Browsing by Author "Vidal, Arnau"
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- Burden of disease associated with dietary exposure to carcinogenic aflatoxins in Portugal using human biomonitoring approachPublication . Martins, Carla; Vidal, Arnau; De Boevre, M.; De Saeger, Sarah; Nunes, Carla; Torres, Duarte; Goios, A.; Lopes, Carla; Alvito, Paula; Assunção, RicardoHuman biomonitoring is an important tool to assess human exposure to chemicals, contributing to describe trends of exposure over time and to identify population groups that could be under risk. Aflatoxins are genotoxic and carcinogenic food contaminants causing hepatocellular carcinoma, the third leading cause of cancer deaths worldwide. In Portugal, scarce data are available regarding exposure to aflatoxins and no previous study used human biomonitoring data to comprehensively characterize the associated burden of disease. 24 h urine and first-morning urine paired samples were collected by 94 participants and were analyzed by liquid chromatography–tandem mass spectrometry for the quantitative determination of aflatoxins (B1, B2, G1, G2 and M1). Deterministic and probabilistic models were developed to assess the Portuguese exposure to aflatoxins and to estimate the health impact of this exposure, estimating the attributed Disability-Adjusted Life Years (DALYs). Aflatoxins were detected in a maximum of 13% (AFB1), 16% (AFB2), 1% (AFG1), 2% (AFG2) and 19% (AFM1) of the urine samples. Data obtained through the probabilistic approach revealed an estimated mean probable daily intake of 13.43 ng/kg body weight per day resulting in 0.13 extra cases of hepatocellular carcinoma, corresponding to mean annual DALYs of 172.8 for the Portuguese population (10 291 027 inhabitants). The present study generated for the first time and within a human biomonitoring study, reliable and crucial data to characterize the burden associated to the exposure to aflatoxins of the Portuguese population. The obtained results constitute an imperative support to risk managers in the establishment of preventive policy measures that contribute to ensure public health protection.
- Burden of disease attributable to exposure to aflatoxins in PortugalPublication . Martins, Carla; Vidal, Arnau; De Boevre, M.; De Saeger, Sarah; Nunes, Carla; Torres, D.; Goios, A.; Lopes, Carla; Alvito, Paula; Assunção, RicardoHuman biomonitoring (HBM) is recognized as an important tool to assess the Human exposure to chemicals, contributing to describe trends and patterns of exposure over time and to identify population groups that could be under risk. Natural chemicals as mycotoxins, fungi metabolites that produce toxic effects in humans, are important compounds that could be found in foods usually consumed worldwide in a daily basis. Mycotoxins as aflatoxins (AFTs) are genotoxic, carcinogenic and immunosuppressive compounds. Hepatocellular carcinoma (HCC) is one of their main health toxic effects and is 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 burden associated to this exposure. In the scope of the National Food, Nutrition, and Physical Activity Survey of the Portuguese General Population (2015-2016), 24h-urine samples from 94 participants were analyzed by liquid chromatography–mass spectrometry (LC-MS/MS) for the simultaneous determination of AFTs (B1, B2, G1, G2, M1). A model was developed to estimate the health impact of the exposure of Portuguese population to aflatoxins, estimating the number of cases of HCC and DALYs attributed to AFTs exposure. AFTs were detected in 12.8% (AFB1), 16.0% (AFB2) and 19.1% (AFM1) of the 24h-urine samples. The estimated number of extra cases of HCC attributed to this exposure ranged from 17 to 65 cases/year; the associated DALYs for the Portuguese population ranged from 284 to 1802 years. The present study generated, for the first time and within a HBM study, reliable data regarding the exposure of the Portuguese population to AFTs. These data were crucial to characterize the health impact associated to AFTs exposure and to support risk managers to establish preventive policy measures that contribute to ensure the public health protection. Main messages: Portuguese population is exposed to aflatoxins, chemical food contaminants that may be harmful (carcinogenic, immunotoxic, mutagenic, teratogenic, hepatotoxic) to humans. Human biomonitoring studies provide realistic data on internal exposure at individual level, contributing to a more accurate estimation of the burden derived from this exposure.
