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Alvito, P.;  Assunção, R.M.;  Bajard, L.;  Martins, C.;  Mengelers, M.J.B.;  Mol, H.;  Namorado, S.;  Brand, A.D.V.D.;  Vasco, E.;  Viegas, S.; et al. Mycotoxins in the Context of HBM4EU Initiative. Encyclopedia. Available online: https://encyclopedia.pub/entry/38210 (accessed on 18 April 2024).
Alvito P,  Assunção RM,  Bajard L,  Martins C,  Mengelers MJB,  Mol H, et al. Mycotoxins in the Context of HBM4EU Initiative. Encyclopedia. Available at: https://encyclopedia.pub/entry/38210. Accessed April 18, 2024.
Alvito, Paula, Ricardo Manuel Assunção, Lola Bajard, Carla Martins, Marcel J. B. Mengelers, Hans Mol, Sónia Namorado, Annick D. Van Den Brand, Elsa Vasco, Susana Viegas, et al. "Mycotoxins in the Context of HBM4EU Initiative" Encyclopedia, https://encyclopedia.pub/entry/38210 (accessed April 18, 2024).
Alvito, P.,  Assunção, R.M.,  Bajard, L.,  Martins, C.,  Mengelers, M.J.B.,  Mol, H.,  Namorado, S.,  Brand, A.D.V.D.,  Vasco, E.,  Viegas, S., & Silva, M.J. (2022, December 07). Mycotoxins in the Context of HBM4EU Initiative. In Encyclopedia. https://encyclopedia.pub/entry/38210
Alvito, Paula, et al. "Mycotoxins in the Context of HBM4EU Initiative." Encyclopedia. Web. 07 December, 2022.
Mycotoxins in the Context of HBM4EU Initiative
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Mycotoxins are natural metabolites produced by fungi that contaminate food and feed worldwide. They can pose a threat to human and animal health, mainly causing chronic effects, e.g., immunotoxic and carcinogenic. Due to climate change, an increase in European population exposure to mycotoxins is expected to occur, raising public health concerns. This urges researchers to assess the current human exposure to mycotoxins in Europe to allow monitoring exposure and prevent future health impacts. The mycotoxins deoxynivalenol (DON) and fumonisin B1 (FB1) were considered as priority substances to be studied within the European Human Biomonitoring Initiative (HBM4EU) to generate knowledge on internal exposure and their potential health impacts.

human biomonitoring risk assessment HBM4EU human health mycotoxins exposure

1. Human Exposure to Mycotoxins

Mycotoxins are secondary fungal metabolites often found as natural contaminants in agricultural commodities all over the world. They are closely associated with the consumption of crops previously contaminated with mycotoxigenic fungi, particularly cereals, although they also appear in fruits, vegetables, and animal products, including meat, dairy, and eggs [1][2]. Generally, mycotoxins are chemically and thermally stable compounds, surviving storage and most production process [3]. Their occurrence in such a variety of food and derived products is associated with human (and animal) exposure to mycotoxins on a daily basis, posing a risk to human and animal health. Food is the main source of exposure, and ingestion is the main route of exposure, to mycotoxins. In addition, inhalation and dermal routes can also contribute to exposure in certain occupational settings, mainly during tasks involving high exposure to organic dust (e.g., storage work, loading, handling, or milling contaminated grains, waste and feed) because airborne dust, spores, and hyphae fragments can act as carriers of mycotoxins to the lungs [4][5]. Currently, the main human and animal health burdens of mycotoxin exposure are related to chronic toxicity, such as carcinogenic, teratogenic, immunotoxic, nephrotoxic, and endocrine-disrupting effects. As such, it is crucial that the human exposure to mycotoxins is unraveled, which can be achieved either by determining mycotoxin occurrence in food products or by performing epidemiological and human biomonitoring studies, including the measurement of mycotoxins or their metabolites in human biological specimens. The latter, known as the direct approach, gives reliable insights into the internal dose achieved in the organism upon mycotoxin exposure.
The European Union has set maximum concentrations for mycotoxins in a range of foodstuffs to protect human health [6]. Besides these regulated mycotoxins, several other non-regulated toxins, such as modified and emerging mycotoxins, have been also reported in various foodstuffs [7][8][9]. Furthermore, co-exposure to several mycotoxins has been commonly found. However, their combined effect on human health needs to be considered and taken on board at a regulatory level when defining maximum concentrations [10]. In addition, mycotoxins are still not recognized as a risk factor present in the workplace, probably due to the lack of information and knowledge concerning changes on mycotoxin toxicokinetics when exposure occurs by inhalation and/or dermal absorption. These limitations might explain why there is no occupational exposure limit set for any mycotoxin [5]. Due to climate change, an increased magnitude and/or frequency of human exposure to mycotoxins is expected to occur, particularly in the current temperate regions of Europe. Additionally, mycotoxins that have not been commonly reported in food commodities from European Union (EU) countries might begin to occur as a result of changes in fungi species distribution associated with climate change [11][12][13][14]. For example, a wider dissemination of Fusarium fungi and its respective toxins is expected and will increase human (and animal) exposure and the prevalence of related health outcomes [15].
In summary, a different exposure pattern to mycotoxins might occur in the near future, or has already started to occur in the EU population, due to the ongoing climate change scenario observed in Europe. Therefore, there is a need to assess the current EU population’s exposure to mycotoxins that will serve as a baseline to monitor and compare future exposure, especially of vulnerable population groups, such as children and pregnant women, to assess the associated risk of developing health outcomes.

