Within this final report a detailed description of all tasks of the MYCOMIX project including a global evaluation is enclosed. The present project aims to explore the toxic effects of mixture of mycotoxins in infant food and potential health impact and includes a 1st task on multimycotoxin determination and legislation values, a 2nd on the evaluation of toxic effects of mycotoxin mixtures, a 3rd on bioaccessibility and absorption studies, a 4th on children exposure assessment and a final evaluation, the 5th task, on children´s health and mycotoxin mixtures. All tasks include an initial background and aims, materials and methods, results, deviations/comments, conclusions, references and project indicators. A final description of the total project output indicators is also included. ; FCT
Co-contamination of foodstuffs with multiple mycotoxins is being reported at an increasing high rate (Alvito et al, 2010; Stoev, 2015; Assunção et al, 2015) and this fact constitutes a rising concern due to the hazard of exposure of combined mycotoxins to humans, which could be expected to exert greater toxicity and carcinogenicity than exposure to single mycotoxins (Bouaziz et al., 2008; Grenier & Oswald, 2011). Most studies have focused on the risk assessment of single mycotoxins and there are scarce data concerning the risk associated with human exposure to multiple mycotoxins in foods, especially for those intended for children consumption (Assunção et al, 2016). Children are a vulnerable part of the population due to, in part, their physiology, a restricted diet and a higher consumption relative to their body thus particular attention must be given to the exposure of this population group to co-occurring food contaminants. Children in many parts of the world are routinely exposed to many mycotoxins in the food chain and the three most common are aflatoxins, fumonisins and deoxynivalenol (Etzel, 2006). For the main mycotoxin groups, maximum levels for regulatory purpose already exist for foodstuffs for adults and children consumption. European legislation (Commission Regulation 1881/2006), regulates processed cereal-based foods, infant formulae and baby foods for infants and young children with respect to mycotoxins contents. Children exposure to single mycotoxins with contents below legislated limits is considered safe to protect human health. Although, whether the children is also protected against a combined exposure to mycotoxins is unknown. MYCOMIX, a recent Portuguese project (https://www.youtube.com/watch?v=CsKaz3mt2J4), assessed for the first time, the risk associated with the simultaneous exposure to 13 mycotoxins in breakfast cereals, processed cereal-based foods and biscuits consumed by children until 3 years old from Lisbon region, Portugal (Assunção et al, 2015; Martins et al, in revision). Results on mycotoxins occurrence showed that 94% of the analysed samples were contaminated with at least one mycotoxin, although at levels below the legislated limits. Co-contamination was observed in 75% of the analysed samples. Estimated aflatoxins exposure suggested a potential adverse health effect for percentiles of intake above or equal to P50, determined through margin of exposure concept (Assunção et al, submitted). Studies on children exposure using mycotoxin biomarkers and attainment of detailed toxicological data, including health consequences associated to exposure to multiple mycotoxins, are needed in order to perform a more accurate risk assessment and to improve the protection of children´s health. ; N/A
Review article ; Most fungi are able to produce several mycotoxins simultaneously and, consequently, to contaminate a wide variety of foodstuffs. Therefore, the risk of human co-exposure to multiple mycotoxins is real, raising a growing concern about their potential impact on human health. Besides, government and industry regulations are usually based on individual toxicities, and do not take into account the complex dynamics associated with interactions between co-occurring groups of mycotoxins. The present work assembles, for the first time, the challenges posed by the likelihood of human co-exposure to these toxins and the possibility of interactive effects occurring after absorption, towards knowledge generation to support a more accurate human risk assessment. Regarding hazard assessment, a physiologically-based framework is proposed in order to infer the