Untitled

Funder

Organizational Unit

Publications

Analysis Of The Cytotoxicity And Genotoxicity of Digested Titanium Dioxide Nanomaterials (TiO2) In Intestinal Cells

Publication . Louro, Henriqueta; Vieira, Adriana; Gramacho, Ana Catarina; Rolo, Dora; Vital, Nádia; Martins, Carla; Assunção, Ricardo; Alvito, Paula; Gonçalves, Lídia; Bettencourt, Ana Francisca; Silva, Maria João

Titanium dioxide nanomaterials (TiO2) have been frequently applied as food additives, in pharmaceuticals and in personal care products, such as toothpastes. Despite some regulators like EFSA concluded that the absorption of orally administered TiO2 is low, and that the use of TiO2 as a food additive does not raise a genotoxic concern, the presence of TiO2 in human organs was recently reported. This exposure may lead to adverse outcomes and has been poorly investigated. Furthermore, many of the biological effects of TiO2 described in the literature often overlook adequate physicochemical properties and their modification due to NMs interaction with the surrounding physiological matrices happening, e.g, during digestion. This work aimed to investigate in intestinal cells, the cyto- and genotoxic effects of TiO2 after the simulation of the human digestive process using the standardized INFOGEST in vitro digestion method, to better understand their potential negative impacts on the gastrointestinal tract. The TiO2 were characterized before and after digestion using DLS, zeta potential and TEM-EDS. The digestion product was used for cytotoxicity (MTT) and genotoxicity (comet, micronucleus) assays in two types of intestinal cells (Caco-2 and mucus secreting HT29-MTX cells). The results of the cytotoxicity and genotoxicity assays are discussed in view of the TiO2 secondary characteristics, to further understand the potential adverse intestinal outcomes in light of the transformation they suffer during digestion.

2020-09-12Conference object

Restricted access

Mycotoxins under the Human Biomonitoring Initiative (HBM4EU): shedding light on the exposure of European citizens to Mycotoxins

Publication . Alvito, Paula; Assunção, Ricardo; Dirven, H.; Mol, H.; Martins, Carla; Mengelers, M.; Plitcha, V.; Vasco, Elsa; Viegas, S.; Silva, M.J.

The Human Biomonitoring Initiative HBM4EU (https://www.hbm4eu.eu/the-project/) is a joint effort of 30 countries and the European Environment Agency under the Horizon 2020 funding programme of the European Commission. The project started in 2017 and has a duration of five years. The goal of HBM4EU is to generate evidence on the current exposure of European citizens to chemicals and on their possible health effects in order to assess the associated risks. Further, this project should provide policy makers scientifically founded advice on chemical safety and human health protection. Following a systematic prioritization exercise, which brought together national and EU level policy needs for knowledge on chemical exposure and health outcomes, mycotoxins (Deoxynivalenol and Fumonisin B1) were in the 2nd prioritisation round considered as priority substances around which the HBM4EU research programme will be developed. Within the three pillars of the HBM4EU, namely, 1. Science to Policy, 2. European HBM (Human Biomonitoring) Platform and 3. Exposure and Health, answers to several identified policy questions related to mycotoxins exposure and effects will be debated, namely the current levels of human exposure (including exposure to mixtures) and time trends in Europe, geographical differences and highly exposed subgroups (including workers), the availability of toxicokinetics data, methods for analyzing mycotoxins and their metabolites in human samples, the potential for using effect biomarkers and their link to adverse outcomes, the use of biomonitoring data under a risk assessment framework and derivation of HBM guidance values. All these topics will be considered and explored, providing new evidences that will constitute important contributes for the mycotoxins risk assessment in the EU and abroad. Activities related to translation of exposure to policy (WP5), laboratory analysis and quality assurance (WP9), data management and analysis (WP10), from HBM to exposure (WP12), establishing exposure-health relationships (WP13), effect biomarkers (WP14) and mixtures and human health risk (WP15) will be developed within a joint effort of chemical group leaders for mycotoxins, members of the mycotoxin group at HBM4EU and different Work Package leaders . One of the most relevant planned activities is the possibility for providing new exposure data through the development of an aligned study enrolling several European countries. This will guarantee an update on the exposure assessment to the prioritized mycotoxins in the European population allowing a more accurate risk assessment.

2020-01Conference object

Restricted access

Dietary exposure to aflatoxins in the Portuguese population – the use of biomonitoring data to assess the associated burden

Publication . Martins, Carla; Vidal, Arnau; De Boevre, M.; De Saeger, Sarah; Nunes, Carla; Torres, Duarte; Goios, Ana; Lopes, Carla; Alvito, Paula; Assunção, Ricardo

Background: Human biomonitoring (HBM) is an important tool to assess the human exposure to chemicals, contributing to describe trends of exposure over time and to identify population groups that could be under risk. Aflatoxins (AFTs) are genotoxic and carcinogenic compounds causing hepatocellular carcinoma (HCC), the third leading cause of cancer deaths worldwide. In Portugal, scarce data are available regarding exposure to AFTs and none previous study used HBM data to characterize comprehensively the associated burden. Methods: 24h-urine samples (n=94) were analyzed by liquid chromatography–mass spectrometry (LC-MS/MS) for the determination of AFTs (B1, B2, G1, G2, M1). Regarding left-censored data (< LOD) a substitution approach was considered (< LOD = 0). Deterministic and probabilistic models were developed to estimate the health impact of the exposure to aflatoxins, estimating the DALYs attributed to AFTs exposure for the Portuguese population (10291k). Results: AFTs were detected in 13% (AFB1), 16% (AFB2), 1% (AFG1), 2% (AFG2) and 19% (AFM1) of the 24h-urine samples. The mean probable daily intake estimated was 16.7 and 13.4 ng/kg body weight/day, calculated mean DALYs/100k were 1.7 (0-10.7) and 1.68 (0.04-6.23) considering the deterministic and probabilistic models, respectively. Conclusion: The present study generated, for the first time and within a HBM study, reliable and crucial data to characterize the burden associated to Portuguese population exposure to aflatoxins. The obtained results constitute an important contribution to support risk managers in the establishment of preventive policy measures that contribute to ensure the public health protection.