2. Mycotoxins in the Context of the HBM4EU Initiative

Human biomonitoring (HBM) consists of the measurement of a chemical or its metabolites (corresponding to the biomarkers of exposure) in body fluids or tissues, such as blood, urine, milk and hair [16][17]. HBM allows the determination of the internal exposure of individuals to chemicals, integrating all the exposure sources (e.g., food and air) and routes simultaneously [17]. Several HBM initiatives, from local to international, have been developed during the last few years in order to support the assessment of risk resulting from the human exposure to chemicals with proper exposure data. In addition to exposure biomarkers, the use of effect biomarkers in HBM studies contributes to establishing a link between internal exposure and early subclinical alterations that are suggestive of long-term health effects. Effect biomarkers consist of measurable biochemical, physiological, and behavioral effects within an organism that can be recognized as associated with an established or possible health impairment or disease [18].
The EU’s Environment and Health Action Plan 2004–2010 recognized the value of HBM and called for a coherent approach to biomonitoring in Europe [19]. Following two previous projects on HBM (COPHES and DEMOCOPHES), the European HBM Initiative (HBM4EU, 2017–2022) was set up with the main goal of coordinating and advancing HBM in Europe to provide science-based evidence for chemical policy development and improve chemical management [20].
A prioritization strategy to identify the chemicals or groups of chemicals to be studied under the HBM4EU [21] was implemented to determine and meet the most important needs of both policy makers and risk assessors, as well as the common national needs of participating countries and a broad range of stakeholders [22]. Following this strategy, mycotoxins were considered a priority substance group. Given the wide variety of compounds comprising mycotoxins, the EU Policy Board, the European Food Safety Authority (EFSA) and the Directorate-General for Health and Food Safety (DG SANTE) were consulted to allow the selection of the priority mycotoxins to be studied under the Project. The focus was set on deoxynivalenol (DON) and fumonisin B1 (FB1), for which data gaps regarding exposure and/or hazard are urged to be filled [23]. Although it has been recognized that exposure to mycotoxin mixtures is common and may lead to adverse health effects difficult to predict from the effects of single toxins, this topic was not addressed here. A scoping document containing a review of hazardous properties, exposure characteristics, policy relevance, technical aspects and the societal concern of mycotoxins, as well as a list of detailed policy-related questions, summarised in Table 1, identifying knowledge gaps and proposing research activities to close those gaps, was elaborated [24].
Table 1. Policy questions on mycotoxin human biomonitoring under the HBM4EU according to risk assessment steps.
The policy questions addressed for these mycotoxins under the HBM4EU Initiative were driven by three main areas that constitute the steps of the chemicals risk assessment (RA), as illustrated at Figure 1: hazard assessment (including hazard identification and characterization), exposure assessment and risk characterization.
Figure 1. Human Biomonitoring and Risk Assessment of mycotoxins (compliance with RA components). AOP—adverse outcome pathway, HBM-GV—Human Biomonitoring Guidance Value.
The exposure assessment step considers the choice of exposure biomarkers, respective specimens and the analytical methods for the evaluation of the magnitude and frequency of exposure, as well as the identification of the population groups that might be potentially highly exposed. The hazard assessment aimed at estimating internal exposures, identifying the main health effects reported in human and animal studies and contributing to elucidate the metabolic pathways and obtained toxicokinetics data that will support the choice of the most adequate exposure biomarkers. Finally, the adverse outcome pathway (AOP) framework [25] was used to organize the available knowledge from in vivo and in vitro studies to understand the biological mechanisms leading from the molecular or cellular perturbations to the health endpoints that are of regulatory relevance. A Human Biomonitoring Guidance Value (HBM-GV) was further developed, allowing the risk characterization of the target mycotoxins from the HBM data obtained for the European adult population.