health effects from exposure to multiple mycotoxins in food, including knowledge on the bioaccessibility, toxicokinetics and toxicodynamics of single and combined toxins. The prioritisation of the most relevant mixtures to be tested under experimental conditions that attempt to mimic human exposure and the use of adequate mathematical approaches to evaluate interactions, particularly concerning the combined genotoxicity, were identified as the main challenges for hazard assessment. Regarding exposure assessment, the need of harmonised food consumption data, availability of multianalyte methods for mycotoxin quantification, management of left-censored data, use of probabilistic models and multibiomarker approaches are highlighted, in order to develop a more precise and realistic exposure assessment. To conclude, further studies on hazard and exposure assessment of multiple mycotoxins, using harmonised methodologies, are crucial towards an improvement of data quality and a more reliable and robust risk characterisation, which is central for risk management and, consequently, to prevent mycotoxins-associated adverse effects. A deep understanding of the nature of interactions between multiple mycotoxins will contribute to draw real conclusions on the health impact of human exposure to mycotoxin mixtures. ; This research was performed under the MycoMix project 'Exploring the toxic effects of mixtures of mycotoxins in infant food and potential health impact' (PTDC/DTP-FTO/0417/2012), through CESAM: UID/AMB/50017/2013 and ToxOmics: UID/BIM/00009/2013, all funded by the Fundação para a Ciência e Tecnologia (FCT), Portugal. ; info:eu-repo/semantics/publishedVersion
Historically, the health risk of mycotoxins had been evaluated on the basis of single-chemical and single-exposure pathway scenarios. However, the co-contamination of foodstuffs with these compounds is being reported at an increasing rate and a multiple-exposure scenario for humans and vulnerable population groups as children is urgently needed. Cereals are among the first solid foods eaten by child and thus constitute an important food group of their diet. Few data are available relatively to early stages child´s exposure to mycotoxins through consumption of cereal-based foods. The present study aims to perform the cumulative risk assessment of mycotoxins present in a set of cereal-based foods including breakfast cereals (BC), processed cereal-based foods (PCBF) and biscuits (BT), consumed by children (1 to 3 years old, n=75) from Lisbon region, Portugal. Children food consumption and occurrence of 12 mycotoxins (aflatoxins, ochratoxin A, fumonisins and trichothecenes) in cereal-based foods were combined to estimate the mycotoxin daily intake, using deterministic and probabilistic approaches. Different strategies were used to treat the left censored data. For aflatoxins, as carcinogenic compounds, the margin of exposure (MoE) was calculated as a ratio of BMDL (benchmark dose lower confidence limit) and aflatoxin daily exposure. For the remaining mycotoxins, the output of exposure was compared to the dose reference values (TDI) in order to calculate the hazard quotients (HQ, ratio between exposure and a reference dose). The concentration addition (CA) concept was used for the cumulative risk assessment of multiple mycotoxins. The combined margin of exposure (MoET) and the hazard index (HI) were calculated for aflatoxins and the remaining mycotoxins, respectively. Main results revealed a significant health concern related to aflatoxins and especially aflatoxin M1 exposure according to the MoET and MoE values (below 10000), respectively. HQ and HI values for the remaining mycotoxins were below 1, revealing a low concern from a public health point of view. These are the first results on cumulative risk assessment of multiple mycotoxins present in cereal-based foods consumed by children. Considering the present results, more research studies are needed to provide the governmental regulatory bodies with data to develop an approach that contemplate the human exposure and, particularly, children, to multiple mycotoxins in food. The last issue is particularly important considering the potential synergistic effects that could occur between mycotoxins and its potential impact on human and, mainly, children health. ; Study supported by Project Mycomix (PTDC/DTP-FTO/0417/2012, Foundation for Science and Technology), Portugal.
