Challenges in risk assessment of multiple mycotoxins in food

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 t...

[1]  S. Tittlemier,et al.  Developments in mycotoxin analysis: an update for 2016-2017 , 2018 .

[2]  I. Oswald,et al.  Mycotoxins co-contamination: Methodological aspects and biological relevance of combined toxicity studies , 2017, Critical reviews in food science and nutrition.

[3]  H. Mol,et al.  Strategies for estimating human exposure to mycotoxins via food , 2016 .

[4]  S. Turgeon,et al.  The harmonized INFOGEST in vitro digestion method: From knowledge to action , 2016 .

[5]  D. Dupont,et al.  Patulin and ochratoxin A co-occurrence and their bioaccessibility in processed cereal-based foods: A contribution for Portuguese children risk assessment. , 2016, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[6]  M. Zeilmaker,et al.  A mycotoxin-dedicated total diet study in the Netherlands in 2013: Part I – Design , 2016 .

[7]  J. D. Biesebeek,et al.  A mycotoxin-dedicated total diet study in the Netherlands in 2013: Part III – exposure and risk assessment , 2016 .

[8]  R. Krska,et al.  Developments in mycotoxin analysis: an update for 2014-2015 , 2016 .

[9]  B. Warth,et al.  Non-synergistic cytotoxic effects of Fusarium and Alternaria toxin combinations in Caco-2 cells. , 2016, Toxicology letters.

[10]  S. Piletsky,et al.  Analytical methods for determination of mycotoxins: An update (2009-2014). , 2015, Analytica chimica acta.

[11]  E. Ferrer,et al.  Analysis of mycotoxins in coffee and risk assessment in Spanish adolescents and adults. , 2015, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[12]  P. Alvito,et al.  Single-compound and cumulative risk assessment of mycotoxins present in breakfast cereals consumed by children from Lisbon region, Portugal. , 2015, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[13]  S. De Henauw,et al.  Human biomonitoring of multiple mycotoxins in the Belgian population: Results of the BIOMYCO study. , 2015, Environment international.

[14]  I. Huybrechts,et al.  Dietary mycotoxins, co-exposure, and carcinogenesis in humans: Short review. , 2015, Mutation research. Reviews in mutation research.

[15]  C. Frizzell,et al.  Challenging conventional risk assessment with respect to human exposure to multiple food contaminants in food: A case study using maize. , 2015, Toxicology letters.

[16]  H. Louro,et al.  Risk assessment of multiple mycotoxins in infant food consumed by Portuguese children – the contribute of the MYCOMIX project , 2015 .

[17]  H. Louro,et al.  A contribution to hazard assessment of combined exposure to mycotoxins using in vitro toxicity testing , 2015 .

[18]  M. Solfrizzo,et al.  Biomonitoring of concurrent mycotoxin exposure among adults in Sweden through urinary multi-biomarker analysis. , 2015, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[19]  H. Yoon,et al.  Total Diet Studies as a Tool for Ensuring Food Safety , 2015, Toxicological research.

[20]  Jian Ji,et al.  A novel and simple cell-based electrochemical impedance biosensor for evaluating the combined toxicity of DON and ZEN. , 2015, Biosensors & bioelectronics.

[21]  I. Oswald,et al.  Toxicological interactions between the mycotoxins deoxynivalenol, nivalenol and their acetylated derivatives in intestinal epithelial cells , 2015, Archives of Toxicology.

[22]  B. Shao,et al.  Natural Occurrence of Alternaria Toxins in Wheat-Based Products and Their Dietary Exposure in China , 2015, PloS one.

[23]  H. Humpf,et al.  A comparative study of the human urinary mycotoxin excretion patterns in Bangladesh, Germany, and Haiti using a rapid and sensitive LC-MS/MS approach , 2015, Mycotoxin Research.

[24]  S. Stoev Foodborne mycotoxicoses, risk assessment and underestimated hazard of masked mycotoxins and joint mycotoxin effects or interaction. , 2015, Environmental toxicology and pharmacology.