3. Prioritized Mycotoxins: Occurrence, Toxicological Properties and Exposure Thresholds

Both DON and FB1 are produced by Fusarium species and occur predominantly in cereal grains. They are regulated in various cereal and derived products, being extensively measured in food in the EU through the monitoring programs in place [6].
DON is mainly found in wheat, oats, barley, maize and consequently also in cereal products such as breakfast cereals, bread, pasta and beer. It has been considered as immunotoxic, reprotoxic and a potential endocrine disruptor, and also induces intestinal disorders [26][27]. There is no evidence that DON could be carcinogenic to humans and, therefore, it is classified into Group 3 by the International Agency for Research on Cancer (IARC) [28]. A group tolerable daily intake (TDI) of 1 µg/kg bw/day was set for this mycotoxin and its derivatives, including 3-acetyl-deoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), and deoxynivalenol-3-glucoside (DON-3G), based on reduced body weight gain in mice and assuming a chronic exposure to DON. However, an acute reference dose was also derived of 8 µg/kg bw per eating occasion, related to gastrointestinal effects that were reported in humans following exposure to high levels of DON in China [26]. The estimated mean chronic dietary exposure has been found to lie above the group-TDI in infants, toddlers and other children, and in highly exposed adolescents and adults, indicating a potential health concern [26].
Fumonisins (FB1, FB2, FB3 and FB4) are present mostly in maize and sorghum, with FB1 typically being the dominant one [29]. It is a suspected mutagen and a possible carcinogen, and thus classified by IARC in Group 2B [30]. It is teratogenic and associated with neural tube defects in the embryo. A group TDI value of 1 µg/kg bw/day was set for FB1, FB2, FB3 and FB4 considering a BMDL10 of 0.1 mg/kg bw/day for megalocytic hepatocytes in mice [29]. There are no indications of acute adverse effects upon exposure to FB1.