Mycotoxins are secondary metabolites of fungi that cause toxic and carcinogenic outcomes in humans exposed to them1. Mycotoxins affect several commodities including cereal grains and their finished products, infant formula and baby foods2. This study aimed to determine the incidence and levels of 20 mycotoxins and metabolites (AFB1, AFB2, AFG1, AFG2, AFM1, OTA, NIV, NEO, DAS, FUS-X, DON, 15-AC-DON, 3-AC-DON, HT-2, T-2, VER, T-2 TETROL, T-2 TRIOL), in breakfast cereals and cereal based baby foods available in the Portuguese market, and compare the results with the maximum limits established by the EU. Breakfast cereal samples (n=26), including corn, wheat, oat, rice and multigrain, and twenty cereal based baby foods (n=20) were collected from supermarkets in Lisbon region and analyzed by HPLC-FLD, LC-MS/MS and GC-MS. Results showed that 88 % breakfast cereals samples and 50 % of cereal based baby foods were contaminated with mycotoxins (with values above the detection limit), although all samples presented levels below the maximum limits established by the Commission Regulation 1881/20063. Regarding breakfast cereals samples, OTA and DON were the most commonly detected mycotoxins, with 88% and 73% of samples revealing values above the LOD, respectively. The co-occurrence of different mycotoxins in the same sample was observed in 92% of the analyzed samples. From these, 46% include mixtures of 3 or 4 mycotoxins. Regarding cereal based baby foods, OTA and AFM1 were the most commonly detected mycotoxins with 50% and 40% of samples revealing values above the LOD. The co-occurrence of mycotoxins was observed in 35% of the analyzed samples. These results are accordingly to those reported by Juan et al (2014)4 and Iqbal et al (2014)5. These results contribute to the increased knowledge on mycotoxin contents in cereal based foods marketed in Portugal, and they highlight the deep need of further studies to overcome the absence of legislated limits for mycotoxins in breakfast cereals other than DON and FB1 and the absence of legislated limits for mycotoxin mixtures in food. The last issue is particularly important considering the potential synergistic effects that could occur between mycotoxins and its potential impact on human and, mainly, children health. ; This research was performed under the MycoMix project (PTDC/DTP-FTO/0417/2012), funded by the Fundação para a Ciência e Tecnologia (FCT), Portugal
Climate change has been indicated as a driver for food safety issues worldwide, mainly due to the impact on the occurrence of food safety hazards at various stages of the food chain. Mycotoxins, natural contaminants produced by fungi, are among the most important of such hazards. Aflatoxins, which have the highest acute and chronic toxicity of all mycotoxins, assume particular importance. A recent study predicted aflatoxin contamination in maize and wheat crops in Europe within the next 100 years and aflatoxin B1 is predicted to become a food safety issue in Europe, especially in the most probable scenario of climate change (+2 °C). This review discusses the potential influence of climate change on the health risk associated with aflatoxins dietary exposure of Portuguese population. We estimated the burden of disease associated with the current aflatoxin exposure for Portuguese population in terms of Disability Adjusted Life Years (DALYs). It is expected that in the future the number of DALYs and the associated cases of hepatocellular carcinoma due to aflatoxins exposure will increase due to climate change. The topics highlighted through this review, including the potential impact on the health of the Portuguese population through the dietary exposure to aflatoxins, should represent an alert for the potential consequences of an incompletely explored perspective of climate change. Politics and decision-makers should be involved and committed to implementing effective measures to deal with climate change issues and to reduce its possible consequences. This review constitutes a contribution to the prioritization of strategies to face the unequal burden of effects of weather-related hazards in Portugal and across Europe. ; info:eu-repo/semantics/publishedVersion
In: Assunção , R , Martins , C , Viegas , S , Viegas , C , Jakobsen , L S , Pires , S M & Alvito , P 2018 , ' Climate change and the health impact of aflatoxins exposure in Portugal - an overview ' , Food Additives & Contaminants: Part A - Chemistry, Analysis, Control, Exposure & Risk Assessment , vol. 35 , no. 8 , pp. 1610-1621 . https://doi.org/10.1080/19440049.2018.1447691
Climate change has been indicated as a driver for food safety issues worldwide, mainly due to the impact on the occurrence of food safety hazards at various stages of food chain. Mycotoxins, natural contaminants produced by fungi, are among the most important of such hazards. Aflatoxins, which have the highest acute and chronic toxicity of all mycotoxins, assume particular importance. A recent study predicted aflatoxin contamination in maize and wheat crops in Europe within the next 100 years and aflatoxin B1 is predicted to become a food safety issue in Europe, especially in the most probable scenario of climate change (+2 °C). This review discusses the potential influence of climate change on the health risk associated to aflatoxins dietary exposure of Portuguese population. We estimated the burden of disease associated to the current aflatoxin exposure for Portuguese population in terms of Disability Adjusted Life Years (DALYs). It is expected that in the future the number of DALYs and the associated cases of hepatocellular carcinoma due to aflatoxins exposure will increase due to climate change. The topics highlighted through this review, including the potential impact on health of the Portuguese population through the dietary exposure to aflatoxins, should represent an alert for the potential consequences of an incompletely explored perspective of climate change. Politics and decision-makers should be involved and committed to implement effective measures to deal with climate change issues and to reduce its possible consequences. This review constitutes a contribution for the prioritisation of strategies to face the unequal burden of effects of weather-related hazards in Portugal and across Europe.
