Comparative toxicokinetics of Fusarium mycotoxins in pigs and humans.

Mycotoxins frequently contaminate food and feed materials, posing a threat to human and animal health. Fusarium species produce important mycotoxins with regard to their occurrence and toxicity, especially deoxynivalenol (DON), fumonisin B1 (FB1), zearalenone (ZEN) and T-2 toxin (T-2). The susceptibility of an animal species towards the effects of these toxins in part depends on the absorption, distribution, metabolism and excretion (ADME processes) of these toxins from the body. For humans, in vivo information is scarce and often animal data is used for extrapolation to humans. From a kinetic and safety point of view, the pig seems to be a promising animal model to aid in the assessment of the toxicological risk of mycotoxins to humans. Qualitatively, the ADME processes seem to be quite similar between pigs and humans. In addition, similar metabolite and excretion patterns are observed, although some quantitative differences are noticed which are subject of this review. The high sensitivity of pigs towards mycotoxins and the similar kinetics are an advantage for the use of this animal species in the risk assessment of mycotoxins, and for the establishment of legal limits of mycotoxins.

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

[2]  F. Berthiller,et al.  Metabolism of Zearalenone and Its Major Modified Forms in Pigs , 2017, Toxins.

[3]  R. Krska,et al.  New insights into the human metabolism of the Fusarium mycotoxins deoxynivalenol and zearalenone. , 2013, Toxicology letters.

[4]  M. Metzler,et al.  Glucuronidation of zearalenone, zeranol and four metabolites in vitro: formation of glucuronides by various microsomes and human UDP-glucuronosyltransferase isoforms. , 2010, Molecular nutrition & food research.

[5]  Keqiu Jiang,et al.  Determination of multiple mycotoxins in paired plasma and urine samples to assess human exposure in Nanjing, China. , 2019, Environmental pollution.

[6]  F. Caloni,et al.  Evaluation of Fumonisin B1 and its metabolites absorption and toxicity on intestinal cells line caco-2 , 2002 .

[7]  S. Croubels,et al.  Biomarkers for Exposure as a Tool for Efficacy Testing of a Mycotoxin Detoxifier in Broiler Chickens and Pigs , 2019, Toxins.

[8]  P. Dilkin,et al.  Toxicokinetics and toxicological effects of single oral dose of fumonisin B1 containing Fusarium verticillioides culture material in weaned piglets. , 2010, Chemico-biological interactions.

[9]  S. Kersten,et al.  The plasma clearance of the Fusarium toxin deoxynivalenol (DON) is decreased in endotoxemic pigs. , 2012, Food and Chemical Toxicology.

[10]  C. Fæste,et al.  Prediction of deoxynivalenol toxicokinetics in humans by in vitro-to-in vivo extrapolation and allometric scaling of in vivo animal data , 2018, Archives of Toxicology.

[11]  E. Cundliffe,et al.  Inhibition at the initiation level of eukaryotic protein synthesis by T‐2 toxin , 1975, FEBS letters.

[12]  S. Dänicke,et al.  Residues of deoxynivalenol (DON) in pig tissue after feeding mash or pellet diets containing low concentrations. , 2008, Molecular nutrition & food research.

[13]  Lingli Huang,et al.  A comparison of hepatic in vitro metabolism of T-2 toxin in rats, pigs, chickens, and carp , 2011, Xenobiotica; the fate of foreign compounds in biological systems.

[14]  J. Garssen,et al.  The intestinal barrier as an emerging target in the toxicological assessment of mycotoxins , 2016, Archives of Toxicology.

[15]  Y. Schneider,et al.  Deoxynivalenol transport across human intestinal Caco-2 cells and its effects on cellular metabolism at realistic intestinal concentrations. , 2006, Toxicology letters.

[16]  Juan Carlos Moltó,et al.  Review on the toxicity, occurrence, metabolism, detoxification, regulations and intake of zearalenone: an oestrogenic mycotoxin. , 2007, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[17]  R. Corley,et al.  Disposition of T-2 toxin, a trichothecene mycotoxin, in intravascularly dosed swine , 1986 .