References

  1. Bennett, J.W.; Klich, M. Mycotoxins. Clin. Microbiol. Rev. 2003, 16, 497–516.
  2. Wu, F.; Groopman, J.D.; Pestka, J.J. Public Health Impacts of Foodborne Mycotoxins. Annu. Rev. Food Sci. Technol. 2014, 5, 351–372.
  3. Köppen, R.; Koch, M.; Siegel, D.; Merkel, S.; Maul, R.; Nehls, I. Determination of Mycotoxins in Foods: Current State of Analytical Methods and Limitations. Appl. Microbiol. Biotechnol. 2010, 86, 1595–1612.
  4. Louro, H.; Heinälä, M.; Bessems, J.; Buekers, J.; Vermeire, T.; Woutersen, M.; Van Engelen, J.; Borges, T.; Rousselle, C.; Ougier, E.; et al. International Journal of Hygiene and Human Biomonitoring in Health Risk Assessment in Europe: Current Practices and Recommendations for the Future. Int. J. Hyg. Environ. Health 2019, 222, 727–737.
  5. Viegas, S.; Viegas, C.; Oppliger, A. Occupational Exposure to Mycotoxins: Current Knowledge and Prospects. Ann. Work Expo. Health 2018, 62, 923–941.
  6. European Commission (EU). Commission Regulation (EC) No 1881/2006 of 19 December 2006 Setting Maximum Levels for Certain Contaminants in Foodstuffs. EFSA J. 2006, 364, 5–24.
  7. EFSA CONTAM Panel (EFSA Panel on Contaminants in the Food Chain). Scientific Opinion on the Risks for Human and Animal Health Related to the Presence of Modified Forms of Certain Mycotoxins in Food and Feed. EFSA J. 2014, 12, 3916.
  8. Gruber-Dorninger, C.; Novak, B.; Nagl, V.; Berthiller, F. Emerging Mycotoxins: Beyond Traditionally Determined Food Contaminants. J. Agric. Food Chem. 2017, 65, 7052–7070.
  9. Ekwomadu, T.I.; Akinola, S.A.; Mwanza, M. Fusarium Mycotoxins, Their Metabolites (Free, Emerging, and Masked), Food Safety Concerns, and Health Impacts. Int. J. Environ. Res. Public Health 2021, 18, 11741.
  10. Alvito, P.; Barcelo, J.; De Meester, J.; Rito, E.; Suman, M. Mitigation of Mycotoxins during Food Processing: Sharing Experience among Europe and South East Asia. Sci. Technol. Cereal. Oils Foods 2021, 29, 59–70.
  11. Miraglia, M.; Marvin, H.J.P.; Kleter, G.A.; Battilani, P.; Brera, C.; Coni, E.; Cubadda, F.; Croci, L.; De Santis, B.; Dekkers, S.; et al. Climate Change and Food Safety: An Emerging Issue with Special Focus on Europe. Food Chem. Toxicol. 2009, 47, 1009–1021.
  12. Battilani, P.; Toscano, P.; Van Der Fels-Klerx, H.J.; Moretti, A.; Camardo Leggieri, M.; Brera, C.; Rortais, A.; Goumperis, T.; Robinson, T. Aflatoxin B 1 Contamination in Maize in Europe Increases Due to Climate Change. Sci. Rep. 2016, 6, 1–7.
  13. Assunção, R.; Martins, C.; Viegas, S.; Viegas, C.; Jakobsen, L.S.; Pires, S.; Alvito, P. Climate Change and the Health Impact of Aflatoxins Exposure in Portugal–an Overview. Food Addit. Contam. Part A Chem. Anal. Control. Expo. Risk Assess. 2018, 35, 1610–1621.
  14. Alvito, P.; Assunção, R. Climate Change and the Impact on Aflatoxin Contamination in Foods: Where Are We and What Should Be Expected? In Aflatoxins in Food; Springer: Cham, Switzerland, 2021; ISBN 9783030857615.
  15. Zingales, V.; Taroncher, M.; Martino, P.A.; Caloni, F. Climate Change and Effects on Molds and Mycotoxins. Toxins 2022, 14, 445.
  16. Bizjak, T.; Capodiferro, M.; Deepika, D.; Dinçkol, Ö.; Dzhedzheia, V.; Lopez-Suarez, L.; Petridis, I.; Runkel, A.A.; Schultz, D.R.; Kontić, B. Human Biomonitoring Data in Health Risk Assessments Published in Peer-Reviewed Journals between 2016 and 2021: Confronting Reality after a Preliminary Review. Int. J. Environ. Res. Public Health 2022, 19, 3362.
  17. Choi, J.; Aarøe Mørck, T.; Polcher, A.; Knudsen, L.E.; Joas, A. Review of the State of the Art of Human Biomonitoring for Chemical Substances and Its Application to Human Exposure Assessment for Food Safety. EFSA Support. Publ. 2015, 12, 724.
