Browsing by Issue Date, starting with "2019-05-24"
Now showing 1 - 2 of 2
Results Per Page
Sort Options
- Environmental risk assessment and toxicity of pharmaceuticals in coastal tropical and temperate organismsPublication . Fonseca, Tainá; Bebianno, Maria JoãoDemographic attributes of the urban society have prompted a milestone shift towards structural aging of global population and increase of life expectancy, crucial to the prominence of cancer as one of the non-communicable diseases leading mortality. Currently, cancer diseases were accountable for about 9.6 million deaths in 2018, with concerning increasing projections of cancer incidence and mortality, by 2030, at a greater proportion in developing countries. As a result, there is an increasing trend of production and consumption of pharmaceuticals applied in cancer treatments. Once administered and metabolized, such drugs are excreted into waterways following to waste water treatment plants (WWTPs), ending up in freshwater and coastal ecosystems, where they can be found at a sub ng to ng L-1 range. Anticancer drugs are designed to damage DNA and disrupt mechanisms of its transcription, replication and synthesis, as well as suppress the cell´s defense, ultimately causing cell death. In cancer therapy, drugs are typically administered in a combinatory cocktail, that covers different molecular targets, reducing the risk of clonal selection based upon cell resistance to a single drug. However, these chemicals may bring potential toxicity if discharged into the aquatic environment, both in temperate and tropical zones, particularly in the benthic compartment, where they are expected to accumulate. In this sense, the present thesis aimed to assess the effects of anticancer agents of different classes, namely the cytotoxic platinum-based cisplatin (CisPt), the alkylating agent cyclophosphamide (CP) and the endocrine disruptor tamoxifen (TAM), on non-target benthic marine species under realistic environmental concentrations, at individual and combined exposures. For this purpose, a multi-biomarker approach was applied including the assessment of behavioural responses, oxidative stress, biotransformation, neurotoxicity, lipid peroxidation and genotoxicity in the temperate polychaete Nereis diversicolor, in addition to the evaluation of acute and chronic effects of drugs in tropical and representative benthic organisms: the sea urchin Echinometra lucunter, the polychaete Scolelepis squamata and the amphipod Tiburonella viscana from the Brazilian coast. The main results revealed that single drug exposures caused alteration of AChE activity, oxidative stress and oxidative damage and, ultimately, DNA damage in N. diversicolor. Besides, alterations in its burrowing behaviour also occurred, as an ecological outcome. These effects were more pronounced in organisms under CisPt at 100 ng Pt L-1, CP at 1000 ng L-1 and TAM at 0.5 ng L-1. Findings from bioassays with N. diversicolor conducted with drugs in tertiary mixtures indicated that each biomarker effect respond differently, according to the trends proposed by models of drugs´s interaction. Toxicity did not increase in a dose-response manner but showed different patterns of effects, in a way that the highest DNA damage was observed at the set of lowest concentrations (Mixture A), an absence of oxidative stress at the intermediary drug levels (Mix B and C), with a potential dominance of TAM´s MoA in organisms exposed to Mixture C and D, suggesting an antagonist interaction between the cytotoxic drugs. Therefore, the effects ruled by single-drug MoAs cannot provide estimations and protective measures for a prospective ERA regarding scenarios of their combination in the environment. Although evidence on estrogen receptors expression is still not disclosed for the herein selected biological models, determination of biochemical and genotoxic outcomes from TAM exposure are highlighted, since it is assumed to comprise a targeted therapy on nuclear estrogen receptors. Anticancer drugs´ concentrations that triggered the above-mentioned responses are potentially present in coastal environments, even more prone to be encountered in developing regions, where technologies of WWTPs are not efficient or are lacking. Accordingly, effects regarding the bioassays conducted with the tropical counterparts showed a non-monotonic reduction of viable pluteus larvae of E. lucunter, at CisPt and CP treatment respectively at the range from 0.1 to 10 ng Pt L-1, and from 50 to 500 ng CP L-1, in contrast to the increasing reduction of embryo larval development under TAM exposure, significant over the whole range of concentrations. In polychaetes S. squamata, a significant acute toxicity was exerted at the higher pharmaceutical doses (Mix C and D). In the amphipod T. viscana demonstrated a higher sensitivity to pharmaceuticals, presenting a significant non-linear reduction of survival in Mix B and D, as a potential outstanding effect of TAM when present as mixtures. By virtue of the non-monotonicity addressed in the dose-responses relationships reported in all bioassays, another concern stands out on the urgency to the development of a risk analysis and safety assessment designated to anticancer drugs.
- Implementação de um sistema de gestão da segurança alimentar (SGSA) numa associação de criadores de gado caprino: produção de queijo fresco e iogurtePublication . Drago, Vera Sofia Lima; Ratão, IsabelA garantia da segurança alimentar, pode ser alcançada através da adoção de medidas de controlo das atividades e dos processos, procedimentos e recursos, de acordo com os padrões que constituem a base para os Sistemas de Gestão de Segurança Alimentar (SGSA), como são os casos do sistema de análise de perigos e pontos críticos de controlo (HACCP). A metodologia HACCP é uma referência aceite e reconhecida internacionalmente para implementar sistemas de segurança alimentar considerados eficazes, sendo de aplicação obrigatória na União Europeia desde 2006. A implementação de um sistema de qualidade rigoroso e o desenvolvimento do sistema HACCP tem afetado positivamente a produção de laticínios. O sistema HACCP deve ser construído sobre uma base sólida constituída, por programas que incluam o cumprimento dos designados pré-requisitos, tais como os que estão no âmbito das boas práticas de fabrico e dos procedimentos de higiene. O objetivo desta dissertação foi desenvolver e implementar um SGSA, baseado no sistema HACCP, definido pelo Codex Alimentarius Commission, para as atividades de produção de queijo fresco e iogurte de cabra. Após a análise das etapas de produção do queijo fresco e do iogurte de cabra, concluiuse que o sistema de gestão da segurança alimentar, anteriormente implementado no estabelecimento em estudo, precisava de melhorias. Assim, procedeu-se à atualização do programa de pré-requisitos e do plano HACCP chegando-se à conclusão que, tanto a produção de queijo fresco como a de iogurte, apresentavam diversas etapas com perigos que têm de ser controlados e às quais deverão ser aplicadas medidas preventivas. Concluiu-se que as etapas receção do leite, do sal, do cardo, das ervas aromáticas, do leite em pó e dos fermentos lácteos e a pasteurização são pontos críticos de controlo neste processo tendo-se sugerido limites críticos e medidas corretivas para os perigos a eles associados. Para garantir esse controlo criaram-se procedimentos e fichas de registo.