- Deoxynivalenol exposure assessment through a modelling approach of food intake and biomonitoring data – A contribution to the risk assessment of an enteropathogenic mycotoxinPublication . Martins, Carla; Torres, Duarte; Lopes, Carla; Correia, Daniela; Goios, Ana; Assunção, Ricardo; Alvito, Paula; Vidal, Arnau; De Boevre, Marthe; De Saeger, Sarah; Nunes, CarlaDeoxynivalenol (DON), an enteropathogenic mycotoxin produced by Fusarium species, is usually associated with adverse health outcomes such as gastrointestinal diseases and immunotoxicity. To estimate DON exposure of the Portuguese population at national level, a modelling approach, based on data from 94 Portuguese volunteers, was developed considering the inputs of the food consumption data generated within the National Food and Physical Activity Survey and the human biomonitoring data used to assess the exposure to DON. Ten models of association between DON urinary biomarkers and food items (pasta, cookies, biscuits, sweets, bread, rusks, nuts, oilseeds, beer, meat, milk) were established. Applying the most adequate model to the consumption data (n = 5811) of the general population, the exposure estimates of the Probable Daily Intake revealed that a fraction (0.1%) of the Portuguese population might exceed the Tolerable Daily Intake defined for DON. The analysis stratified by age revealed children (3.2%) and adolescents (6.0%) are more likely to exceed the Tolerable Daily Intake for DON. Although the unavoidable uncertainties, these results are important contributions to understand the exposure to this mycotoxin in Portugal, to assess the associated risk and the potential public health consequences.
- Dietary exposure to aflatoxins in the Portuguese population – the use of biomonitoring data to assess the associated burdenPublication . Martins, Carla; Vidal, Arnau; De Boevre, M.; De Saeger, Sarah; Nunes, Carla; Torres, Duarte; Goios, Ana; Lopes, Carla; Alvito, Paula; Assunção, RicardoBackground: 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.
- earlyMYCO: A Pilot Mother-Child Cohort Study to Assess Early-Life Exposure to Mycotoxins - Challenges and Lessons LearnedPublication . Martins, Carla; Assunção, Ricardo; Costa, Ana; Serrano, Débora; Visintin, Lia; De Boevre, Marthe; Lachat, Carl; Vidal, Arnau; De Saeger, Sarah; Namorado, Sónia; Vidigal, Cristina; Almeida, Elisabete; Alvito, Paula; Nunes, CarlaEarly-life exposure occurs during gestation through transfer to the fetus and later, during lactation. Recent monitoring data revealed that the Portuguese population is exposed to mycotoxins, including young children. This study aimed to develop a pilot study to assess the early-life exposure to mycotoxins through a mother-child cohort, and to identify the associated challenges. Participants were recruited during pregnancy (1st trimester) and followed-up in three moments of observation: 2nd trimester of pregnancy (mother), and 1st and 6th month of the child's life (mother and child), with the collection of biological samples and sociodemographic and food consumption data. The earlyMYCO pilot study enrolled 19 mother-child pairs. The analysis of biological samples from participants revealed the presence of 4 out of 15 and 5 out of 18 mycotoxins' biomarkers of exposure in urine and breast milk samples, respectively. The main aspects identified as contributors for the successful development of the cohort were the multidisciplinary and dedicated team members in healthcare units, reduced burden of participation, and the availability of healthcare units for the implementation of the fieldwork. Challenges faced, lessons learned, and suggestions were discussed as a contribution for the development of further studies in this area.
- Exposição da população portuguesa a micotoxinas: o contributo da biomonitorização humanaPublication . Martins, Carla; Vidal, Arnau; De Boevre, Marthe; De Saeger, Sarah; Nunes, Carla; Torres, Duarte; Goios, Ana; Lopes, Carla; Assunção, Ricardo; Alvito, PaulaAs 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.