[18]  A. Visconti,et al.  Metabolism of zearalenone by sow intestinal mucosa in vitro. , 1987, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[19]  J. Bauer,et al.  Residue formation of fumonisin B1 in porcine tissues , 2003, Food additives and contaminants.

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

[21]  J. Pestka,et al.  Toxicology of deoxynivalenol (vomitoxin). , 1996, Journal of toxicology and environmental health.

[22]  M. Metzler,et al.  Aromatic hydroxylation is a major metabolic pathway of the mycotoxin zearalenone in vitro. , 2009, Molecular nutrition & food research.

[23]  R. Krska,et al.  Investigation of the hepatic glucuronidation pattern of the Fusarium mycotoxin deoxynivalenol in various species. , 2012, Chemical research in toxicology.

[24]  V. Vandenbroucke,et al.  Toxicokinetic study and absolute oral bioavailability of deoxynivalenol, T-2 toxin and zearalenone in broiler chickens. , 2013, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[25]  H. Pettersson,et al.  Lack of de-epoxidation of type B trichothecenes in incubates with human faeces , 2003, Food additives and contaminants.

[26]  H. J. Fels-Klerx Occurrence data of trichothecene mycotoxins T‐2 toxin and HT‐2 toxin in food and feed , 2010 .

[27]  S. Uhlig,et al.  Fast and sensitive LC–MS/MS method measuring human mycotoxin exposure using biomarkers in urine , 2014, Archives of Toxicology.

[28]  D. Deforce,et al.  The Ontogeny of Cytochrome P450 Enzyme Activity and Protein Abundance in Conventional Pigs in Support of Preclinical Pediatric Drug Research , 2018, Front. Pharmacol..

[29]  M. Gareis,et al.  In vitro transformation of the Fusarium mycotoxins deoxynivalenol and zearalenone by the normal gut microflora of pigs. , 1994, Natural toxins.

[30]  R. Hartley,et al.  Toxic Metabolites of Aspergillus Flavus , 1963, Nature.

[31]  F. Tashiro,et al.  The cytochrome P-450-dependent hydroxylation of T-2 toxin in various animal species. , 1987, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[32]  D. Deforce,et al.  Characterization of Porcine Hepatic and Intestinal Drug Metabolizing CYP450: Comparison with Human Orthologues from A Quantitative, Activity and Selectivity Perspective , 2019, Scientific Reports.

[33]  L. Murphy,et al.  Measurement of the relative binding affinity of zearalenone, alpha-zearalenol and beta-zearalenol for uterine and oviduct estrogen receptors in swine, rats and chickens: an indicator of estrogenic potencies. , 1989, Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology.

[34]  J. Fink-Gremmels,et al.  Bioactivation of zearalenone by porcine hepatic biotransformation. , 2005, Veterinary research.

[35]  S. Dänicke,et al.  Kinetics and metabolism of zearalenone in young female pigs. , 2005, Journal of animal physiology and animal nutrition.

[36]  M. Savard,et al.  Pharmacokinetic fate of 14C-labelled fumonisin B1 in swine. , 1994, Natural toxins.

[37]  F. Raimondi,et al.  Absorption of fumonisin B1 and aminopentol on an in vitro model of intestinal epithelium; the role of P-glycoprotein. , 2005, Toxicon : official journal of the International Society on Toxinology.

[38]  H. Trenholm,et al.  EFFECT OF DEOXYNIVALENOL (DON)-CONTAMINATED DIET FED TO GROWING-FINISHING PIGS ON THEIR PERFORMANCE AT MARKET WEIGHT, NITROGEN RETENTION AND DON EXCRETION , 1986 .

[39]  M. Bialer,et al.  Metabolism and pharmacokinetics of T-2 toxin and related trichothecenes. , 1993, Drug metabolism reviews.

[40]  M. Swindle,et al.  Animal models of toxicology testing: the role of pigs , 2013, Expert opinion on drug metabolism & toxicology.