RiskBenefit4EU – Partnering to strengthen the risk–benefit assessment within EU using a holistic approach, is a recent European pilot project funded by EFSA and coordinated by Portugal (PT), integrating a multidisciplinary team from health and food institutes, national food safety authorities, R&D institutions and academia from PT, Denmark (DK) and France (FR). The main objectives of RiskBenefit4EU concerns the development of a set of Risk–Benefit Assessment (RBA) tools to assess and integrate food risks and benefits in the areas of microbiological, nutritional and chemical components through the development of a harmonised framework. This pilot project will validate the RBA framework created using a Portuguese case study on cereal-based foods. The research idea for food safety in risk assessment is to create an international network on RBA to promote and disseminate the outputs and knowledge acquired under RiskBenefir4EU, at European level. This network aims to promote knowledge and capacity building on RBA (acquired under RiskBenefit4EU) among European early stage researchers and to apply the harmonised framework on their countries. Health risks associated with consumption of cereal-based foods, an important source of nutrients with beneficial health effects, could increase soon due to climate changes in Europe (dry conditions and increased ambient temperatures could promote an increase in toxins production; occurrence of emergent compounds) so the dissemination and use of the RBA harmonized tools related with ingestion of cereal-based foods and derivatives could contribute to support future food and health policy in Europe. ; Projects GP/EFSA/AFSCO/2017/01-GA02 (EFSA), BioMAN/DAN/01 (INSA), UID/AMB/50017/2013 (CESAM) ; N/A
Human biomonitoring (HBM) is an important tool to survey the internal exposure of humans which represents the real life chemical body burden to chemicals and/or their metabolites. It results from total exposure to chemical substances from different sources and via different routes. These substances may be regulated under different legislative frameworks on chemicals (e.g., environmental, occupational, food safety etc). In occupational health, HBM has long traditions to control the exposures at workplaces. By providing accurate data on internal exposure, HBM data can improve human health risk assessment (RA) for both the general population and workers. Although the past few years have shown good examples on the use of HBM in the RA of chemicals, there is still quite some work to be done to improve its use in a regulatory RA. Under the scope of the European Human Biomonitoring Initiative (project HBM4EU, 2017-2021), the current study reviews the state-of-the-art of HBM use in chemicals RA with a special focus in Europe, and attempts to identify hurdles and challenges faced by regulators. To gather information on the use of HBM, including the availability of guidance on how to use it in RA, the RA schemes applied by different European or international organizations were analysed. Examples of such use were identified for a few selected groups of chemicals of concern for human health. In addition, we present the results of a survey, aimed at collecting information from national regulatory risk assessors on their day-to-day RA practices, the use of HBM data, and the obstacles and challenges related to their use. The results evidenced and explained some of the current obstacles of using HBM data in RA. These included the lack of HBM guidance values or biomonitoring equivalents (BEs), limited toxicokinetic information to support the interpretation of HBM data and, in the occupational health and safety (OSH) field, the lack of legal enforcement. Therefore, to support the integration of HBM in regulatory RA, we recommend, on one hand, the elaboration of a EU level guidance on the use of HBM in RA and, on the other hand, the continuation of research efforts to integrate HBM with new RA approaches using in vitro/in silico data and Adverse Outcome Pathways (AOPs). ; This project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 733032 HBM4EU, and received co-funding from the author's organizations. The authors thank to all other participants that contributed to this work. ; Sí