2020-02Conference object

Restricted access

Exposição da população portuguesa a micotoxinas: o contributo da biomonitorização humana

Publication . Martins, Carla; Vidal, Arnau; De Boevre, Marthe; De Saeger, Sarah; Nunes, Carla; Torres, Duarte; Goios, Ana; Lopes, Carla; Assunção, Ricardo; Alvito, Paula

As micotoxinas constituem um grupo de contaminantes alimentares que poderão provocar vários efeitos tóxicos na saúde humana, entre eles efeitos estrogénicos, imunotóxicos, nefrotóxicos e teratogénicos. É por isso importante avaliar a exposição humana a estes compostos, através da análise direta dos seus biomarcadores em amostras biológicas. Em Portugal existem poucos dados disponíveis de exposição a micotoxinas obtidos em estudos de biomonitorização humana. Face a esta ausência de informação, o presente estudo teve como objetivo determinar os biomarcadores de exposição a micotoxinas em amostras de urina de 24 horas, colhidas no âmbito do Inquérito Nacional de Alimentação, Nutrição e Atividade Física da População Geral Portuguesa (2015-2016), e avaliar o risco associado a esta exposição. A determinação analítica destes compostos foi efetuada por cromatografia líquida com deteção por espectrometria de massa permitindo a deteção e quantificação simultânea de 37 biomarcadores de exposição a micotoxinas presentes na urina. Os dados obtidos foram utilizados para estimar a Ingestão Diária Provável e caracterizar o risco através da determinação do Quociente de Perigo. Os resultados obtidos revelaram a exposição da população portuguesa a zearalenona, desoxinivalenol, ocratoxina A, alternariol, citrinina e fumonisina B1. Os dados de caracterização de risco revelaram uma potencial preocupação, considerando que os valores de referência de ingestão foram excedidos em alguns participantes. A micotoxina alternariol foi identificada e quantificada, pela primeira vez, em amostras de urina num país europeu; no entanto, a caracterização do risco não foi efetuada dado não existir um valor de referência estabelecido internacionalmente. Estes resultados confirmam que a população Portuguesa está exposta a micotoxinas, reforçando a necessidade de mais estudos sobre os determinantes desta exposição.

2019-12Journal article

Open access

Risks versus benefits of nuts’ consumption in Portugal: the balance between preventable myocardial infarction and the risk of liver cancer associated to aflatoxin exposure

Publication . Assunção, Ricardo; Lea, S.; Alvito, Paula; Carmona, P.; Carvalho, C.; Lopes, C.; Martins, Carla; Monteiro, Sarogini; Nabais, P.; Oliveira, D.; Torres, D.; Viegas, C.; Viegas, S.; Nauta, Maarten; Pires, S.

The occurrence of mycotoxins in nuts, including the most potent carcinogenic aflatoxins (AFTs), has been reported by several authors worldwide. Notwithstanding, nut consumption plays an important role in the Mediterranean diet due to their nutrient contents and the consequent potential to produce beneficial health effects, as the prevention of cardiovascular diseases (CVD). Any measure that could contribute to improve this indicator should be accurately evaluated. According to the National Food, Nutrition and Physical Activity Survey (IAN-AF 2015-16), the current adults’ mean nut consumption in Portugal is 2.7 g/day. Some recent epidemiological studies (e.g. PREDIMED) suggested that a daily nuts consumption of 30 g could reduce the incidence of CVD. The present study aimed to quantify the health impact in terms of Disability-adjusted life years (DALY) of increasing nut consumption to 30 g/day by adult Portuguese population, when compared to the current intake. Regarding nut consumption, two scenarios were established: current consumption (CS) – 2.7 g/day; alternative scenario (AS) – 30 g/day. AFTs occurrence in nuts available in Portuguese market and nut consumption data were used to estimate AFTs intake. Epidemiological and National population data were used to estimate the DALYs, considering two different endpoints: the occurrence of hepatocellular carcinoma due to exposure to AFTs (IPSC/WHO) and the prevention of acute myocardial infarction due to nuts’ consumption (PREDIMED). A mean daily intake of AFTs of 0.035 (CS) and 0.393 (AS) ng/kg bw/day was predicted. This intake is estimated to cause 0.04 (CS) and 0.40 (AS) extra cases of Hepatocellular Carcinoma, corresponding to 0.7 (CS) and 7.5 (AS) annual DALYs. In contrast, the estimated number of preventable cases of myocardial infarction due to the increasing of nut consumption to 30 g/day was 3361 and the DALYs gained was 4188. Integrating risks and benefits, 4181 annual DALYs could be potentially saved. These results suggest an overall beneficial health effect of increased nut consumption in Portugal. Therefore, it seems not advisable to reduce exposure to AFTs by recommending a reduced intake of nuts.

2019-05Conference object

Restricted access