[41]  S. Dänicke,et al.  On the effects of deoxynivalenol (DON) in pig feed on growth performance, nutrients utilization and DON metabolism , 2004 .

[42]  K. Brüssow,et al.  On the effects of graded levels of Fusarium toxin contaminated wheat in diets for gilts on feed intake, growth performance and metabolism of deoxynivalenol and zearalenone. , 2005, Molecular nutrition & food research.

[43]  D. Veira,et al.  Plasma pharmacokinetics of the mycotoxin deoxynivalenol following oral and intravenous administration to sheep. , 1985, Journal of environmental science and health. Part. B, Pesticides, food contaminants, and agricultural wastes.

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

[45]  G. Eriksen,et al.  Absorption, metabolism and excretion of 3-acetyl don in pigs , 2003, Archiv fur Tierernahrung.

[46]  S. Croubels,et al.  Impact of Subacute Exposure to T-2 Toxin and Zearalenone on the Pharmacokinetics of Midazolam as CYP3A Probe Drug in a Porcine Animal Model: A Pilot Study , 2019, Front. Pharmacol..

[47]  S. de Saeger,et al.  Mycotoxin Biomarkers of Exposure: A Comprehensive Review. , 2018, Comprehensive reviews in food science and food safety.

[48]  F. Raimondi,et al.  In vitro Study With Caco-2 Cells on Fumonisin B1: Aminopentol Intestinal Passage and Role of P-Glycoprotein , 2005, Veterinary Research Communications.

[49]  C. J. Mirocha,et al.  Distribution of tritium-labeled T-2 toxin in swine. , 1979, Journal of agricultural and food chemistry.

[50]  Sarah De Saeger,et al.  Occurrence of mycotoxins in feed as analyzed by a multi-mycotoxin LC-MS/MS method. , 2010, Journal of agricultural and food chemistry.

[51]  M. Metzler,et al.  Absorption and metabolism of the mycotoxin zearalenone and the growth promotor zeranol in Caco-2 cells in vitro. , 2011, Molecular nutrition & food research.

[52]  Suxia Zhang,et al.  Toxicokinetics of HT-2 Toxin in Rats and Its Metabolic Profile in Livestock and Human Liver Microsomes. , 2018, Journal of agricultural and food chemistry.

[53]  K. Savolainen,et al.  A review of the toxic effects and mechanisms of action of fumonisin B1 , 2008, Human & experimental toxicology.

[54]  R. Krska,et al.  Metabolism of the masked mycotoxin deoxynivalenol-3-glucoside in rats , 2012, Toxicology letters.

[55]  S. Dänicke,et al.  Kinetics and metabolism of the Fusarium toxin deoxynivalenol in farm animals: consequences for diagnosis of exposure and intoxication and carry over. , 2013, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[56]  Jia Chen,et al.  The roles of carboxylesterase and CYP isozymes on the in vitro metabolism of T-2 toxin , 2015, Military Medical Research.

[57]  E. Verbrugghe,et al.  Porcine intestinal epithelial barrier disruption by the Fusarium mycotoxins deoxynivalenol and T-2 toxin promotes transepithelial passage of doxycycline and paromomycin , 2012, BMC Veterinary Research.

[58]  H. Vesper,et al.  Acylation of Naturally Occurring and Synthetic 1-Deoxysphinganines by Ceramide Synthase , 1998, The Journal of Biological Chemistry.

[59]  P. Zöllner,et al.  Concentration levels of zearalenone and its metabolites in urine, muscle tissue, and liver samples of pigs fed with mycotoxin-contaminated oats. , 2002, Journal of agricultural and food chemistry.

[60]  H. Trenholm,et al.  Biliary excretion and enterohepatic cycling of zearalenone in immature pigs. , 1993, Toxicology and applied pharmacology.

[61]  J. Pestka Deoxynivalenol: Toxicity, mechanisms and animal health risks , 2007 .