[25]  I. Sioen,et al.  TDS exposure project: application of the analytic hierarchy process for the prioritization of substances to be analyzed in a total diet study. , 2015, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[26]  A. Azqueta,et al.  Genotoxicity of Aflatoxin B1 and Ochratoxin A after simultaneous application of the in vivo micronucleus and comet assay. , 2015, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[27]  A. Visconti,et al.  Assessment of toxic potential of mycotoxin contaminated bread during in vitro human digestion on human B lymphoid cell line. , 2015, Toxicology letters.

[28]  Bo Chen,et al.  Cumulative health risk assessment of co-occurring mycotoxins of deoxynivalenol and its acetyl derivatives in wheat and maize: case study, Shanghai, China. , 2014, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[29]  H. Humpf,et al.  Determination of mycotoxin exposure in Germany using an LC-MS/MS multibiomarker approach. , 2014, Molecular nutrition & food research.

[30]  C. Frizzell,et al.  Cytotoxic assessment of the regulated, co-existing mycotoxins aflatoxin B1, fumonisin B1 and ochratoxin, in single, binary and tertiary mixtures. , 2014, Toxicon : official journal of the International Society on Toxinology.

[31]  Rudolf Krska,et al.  Optimization and validation of a quantitative liquid chromatography-tandem mass spectrometric method covering 295 bacterial and fungal metabolites including all regulated mycotoxins in four model food matrices. , 2014, Journal of chromatography. A.

[32]  Cian O'Mahony,et al.  Statistical method to assess usual dietary intakes in the European population , 2014, Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment.

[33]  J. Mañes,et al.  Development of a GC-MS/MS strategy to determine 15 mycotoxins and metabolites in human urine. , 2014, Talanta.

[34]  J. Mañes,et al.  Exposure assessment approach through mycotoxin/creatinine ratio evaluation in urine by GC-MS/MS. , 2014, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[35]  V. Dohnal,et al.  Metabolism of aflatoxins: key enzymes and interindividual as well as interspecies differences , 2014, Archives of Toxicology.

[36]  M. Corredig,et al.  A standardised static in vitro digestion method suitable for food - an international consensus. , 2014, Food & function.

[37]  R. Krska,et al.  Mycotoxin exposure in rural residents in northern Nigeria: a pilot study using multi-urinary biomarkers. , 2014, Environment international.

[38]  S. De Henauw,et al.  Assessment of mycotoxin exposure in the Belgian population using biomarkers: aim, design and methods of the BIOMYCO study , 2014, Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment.

[39]  W. Föllmann,et al.  Toxicity of the mycotoxin citrinin and its metabolite dihydrocitrinone and of mixtures of citrinin and ochratoxin A in vitro , 2014, Archives of Toxicology.

[40]  J. Groopman,et al.  Public health impacts of foodborne mycotoxins. , 2014, Annual review of food science and technology.

[41]  F. Papachristou,et al.  Mycotoxins’ Activity at Toxic and Sub-Toxic Concentrations: Differential Cytotoxic and Genotoxic Effects of Single and Combined Administration of Sterigmatocystin, Ochratoxin A and Citrinin on the Hepatocellular Cancer Cell Line Hep3B , 2014, International journal of environmental research and public health.

[42]  A. Visconti,et al.  Assessment of Multi-Mycotoxin Exposure in Southern Italy by Urinary Multi-Biomarker Determination , 2014, Toxins.

[43]  A. Kortenkamp,et al.  Genotoxic mixtures and dissimilar action: concepts for prediction and assessment , 2013, Archives of Toxicology.

[44]  R. Krska,et al.  Multiple mycotoxin exposure determined by urinary biomarkers in rural subsistence farmers in the former Transkei, South Africa. , 2013, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[45]  R. Krska,et al.  Bio-monitoring of mycotoxin exposure in Cameroon using a urinary multi-biomarker approach. , 2013, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[46]  M. Klarić,et al.  Deleterious Effects of Mycotoxin Combinations Involving Ochratoxin A , 2013, Toxins.

[47]  P. Cressey,et al.  Dietary exposure and risk assessment for aflatoxins in New Zealand , 2013 .