- Exposure of Portuguese population to aflatoxins: the contribution of human biomonitoring to estimation of burden of diseasePublication . Martins, Carla; Vidal, Arnau; De Boevre, M.; De Saeger, S.; Nunes, Carla; Torres, D.; Goios, A.; Lopes, C.; Alvito, Paula; Assunção, RicardoHuman biomonitoring (HBM) is recognized as an important tool to assess the Human exposure to chemicals, contributing to describe trends and patterns of exposure over time and to identify population groups that could be under risk. Natural chemicals as mycotoxins, fungi metabolites that produce toxic effects in humans, are important compounds that could be found in foods usually consumed worldwide in a daily basis. Mycotoxins as aflatoxins (AFTs) are genotoxic, carcinogenic and immunosuppressive compounds. Hepatocellular carcinoma (HCC) is one of their main health toxic effects and is 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 burden associated to this exposure. In the scope of the National Food, Nutrition, and Physical Activity Survey of the Portuguese General Population (2015-2016), 24h-urine samples from 94 participants were analyzed by liquid chromatography–mass spectrometry (LC-MS/MS) for the simultaneous determination of AFTs (B1, B2, G1, G2, M1). A model was developed to estimate the health impact of the exposure of Portuguese population to aflatoxins, estimating the number of cases of HCC and DALYs attributed to AFTs exposure. AFTs were detected in 12.8% (AFB1), 16.0% (AFB2) and 19.1% (AFM1) of the 24h-urine samples. The estimated number of extra cases of HCC attributed to this exposure ranged from 17 to 65 cases/year; the associated DALYs for the Portuguese population ranged from 284 to 1802 years. The present study generated, for the first time and within a HBM study, reliable data on internal exposure to AFTs at individual level for the Portuguese population. These data were crucial to characterize the burden derived from this exposure and to support risk managers to establish preventive policy measures that contribute to ensure the public health protection.
- Exposure of Portuguese population to mycoestrogens: a public health concern?Publication . Martins, Carla; Vidal, Arnau; De Saeger, Sarah; Nunes, Carla; Torres, D.; Goios, A.; Lopes, C.; Assunção, Ricardo; Alvito, Paula; De Boevre, M.Alternariol (AOH) and zearalenone (ZEN) are mycotoxins that occur widely in food commodities, with particular incidence in cereals [1,2]. Both mycotoxins present estrogenic effects, therefore, it is crucial to assess the human exposure and the associated risk [2,3]. To date, there is a lack of human studies to assess exposure to ZEN and AOH through biomarkers analysis in Portugal. In the scope of the National Food, Nutrition, and Physical Activity Survey of the Portuguese General Population (IAN-AF, 2015-2016), 94 participants collected 24h-urine samples [4]. Following a salt-assisted matrix extraction, urine samples were analyzed by liquid chromatography–mass spectrometry (LC-MS/MS) for the simultaneous determination of ZEN, α-zearalenol (α-ZEL), β -zearalenol (β-ZEL), α-zearalanol (α-ZAL), β-zearalanol (β-ZAL), zearalanone (ZAN), zearalenone-14-glucoside (ZEN-14-GlcA), α-zearalenol-glucoside (α-ZEL-GlcA), β-zearalenolglucoside (β-ZEL-GlcA), zearalenone-14-sulfate (ZEN-14-Sulf), alternariol monomethyl ether (AME) and AOH. Risk characterization was performed using the Hazard Quotient (HQ) approach. ZEN, ZEN-14-GlcA and AOH were detected in 48%, 16% and 29% of analyzed samples, respectively, and median levels were 0.17 μg/L for ZEN and ZEN-14-GlcA and 0.28 μg/L for AOH. Participants were exposed to ZEN (n=35), AOH (n=15) and some volunteers showed co-exposure to both mycotoxins (n=12). Risk characterization of exposure to ZEN was performed and 24% of participants presented a HQ > 1, thus exceeding the Tolerable Daily Intake (TDI) of 0.250 μg/kg bw/day. There is no toxicological data available to support the establishment of a TDI for AOH, thus the risk associated with this toxin was not characterized [2,5]. The present study generated, for the first time and within a human biomonitoring study, reliable data regarding the exposure of the Portuguese population to ZEN and AOH. These data are crucial to perform a more realistic risk assessment, contributing to more effective preventive measures for health protection of the Portuguese population.