[62]  C. Forsberg,et al.  Microbial transformation of deoxynivalenol (vomitoxin) , 1992, Applied and environmental microbiology.

[63]  J. Fink-Gremmels,et al.  Species differences in the hepatic biotransformation of zearalenone. , 2006, Veterinary journal.

[64]  S. Lecoeur,et al.  Epithelial transport of deoxynivalenol: involvement of human P-glycoprotein (ABCB1) and multidrug resistance-associated protein 2 (ABCC2). , 2007, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[65]  H. R. Burmeister,et al.  Pharmacokinetics of the trichothecene mycotoxin, T-2 toxin, in swine and cattle. , 1986, Toxicon : official journal of the International Society on Toxinology.

[66]  R. Gehring,et al.  Insights into In Vivo Absolute Oral Bioavailability, Biotransformation, and Toxicokinetics of Zearalenone, α-Zearalenol, β-Zearalenol, Zearalenone-14-glucoside, and Zearalenone-14-sulfate in Pigs. , 2019, Journal of agricultural and food chemistry.

[67]  P. Horn,et al.  In vitro microbial metabolism of fumonisin B1 , 2007, Food additives and contaminants.

[68]  J. O'kelly,et al.  Toxicity associated with Certain Samples of Groundnuts , 1961, Nature.

[69]  F. Berthiller,et al.  In vivo contribution of deoxynivalenol-3-β-d-glucoside to deoxynivalenol exposure in broiler chickens and pigs: oral bioavailability, hydrolysis and toxicokinetics , 2017, Archives of Toxicology.

[70]  R. Krska,et al.  Urinary analysis reveals high deoxynivalenol exposure in pregnant women from Croatia. , 2013, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[71]  M. Metzler,et al.  Zearalenone and its metabolites as endocrine disrupting chemicals , 2010 .

[72]  M. Churchwell,et al.  Metabolism and pharmacokinetics of zearalenone following oral and intravenous administration in juvenile female pigs. , 2017, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[73]  E. Jeffery,et al.  Lack of hepatic microsomal metabolism of deoxynivalenol and its metabolite, DOM-1. , 1987, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[74]  C. Fæste,et al.  Correction to Enzyme-Assisted Synthesis and Structural Characterization of the 3-, 8-, and 15-Glucuronides of Deoxynivalenol. , 2016, Journal of agricultural and food chemistry.

[75]  S. Isukapalli,et al.  Physiologically-Based Toxicokinetic Modeling of Zearalenone and Its Metabolites: Application to the Jersey Girl Study , 2014, PloS one.

[76]  S. El-Kafrawy,et al.  Characterisation of aflatoxin and deoxynivalenol exposure among pregnant Egyptian women , 2012, Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment.

[77]  M. Delaforge,et al.  ABCC1, ABCC2 and ABCC3 are implicated in the transepithelial transport of the myco-estrogen zearalenone and its major metabolites. , 2009, Toxicology letters.

[78]  G. Eriksen,et al.  Transformation of Trichothecenes in Ileal Digesta and Faeces from Pigs , 2002, Archiv fur Tierernahrung.

[79]  J. Bennett,et al.  Mycotoxins , 2003, Clinical Microbiology Reviews.

[80]  S. Kersten,et al.  Studies on the Bioavailability of Deoxynivalenol (DON) and DON Sulfonate (DONS) 1, 2, and 3 in Pigs Fed with Sodium Sulfite-Treated DON-Contaminated Maize , 2015, Toxins.

[81]  P. de Backer,et al.  Oral Bioavailability, Hydrolysis, and Comparative Toxicokinetics of 3-Acetyldeoxynivalenol and 15-Acetyldeoxynivalenol in Broiler Chickens and Pigs. , 2015, Journal of agricultural and food chemistry.

[82]  I. Oswald,et al.  The intestine as a possible target for fumonisin toxicity. , 2007, Molecular nutrition & food research.