[48]  G. Cano-Sancho,et al.  Mycotoxins: occurrence, toxicology, and exposure assessment. , 2013, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[49]  I. Oswald,et al.  New insights into mycotoxin mixtures: the toxicity of low doses of Type B trichothecenes on intestinal epithelial cells is synergistic. , 2013, Toxicology and applied pharmacology.

[50]  O. Herbarth,et al.  Individual and combined effects of mycotoxins from typical indoor moulds. , 2013, Toxicology in vitro : an international journal published in association with BIBRA.

[51]  M. J. Silva,et al.  Multi-mycotoxin determination in baby foods and in vitro combined cytotoxic effects of aflatoxin M1 and ochratoxin A , 2013 .

[52]  H. El‐Nezami,et al.  Individual and combined cytotoxic effects of Fusarium toxins (deoxynivalenol, nivalenol, zearalenone and fumonisins B1) on swine jejunal epithelial cells. , 2013, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[53]  Rudolf Krska,et al.  LC-MS/MS-based multibiomarker approaches for the assessment of human exposure to mycotoxins , 2013, Analytical and Bioanalytical Chemistry.

[54]  L. Jacxsens,et al.  Human exposure to mycotoxins and their masked forms through cereal-based foods in Belgium. , 2013, Toxicology letters.

[55]  S. Marín,et al.  Mycotoxin bioaccessibility/absorption assessment using in vitro digestion models: a review , 2013 .

[56]  J. Leblanc,et al.  Dietary exposure to mycotoxins and health risk assessment in the second French total diet study. , 2013, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[57]  G. Font,et al.  Bioaccessibility of enniatins A, A₁, B, and B₁ in different commercial breakfast cereals, cookies, and breads of Spain. , 2013, Journal of agricultural and food chemistry.

[58]  J. Mañes,et al.  Influence of the heat treatment on the degradation of the minor Fusarium mycotoxin beauvericin , 2012 .

[59]  F. Berthiller,et al.  Masked mycotoxins: A review , 2012, Molecular nutrition & food research.

[60]  C. V. Van Peteghem,et al.  A direct assessment of mycotoxin biomarkers in human urine samples by liquid chromatography tandem mass spectrometry. , 2012, Analytica chimica acta.

[61]  W. Nijs,et al.  Digestibility and absorption of deoxynivalenol-3-ß-glucoside in in vitro models , 2012 .

[62]  B. Kabak,et al.  Assessment of the bioaccessibility of aflatoxins from various food matrices using an in vitro digestion model, and the efficacy of probiotic bacteria in reducing bioaccessibility , 2012 .

[63]  R. Krska,et al.  Development and validation of a rapid multi-biomarker liquid chromatography/tandem mass spectrometry method to assess human exposure to mycotoxins. , 2012, Rapid communications in mass spectrometry : RCM.

[64]  Giuseppe Caruso,et al.  Multiclass mycotoxin analysis in food, environmental and biological matrices with chromatography/mass spectrometry. , 2012, Mass spectrometry reviews.

[65]  G. Font,et al.  Study of the cytotoxic activity of beauvericin and fusaproliferin and bioavailability in vitro on Caco-2 cells. , 2012, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[66]  D. Sarigiannis,et al.  Considering the cumulative risk of mixtures of chemicals – A challenge for policy makers , 2012, Environmental Health.

[67]  R. Krska,et al.  Assessment of human deoxynivalenol exposure using an LC-MS/MS based biomarker method. , 2012, Toxicology letters.

[68]  Rolf Altenburger,et al.  Mixture toxicity revisited from a toxicogenomic perspective. , 2012, Environmental science & technology.

[69]  J. Mañes,et al.  Bioaccessibility of deoxynivalenol and its natural co-occurrence with ochratoxin A and aflatoxin B1 in Italian commercial pasta. , 2012, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[70]  M. Signorini,et al.  Exposure assessment of mycotoxins in cow's milk in Argentina. , 2012, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[71]  A. Azqueta,et al.  Ochratoxin A reduces aflatoxin B1 induced DNA damage detected by the comet assay in Hep G2 cells. , 2011, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[72]  G. Font,et al.  Toxicological interactions between the mycotoxins beauvericin, deoxynivalenol and T-2 toxin in CHO-K1 cells in vitro. , 2011, Toxicon : official journal of the International Society on Toxinology.