  18. World Health Organisation (WHO). Biomarkers and Risk Assessment: Concepts and Principles. Environmental Health Criteria 155; WHO Library Cataloguing in Publication Data: Vammala, Finland, 1993; ISBN 9241571551.
  19. European Commission. EUR-Lex–52004DC0416–EN 2004. Available online: https://eur-lex.europa.eu/legal-content/EN/TXT/HTML/?uri=CELEX:52004DC0416&from=EN (accessed on 4 July 2022).
  20. Ganzleben, C.; Antignac, J.P.; Barouki, R.; Castaño, A.; Fiddicke, U.; Klánová, J.; Lebret, E.; Olea, N.; Sarigiannis, D.; Schoeters, G.R.; et al. Human Biomonitoring as a Tool to Support Chemicals Regulation in the European Union. Int. J. Hyg. Environ. Health 2017, 220, 94–97.
  21. Ormsby, J.-N.; Lecoq, P.; Ougier, E.; Rousselle, C.; Ganzleben, C. HBM4EU—Prioritisation, Strategy and Criteria, Deliverable Report D4.3; 2017. Available online: https://www.hbm4eu.eu/work-packages/deliverable-4-3-prioritisation-strategy-and-criteria/ (accessed on 12 July 2022).
  22. Ougier, E.; Ganzleben, C.; Lecoq, P.; Bessems, J.; David, M.; Schoeters, G.; Lange, R.; Meslin, M.; Uhl, M.; Kolossa-gehring, M.; et al. Chemical Prioritisation Strategy in the European Human Biomonitoring Initiative (HBM4EU)—Development and Results. Int. J. Hyg. Environ. Health 2021, 236, 113778.
  23. Schoeters, G.; Rosa, L.; Kolossa, M.; Barouki, R.; Tarroja, E.; Uhl, M.; Klanova, J.; Melymuk, L.; Horvat, M.; Bocca, B.; et al. HBM4EU—Scoping Documents for 2021 for the First and Second Second Round HBM4EU Priority Substances Deliverable Report D4.9. 2021. Available online: https://www.hbm4eu.eu/work-packages/deliverable-4-9-scoping-documents-for-2021-for-the-first-and-second-second-round-hbm4eu-priority-substances/ (accessed on 12 July 2022).
  24. Schoeters, G.; Lange, R.; Laguzzi, F.; Kadikis, N.; Wasowicz, W.; Santonen, T.; Mahiout, S.; Rudnai, P.; Katsonouri-Sazeides, A.; Alvito, P.; et al. HBM4EU—Scoping Documents for the Second Round Priority Substances Deliverable Report D4.6; 2019. Available online: https://www.hbm4eu.eu/work-packages/deliverable-4-6-scoping-documents-for-the-second-round-priority-substances/ (accessed on 12 July 2022).
  25. Ankley, G.T.; Bennett, R.S.; Erickson, R.J.; Hoff, D.J.; Hornung, M.W.; Johnson, R.D.; Mount, D.R.; Nichols, J.W.; Russom, C.L.; Schmieder, P.K.; et al. Adverse Outcome Pathways: A Conceptual Framework to Support Ecotoxicology Research and Risk Assessment. Environ. Toxicol. Chem. 2010, 29, 730–741.
  26. EFSA CONTAM Panel (EFSA Panel on Contaminants in the Food Chain); Knutsen, H.K.; Alexander, J.; Barregård, L.; Bignami, M.; Brüschweiler, B.; Ceccatelli, S.; Cottrill, B.; Dinovi, M.; Grasl-Kraupp, B.; et al. Risks to Human and Animal Health Related to the Presence of Deoxynivalenol and Its Acetylated and Modified Forms in Food and Feed. EFSA J. 2017, 15, 4718.
  27. Ndossi, D.G.; Frizzell, C.; Tremoen, N.H.; Fæste, C.K.; Verhaegen, S.; Dahl, E.; Eriksen, G.S.; Sørlie, M.; Connolly, L.; Ropstad, E. An in Vitro Investigation of Endocrine Disrupting Effects of Trichothecenes Deoxynivalenol (DON), T-2 and HT-2 Toxins. Toxicol. Lett. 2012, 214, 268–278.
  28. IARC. Some Naturally Occurring Susbtances: Food Items and Constituents, Heterocyclic Aromatic Amines and Mycotoxins; IARC: Lyon, France, 1993; ISBN 9283212568.
  29. EFSA CONTAM Panel (EFSA Panel on Contaminants in the Food Chain); Knutsen, H.K.; Barregård, L.; Bignami, M.; Brüschweiler, B.; Ceccatelli, S.; Cottrill, B.; Dinovi, M.; Edler, L.; Grasl-Kraupp, B.; et al. Appropriateness to Set a Group Health-Based Guidance Value for Fumonisins and Their Modified Forms. EFSA J. 2018, 16, 5172.
  30. IARC. Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and Styrene; IARC: Lyon, France, 2002; Volume 82, ISBN 9789283215875.
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