- Is Portuguese population exposed to Zearalenone? A human biomonitoring study as a contribution to the risk assessment of an endocrine disruptorPublication . Martins, Carla; Vidal, Arnau; De Saeger, S.; Assunção, R.; Nunes, Carla; Torres, D.; Goios, A.; Lopes, Carla; Alvito, Paula; De Boevre, MartheZearalenone (ZEN) is a mycotoxin that occurs widely in food commodities with particular incidence in cereals. Due to chemical structures similar to the endogenous oestrogen 17-β-estradiol, ZEN and its metabolites exert estrogenic toxicity. Therefore, it is crucial to assess ZEN exposure among the population and biomarker-driven research is a promising method to assess the human exposure. For this reason, ZEN metabolites such as α-zearalenol (α-ZEL), β-zearalenol (β-ZEL), α-zearalenal (α-ZAL), β-zearalenal (β-ZAL), zearalanone (ZAN) (phase I) and the glucuronides ZEN14GlcA, α-ZEL14GlcA and β-ZEL14Glc (phase II) were identified in biological fluids. With a potency factor of 60 relative to ZEN, α-ZEL is the most relevant metabolite in terms of human health. ZEN is characterized by a fast metabolism and excretion, therefore urine is the matrix commonly used to assess the exposure to this mycotoxin and its metabolites. To date, in Portugal, there is a lack of human studies to assess biomarkers of exposure to ZEN. Within the Scope of National Food, Nutrition, and Physical Activity Survey of the Portuguese General Population (2015-2016), 24h-urine samples and non-consecutive dietary assessments (two 24-hour recalls, 8-15 days apart) from 94 participants were included in the present study. Following a salt-assisted matrix extraction, urine samples were analyzed using LC-MS/MS for the simultaneous determination of ZEN, α-ZEL, β-ZEL, α-ZAL, β-ZAL, ZAN and ZEN14GlcA. ZEN and ZEN-14-GlcA were detected in 52% (36/69) and 14% (10/69) of the analyzed samples, with a mean concentration of 1.2 and 6.9 µg/L, respectively. The metabolites α-ZEL, β-ZEL, α-ZAL, β-ZAL, ZAN were not detected in the urine samples. Considering the 24h-urinary volume, the mean dietary excretion of ZEN and ZEN-14-GlcA was 1.5 and 7.8 µg/day, respectively. These data will allow the determination of Probably Daily Intake of zearalenone with more accuracy since it reflects the internal exposure of participants. The present biomonitoring study generates reliable data regarding the exposure of the Portuguese population to ZEN. These data are crucial to perform a more realistic risk assessment, contributing to the knowledge of determinants of this exposure.
- LC-MS/MS methodology for simultaneous determination of patulin and citrinin in urine and plasma applied to a pilot study in colorectal cancer patientsPublication . Ouhib, Salma; Vidal, Arnau; Martins, Carla; Gali, Ridha; Hedhili, Abderrazzeki; De Saeger, Sarah; De Boevre, MartheBiomarker-driven research has been proposed as a successful method to assess the exposure of individuals to xenobiotics, including mycotoxins, through estimation of their metabolites in biological fluids. A methodology to determine patulin (PAT) and citrinin (CIT) in human urine and plasma using liquid chromatography coupled to tandem mass spectrometry was developed and validated in the present study. Selectivity/specificity, linearity, limit of detection and quantification, apparent recovery, intraday- and interday-precision and measurement uncertainty were investigated for validation purposes. Finally, the method was used to analyze human urine (n = 100) and plasma (n = 100) case-control samples, where 50 samples originated from colorectal cancer patients and 50 from age/sex-matched controls. This case-control study revealed that PAT was not detected in urine samples, however occurred in 25% of the analysed plasma samples with an average concentration of 11.62 ± 6.67 ng/mL in the positive samples. CIT was found in urine samples (74%) and plasma samples (36%) with average concentrations in the positive samples of 0.45 ± 0.24 ng/mL and 0.49 ± 0.2 ng/mL respectively. No statistically significant difference of PAT and CIT concentration among colorectal cancer and control patients (p > 0.05) was observed.