[73]  Veronica M T Lattanzio,et al.  Simultaneous LC–MS/MS determination of aflatoxin M1, ochratoxin A, deoxynivalenol, de-epoxydeoxynivalenol, α and β-zearalenols and fumonisin B1 in urine as a multi-biomarker method to assess exposure to mycotoxins , 2011, Analytical and bioanalytical chemistry.

[74]  J. Rubert,et al.  Rapid mycotoxin analysis in human urine: a pilot study. , 2011, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[75]  I. Oswald,et al.  Mycotoxin co-contamination of food and feed: meta-analysis of publications describing toxicological interactions , 2011 .

[76]  Carolyn Vickers,et al.  Risk assessment of combined exposure to multiple chemicals: A WHO/IPCS framework. , 2011, Regulatory toxicology and pharmacology : RTP.

[77]  D. Mcclements,et al.  In vitro human digestion models for food applications , 2011 .

[78]  K. Jahng,et al.  Quantitative determination of mycotoxins in urine by LC-MS/MS , 2010, Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment.

[79]  Oliver A.H. Jones,et al.  Systems toxicology approaches for understanding the joint effects of environmental chemical mixtures. , 2010, The Science of the total environment.

[80]  A. Soares,et al.  Toxicity of three binary mixtures to Daphnia magna: Comparing chemical modes of action and deviations from conceptual models , 2010, Environmental toxicology and chemistry.

[81]  Nelson Lima,et al.  How will climate change affect mycotoxins in food , 2010 .

[82]  P. Alvito,et al.  Occurrence of Aflatoxins and Ochratoxin A in Baby Foods in Portugal , 2010 .

[83]  A. Sips,et al.  Effects of probiotic bacteria on the bioaccessibility of aflatoxin B1 and ochratoxin A using an in vitro digestion model under fed conditions , 2009, Journal of environmental science and health. Part. B, Pesticides, food contaminants, and agricultural wastes.

[84]  E. Herman,et al.  Food contaminants : mycotoxins and food allergens , 2008 .

[85]  R. Manderville,et al.  Combined Toxic Effects of Ochratoxin A and Citrinin, In Vivo and In Vitro , 2008 .

[86]  H. Bacha,et al.  Individual and combined effects of ochratoxin A and citrinin on viability and DNA fragmentation in cultured Vero cells and on chromosome aberrations in mice bone marrow cells. , 2008, Toxicology.

[87]  A G Renwick,et al.  Risk assessment of dietary exposures to compounds that are genotoxic and carcinogenic--an overview. , 2008, Toxicology letters.

[88]  S. Dänicke,et al.  In vivo and in vitro effects of the mycotoxins zearalenone and deoxynivalenol on different non-reproductive and reproductive organs in female pigs: A review , 2007, Food additives and contaminants.

[89]  A. Ragas,et al.  Trends in human risk assessment of pharmaceuticals , 2007, Analytical and bioanalytical chemistry.

[90]  T. Massey,et al.  Aflatoxin B1-induced DNA damage and its repair. , 2006, Cancer letters.

[91]  Ting-Chao Chou,et al.  Theoretical Basis, Experimental Design, and Computerized Simulation of Synergism and Antagonism in Drug Combination Studies , 2006, Pharmacological Reviews.

[92]  R. Kendall,et al.  Comparative acute and combinative toxicity of aflatoxin B1 and fumonisin B1 in animals and human cells. , 2006, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[93]  D. Dietrich,et al.  In vitro investigation of individual and combined cytotoxic effects of ochratoxin A and other selected mycotoxins on renal cells. , 2006, Toxicology in vitro : an international journal published in association with BIBRA.

[94]  M. Jonker,et al.  Significance testing of synergistic/antagonistic, dose level‐dependent, or dose ratio‐dependent effects in mixture dose‐response analysis , 2005, Environmental toxicology and chemistry.