Human biomonitoring (HBM) is an important tool to survey the internal exposure of humans which represents the real life chemical body burden to chemicals and/or their metabolites. It results from total exposure to chemical substances from different sources and via different routes. These substances may be regulated under different legislative frameworks on chemicals (e.g., environmental, occupational, food safety etc). In occupational health, HBM has long traditions to control the exposures at workplaces. By providing accurate data on internal exposure, HBM data can improve human health risk assessment (RA) for both the general population and workers. Although the past few years have shown good examples on the use of HBM in the RA of chemicals, there is still quite some work to be done to improve its use in a regulatory RA. Under the scope of the European Human Biomonitoring Initiative (project HBM4EU, 2017–2021), the current study reviews the state-of-the-art of HBM use in chemicals RA with a special focus in Europe, and attempts to identify hurdles and challenges faced by regulators. To gather information on the use of HBM, including the availability of guidance on how to use it in RA, the RA schemes applied by different European or international organizations were analysed. Examples of such use were identified for a few selected groups of chemicals of concern for human health. In addition, we present the results of a survey, aimed at collecting information from national regulatory risk assessors on their day-to-day RA practices, the use of HBM data, and the obstacles and challenges related to their use. The results evidenced and explained some of the current obstacles of using HBM data in RA. These included the lack of HBM guidance values or biomonitoring equivalents (BEs), limited toxicokinetic information to support the interpretation of HBM data and, in the occupational health and safety (OSH) field, the lack of legal enforcement. Therefore, to support the integration of HBM in regulatory RA, we recommend, on one hand, the elaboration of a EU level guidance on the use of HBM in RA and, on the other hand, the continuation of research efforts to integrate HBM with new RA approaches using in vitro/in silico data and Adverse Outcome Pathways (AOPs).
In: Louro , H , Heinälä , M , Bessems , J , Buekers , J , Vermeire , T , Woutersen , M , van Engelen , J , Borges , T , Rousselle , C , Ougier , E , Alvito , P , Martins , C , Assunção , R , Silva , M J , Pronk , A , Schaddelee-Scholten , B , Del Carmen Gonzalez , M , de Alba , M , Castaño , A , Viegas , S , Humar-Juric , T , Kononenko , L , Lampen , A , Vinggaard , A M , Schoeters , G , Kolossa-Gehring , M & Santonen , T 2019 , ' Human biomonitoring in health risk assessment in Europe : Current practices and recommendations for the future ' , International Journal of Hygiene and Environmental Health , vol. 222 , no. 5 , pp. 727-737 . https://doi.org/10.1016/j.ijheh.2019.05.009
Human biomonitoring (HBM) is an important tool to survey the internal exposure of humans which represents the real life chemical body burden to chemicals and/or their metabolites. It results from total exposure to chemical substances from different sources and via different routes. These substances may be regulated under different legislative frameworks on chemicals (e.g., environmental, occupational, food safety etc). In occupational health, HBM has long traditions to control the exposures at workplaces. By providing accurate data on internal exposure, HBM data can improve human health risk assessment (RA) for both the general population and workers. Although the past few years have shown good examples on the use of HBM in the RA of chemicals, there is still quite some work to be done to improve its use in a regulatory RA. Under the scope of the European Human Biomonitoring Initiative (project HBM4EU, 2017–2021), the current study reviews the state-of-the-art of HBM use in chemicals RA with a special focus in Europe, and attempts to identify hurdles and challenges faced by regulators. To gather information on the use of HBM, including the availability of guidance on how to use it in RA, the RA schemes applied by different European or international organizations were analysed. Examples of such use were identified for a few selected groups of chemicals of concern for human health. In addition, we present the results of a survey, aimed at collecting information from national regulatory risk assessors on their day-to-day RA practices, the use of HBM data, and the obstacles and challenges related to their use. The results evidenced and explained some of the current obstacles of using HBM data in RA. These included the lack of HBM guidance values or biomonitoring equivalents (BEs), limited toxicokinetic information to support the interpretation of HBM data and, in the occupational health and safety (OSH) field, the lack of legal enforcement. Therefore, to support the integration of HBM in regulatory RA, we recommend, ...
