Browsing by Issue Date, starting with "2015-09-14"
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- Moving towards a safe by design approach for ENM: linking ENM relevant properties to toxicological concernsPublication . Borges, Teresa; Silva, Maria João; Louro, HenriquetaWithin the Safe by Design concept, the functionality of a material and its toxicity are considered in an integrated way. The central goal of this presentation is to discuss some fundamental principles of engineered nanomaterials (ENM) interactions with biological systems relevant to human exposure and biological responses. Major factors to consider in the ENM safe-by-design approach are surface modification to reduce the potential hazardous properties of target nanoparticles (NP), compatibility between NP coatings and their matrix, as well as biopersistence, considering the relevant exposure scenarios across the life cycle of the target NP and products. This is a cross-disciplinary field that needs to identify, at earlier stages of the ENM R&D process, the physicochemical properties that may act as good predictors of toxicity, e.g. crystal structure/reactivity, zeta potential/surface charge/dynamic properties. Furthermore, it is also needed to build adequate screening in vitro testing strategies (realistic doses, exposure duration and target tissues), incorporating relevant hazard endpoints that can give an insight about the toxicological mode of action (MoA) with relevance to human health and environment, taking into account the uses and applications along the lifecycle (EHS roadmap). These topics will be illustrated by a cytotoxicity and genotoxicity study performed with a set of ENM with identical chemistry but different physicochemical characteristics that highlighted the importance of investigating each ENM individually, instead of assuming a common MoA. The findings, although creating a dilemma for developing criteria for categorization and read-across, are also suggestive of the importance of considering the functionality of a material and its toxicity in an integrated way, enabling a safe-by-design concept. Ultimately, the overall safety data is intended to best support the decision of IND developers and risk managers during the ENM design and development processes.
- A contribution to hazard assessment of combined exposure to mycotoxins using in vitro toxicity testingPublication . Tavares, Ana; Pinhão, Mariana; Mendonça, Inês; Louro, Henriqueta; Loureiro, Susana; Alvito, Paula; Silva, Maria JoãoHumans may be exposed through diet to a complex and variable combination of mycotoxins co-occurring in food. These toxins may impact on their health, particularly on the long-term, because most of them are mutagenic and carcinogenic (e.g., aflatoxin B1). Moreover, the overall hazard of a particular mycotoxin may be further modified by its interaction with other mycotoxins and, in this context, many data gaps still remain. To overcome this issue, EFSA has recommended the use of concentration addition (CA) as a default assumption for the assessment of combined toxicity of chemicals, provided they produce a common adverse outcome. The present study aimed at identifying potential interactive toxic effects of two binary mixtures of mycotoxins – ochratoxin A (OTA)/aflatoxin M1 (AFM1) and OTA/fumonisin B1 (FB1) – in human cell lines. Cytotoxic effects were measured by the neutral red or the MTT assays while genotoxicity was assessed by the comet assay. Comparison of the viability results obtained for OTA in intestinal (Caco-2), liver (HepG2) and kidney (HK-2) cell lines showed that HK-2 cells were the most sensitive ones. On the other hand, the highest doses of AFM1 exerted a significant toxicity in Caco-2 cells, while FB1 displayed a lower toxic effect in HepG2 and HK-2 cells. The interactive toxic effects of several combinations of AFM1 and OTA were inferred from modelling the experimental data obtained for mixtures, comparatively to that expected from the individual effects, using a CA conceptual model. The results indicated that both mycotoxins exerted antagonistic effects in Caco-2 cells. In contrast, in HK-2 cells the combination of OTA and FB1 was synergistic at low dose levels of both mycotoxins and changed to antagonism at higher dose levels. Genotoxicity analysis of the same combinations is underway and data will be presented and discussed. Overall, this study emphasizes the relevance of assessing the combined toxicity of mycotoxins, thereby contributing to fill the data gaps on mixtures effects and allowing the development of qualitative/semi-quantitative or probabilistic models for the hazard assessment of combined exposure to these food contaminants.