and an EC50,72h of 1108 mg L-1 for growth inhibition were determined. For rotifers, LC50,24h values could not be computed for MMF and MPA, since at the highest tested concentration (40 and 30 mg L-1 , respectively - corresponding to the solubility limits of the compounds) no mortality was observed. Though an LC50,24h of 6397 mg L-1 for CYP was determined. Overall, MMF and MPA proved to be the most toxic compounds for zebrafish assays, with LC50,96h values of 0.046 and 1.410 mg L-1 , respectively, against an LC50,96h of 1306 mg L-1 for CYP. All cytostatics caused morphological abnormalities on zebrafish embryos, that mainly included oedemas and spinal cord malformations. Based on these results, the predicted no effects concentrations (PNEC) were derived for each compound to calculate the risk quotient (RQ), that relates toxicity to environmental exposure. The predicted or measured environmental concentrations in superficial waters were retrieved from the literature. In general, CYP revealed a low risk for freshwater biota (RQ = 0.003), while MMF and MPA presented RQ values above 1 (RQ = 3.0 and 4.1, respectively), indicating a high risk to freshwater organisms. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-01-28T00:00:00Z 2021-01-28 2023-01-28T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10773/30682 |
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http://hdl.handle.net/10773/30682 |
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eng |
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eng |
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info:eu-repo/semantics/embargoedAccess |
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embargoedAccess |
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application/pdf |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
mluisa.alvim@gmail.com |
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1817543770207420416 |