International audience ; Human biomonitoring (HBM) is an important tool to survey the internal exposure of humans which represents the real life chemical body burden to chemicals and/or their metabolites. It results from total exposure to chemical substances from different sources and via different routes. These substances may be regulated under different legislative frameworks on chemicals (e.g., environmental, occupational, food safety etc). In occupational health, HBM has long traditions to control the exposures at workplaces. By providing accurate data on internal exposure, HBM data can improve human health risk assessment (RA) for both the general population and workers. Although the past few years have shown good examples on the use of HBM in the RA of chemicals, there is still quite some work to be done to improve its use in a regulatory RA. Under the scope of the European Human Biomonitoring Initiative (project HBM4EU, 2017-2021), the current study reviews the state-of-the-art of HBM use in chemicals RA with a special focus in Europe, and attempts to identify hurdles and challenges faced by regulators. To gather information on the use of HBM, including the availability of guidance on how to use it in RA, the RA schemes applied by different European or international organizations were analysed. Examples of such use were identified for a few selected groups of chemicals of concern for human health. In addition, we present the results of a survey, aimed at collecting information from national regulatory risk assessors on their day-to-day RA practices, the use of HBM data, and the obstacles and challenges related to their use. The results evidenced and explained some of the current obstacles of using HBM data in RA. These included the lack of HBM guidance values or biomonitoring equivalents (BEs), limited toxicokinetic information to support the interpretation of HBM data and, in the occupational health and safety (OSH) field, the lack of legal enforcement. Therefore, to support the integration of HBM in ...
International audience ; Human biomonitoring (HBM) is an important tool to survey the internal exposure of humans which represents the real life chemical body burden to chemicals and/or their metabolites. It results from total exposure to chemical substances from different sources and via different routes. These substances may be regulated under different legislative frameworks on chemicals (e.g., environmental, occupational, food safety etc). In occupational health, HBM has long traditions to control the exposures at workplaces. By providing accurate data on internal exposure, HBM data can improve human health risk assessment (RA) for both the general population and workers. Although the past few years have shown good examples on the use of HBM in the RA of chemicals, there is still quite some work to be done to improve its use in a regulatory RA. Under the scope of the European Human Biomonitoring Initiative (project HBM4EU, 2017-2021), the current study reviews the state-of-the-art of HBM use in chemicals RA with a special focus in Europe, and attempts to identify hurdles and challenges faced by regulators. To gather information on the use of HBM, including the availability of guidance on how to use it in RA, the RA schemes applied by different European or international organizations were analysed. Examples of such use were identified for a few selected groups of chemicals of concern for human health. In addition, we present the results of a survey, aimed at collecting information from national regulatory risk assessors on their day-to-day RA practices, the use of HBM data, and the obstacles and challenges related to their use. The results evidenced and explained some of the current obstacles of using HBM data in RA. These included the lack of HBM guidance values or biomonitoring equivalents (BEs), limited toxicokinetic information to support the interpretation of HBM data and, in the occupational health and safety (OSH) field, the lack of legal enforcement. Therefore, to support the integration of HBM in regulatory RA, we recommend, on one hand, the elaboration of a EU level guidance on the use of HBM in RA and, on the other hand, the continuation of research efforts to integrate HBM with new RA approaches using in vitro/in silico data and Adverse Outcome Pathways (AOPs).