[83]  S. Croubels,et al.  Toxicokinetic study and oral bioavailability of deoxynivalenol in turkey poults, and comparative biotransformation between broilers and turkeys , 2015 .

[84]  R. Corley,et al.  Glucuronide conjugates of T-2 toxin and metabolites in swine bile and urine , 1985 .

[85]  Y. Lippi,et al.  Microbial biotransformation of DON: molecular basis for reduced toxicity , 2016, Scientific Reports.

[86]  B. Fang,et al.  Liquid chromatography-tandem mass spectrometry method for toxicokinetics, tissue distribution, and excretion studies of T-2 toxin and its major metabolites in pigs. , 2014, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[87]  C. J. Mirocha,et al.  Comparative metabolism of zearalenone and transmission into bovine milk. , 1981, Food and cosmetics toxicology.

[88]  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.

[89]  Toshiyuki Fukutomi,et al.  Interactions of organic anion transporters and organic cation transporters with mycotoxins. , 2008, Journal of pharmacological sciences.

[90]  A. De Girolamo,et al.  LC-MS/MS characterization of the urinary excretion profile of the mycotoxin deoxynivalenol in human and rat. , 2011, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[91]  K. Kiessling,et al.  Plasma and Urinary Levels of Zearalenone and α-Zearalenol in a Prepubertal Gilt Fed Zearalenone , 2009 .

[92]  M. Laurentie,et al.  Risk Assessment of Deoxynivalenol by Revisiting Its Bioavailability in Pig and Rat Models to Establish Which Is More Suitable , 2015, Toxins.

[93]  Huadong Tang,et al.  Porcine Prediction of Pharmacokinetic Parameters in People: A Pig in a Poke? , 2018, Drug Metabolism and Disposition.

[94]  Jürgen B. Bulitta,et al.  Physiologically Based Pharmacokinetics of Zearalenone , 2009, Journal of toxicology and environmental health. Part A.

[95]  K. Kuča,et al.  Gender and geographical variability in the exposure pattern and metabolism of deoxynivalenol in humans: a review , 2017, Journal of applied toxicology : JAT.

[96]  R. Krska,et al.  Utilising an LC-MS/MS-based multi-biomarker approach to assess mycotoxin exposure in the Bangkok metropolitan area and surrounding provinces , 2014, Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment.

[97]  P. Horn,et al.  Distribution and elimination of fumonisin analogues in weaned piglets after oral administration of Fusarium verticillioides fungal culture , 2006, Food additives and contaminants.

[98]  S. Dänicke,et al.  Bioavailability of the Fusarium toxin deoxynivalenol (DON) from naturally contaminated wheat for the pig. , 2006, Toxicology letters.

[99]  Isabelle P. Oswald,et al.  Current Situation of Mycotoxin Contamination and Co-occurrence in Animal Feed—Focus on Europe , 2012, Toxins.

[100]  B. A. Koch,et al.  Deoxynivalenol-contaminated wheat in swine diets. , 1985, Journal of animal science.

[101]  P. Horn,et al.  Absorption, distribution and elimination of fumonisin B1 metabolites in weaned piglets , 2008, Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment.

[102]  Jae-Hyuk Yu,et al.  Occurrence, Toxicity, and Analysis of Major Mycotoxins in Food , 2017, International journal of environmental research and public health.

[103]  C. Wild,et al.  Assessment of deoxynivalenol metabolite profiles in UK adults. , 2011, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[104]  F. Berthiller,et al.  Metabolism of the masked mycotoxin deoxynivalenol-3-glucoside in pigs. , 2014, Toxicology letters.

[105]  Suxia Zhang,et al.  Metabolism of T-2 Toxin in Farm Animals and Human In Vitro and in Chickens In Vivo Using Ultra High-Performance Liquid Chromatography- Quadrupole/Time-of-Flight Hybrid Mass Spectrometry Along with Online Hydrogen/Deuterium Exchange Technique. , 2017, Journal of agricultural and food chemistry.

[106]  J. Miller,et al.  Disposition of 14C-derived residues in tissues of pigs fed radiolabelled fumonisin B1. , 1996, Food Additives and Contaminants.