[95]  G. Williams,et al.  Risk assessment of DNA-reactive carcinogens in food. , 2005, Toxicology and applied pharmacology.

[96]  R. Stierum,et al.  Toxicology of chemical mixtures: a challenging quest along empirical sciences. , 2004, Environmental toxicology and pharmacology.

[97]  H. Larsen,et al.  Combined effects of selected Penicillium mycotoxins on in vitro proliferation of porcine lymphocytes , 2004, Mycopathologia.

[98]  T. Backhaus,et al.  Toxicity of a mixture of dissimilarly acting substances to natural algal communities: predictive power and limitations of independent action and concentration addition. , 2004, Environmental science & technology.

[99]  G. Speijers,et al.  Combined toxic effects of mycotoxins. , 2004, Toxicology letters.

[100]  S. Moukha,et al.  Synergistic effects of fumonisin B1 and ochratoxin A: are in vitro cytotoxicity data predictive of in vivo acute toxicity? , 2004, Toxicology.

[101]  M. Jonker,et al.  Toxicity of binary mixtures of cadmium‐copper and carbendazim‐copper to the nematode Caenorhabditis elegans , 2004, Environmental toxicology and chemistry.

[102]  R. Havenaar,et al.  Evaluation of the intestinal absorption of deoxynivalenol and nivalenol by an in vitro gastrointestinal model, and the binding efficacy of activated carbon and other adsorbent materials. , 2004, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[103]  I. Hertz-Picciotto,et al.  Risk characterisation of chemicals in food and diet. , 2003, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[104]  P. Gramatica,et al.  Joint algal toxicity of 16 dissimilarly acting chemicals is predictable by the concept of independent action. , 2003, Aquatic toxicology.

[105]  C. Wild,et al.  The toxicology of aflatoxins as a basis for public health decisions. , 2002, Mutagenesis.

[106]  E. Schoen,et al.  Statistically designed experiments in a tiered approach to screen mixtures of Fusarium mycotoxins for possible interactions. , 2002, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[107]  F. Tomás-Barberán,et al.  An in vitro method to simulate phenolic compound release from the food matrix in the gastrointestinal tract , 2002 .

[108]  A. Nafziger,et al.  Phenotyping of drug-metabolizing enzymes in adults: a review of in-vivo cytochrome P450 phenotyping probes. , 2000, Pharmacogenetics.

[109]  C. I. Bliss THE TOXICITY OF POISONS APPLIED JOINTLY1 , 1939 .

[110]  S. Loewe,et al.  Über Kombinationswirkungen , 1926, Naunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie.

[111]  L. Jacxsens,et al.  Impact of maximum levels in European legislation on exposure of mycotoxins in dried products: case of aflatoxin B1 and ochratoxin A in nuts and dried fruits. , 2015, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[112]  Maria João Silva,et al.  Role of Nanogenotoxicology Studies in Safety Evaluation of Nanomaterials , 2015 .

[113]  G. Cano-Sancho,et al.  Occurrence and exposure assessment of aflatoxins in Catalonia (Spain). , 2013, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[114]  M. Šegvić Klarić Adverse Effects Of Combined Mycotoxins / Štetni Učinci Kombiniranih Mikotoksina , 2012, Arhiv za higijenu rada i toksikologiju.

[115]  C. Leclercq,et al.  Guidance of EFSA: Use of the EFSA Comprehensive European Food Consumption Database in exposure assessment , 2011 .

[116]  Bochra Kouidhi,et al.  Cytotoxicity and genotoxicity induced by aflatoxin B1, ochratoxin A, and their combination in cultured Vero cells , 2010, Journal of biochemical and molecular toxicology.

[117]  A. Oomen,et al.  Applicability of an in vitro digestion model in assessing the bioaccessibility of mycotoxins from food. , 2005, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[118]  S. Loewe,et al.  Über Kombinationswirkungen , 2005, Naunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie.

[119]  Martha M Moore,et al.  Use of genetic toxicology information for risk assessment , 2005, Environmental and molecular mutagenesis.

[120]  T. Chou,et al.  Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. , 1984, Advances in enzyme regulation.