[107]  C. Wannop Turkey "X" disease. , 1961 .

[108]  R. Krska,et al.  In vitro glucuronidation kinetics of deoxynivalenol by human and animal microsomes and recombinant human UGT enzymes , 2014, Archives of Toxicology.

[109]  M. Ganter,et al.  On the effectiveness of a detoxifying agent in preventing fusario-toxicosis in fattening pigs , 2004 .

[110]  Jun Jiang,et al.  Integrated Transcriptional and Proteomic Analysis with In Vitro Biochemical Assay Reveal the Important Role of CYP3A46 in T-2 Toxin Hydroxylation in Porcine Primary Hepatocytes* , 2011, Molecular & Cellular Proteomics.

[111]  A. Solhaug,et al.  Role of P-glycoprotein in deoxynivalenol-mediated in vitro toxicity. , 2018, Toxicology letters.

[112]  H. Trenholm,et al.  Nonaccumulation of Residues in Swine Tissue Following Extended Consumption of Deoxynivalenol‐Contaminated Diets , 1992 .

[113]  C. V. Van Peteghem,et al.  Study of the gastrointestinal biotransformation of zearalenone in a Caco‐2 cell culture system with liquid chromatographic methods , 2008, Journal of applied toxicology : JAT.

[114]  C. Wild,et al.  A comparison of deoxynivalenol intake and urinary deoxynivalenol in UK adults , 2010, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[115]  A. Mally,et al.  Biomonitoring of the mycotoxin Zearalenone: current state-of-the art and application to human exposure assessment , 2016, Archives of Toxicology.

[116]  A. Merrill,et al.  Inhibition of sphingolipid biosynthesis by fumonisins. Implications for diseases associated with Fusarium moniliforme. , 1991, The Journal of biological chemistry.

[117]  F. Clubb,et al.  Swine as Models in Biomedical Research and Toxicology Testing , 2012, Veterinary pathology.

[118]  Y. Ueno,et al.  Toxicological features of T-2 toxin and related trichothecenes. , 1984, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[119]  E. Franke,et al.  Pathology of the Effect of the Laser Beam on the Skin , 1963, Nature.

[120]  S. Gregory,et al.  The kinetics of urinary fumonisin B1 excretion in humans consuming maize-based diets. , 2012, Molecular nutrition & food research.

[121]  J. Fisher,et al.  Determinants of urinary deoxynivalenol and de-epoxy deoxynivalenol in male farmers from Normandy, France. , 2010, Journal of agricultural and food chemistry.

[122]  G. Schatzmayr,et al.  Mycotoxin occurrence in feed and feed raw materials worldwide: long-term analysis with special focus on Europe and Asia. , 2013, Journal of the science of food and agriculture.

[123]  G. Breves,et al.  Oral and Intravenous Fumonisin Exposure in Pigs—A Single-Dose Treatment Experiment Evaluating Toxicokinetics and Detoxification , 2018, Toxins.

[124]  S. Dänicke,et al.  On the toxicokinetics and the metabolism of deoxynivalenol (don) in the pig , 2004, Archives of animal nutrition.

[125]  Suxia Zhang,et al.  T-2 toxin, a trichothecene mycotoxin: review of toxicity, metabolism, and analytical methods. , 2011, Journal of agricultural and food chemistry.

[126]  Xiaohu Ge,et al.  The catalytic activity of cytochrome P450 3A22 is critical for the metabolism of T-2 toxin in porcine reservoirs , 2010 .

[127]  P. Gervasi,et al.  Xenobiotic metabolizing cytochrome P450 in pig, a promising animal model. , 2011, Current drug metabolism.

[128]  P. Scott,et al.  Mycotoxins in breakfast cereals from the Canadian retail market: A 3-year survey , 2008, Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment.

[129]  E. Wick,et al.  Aflatoxins B and G , 1963 .

[130]  Y. Sugita‐Konishi,et al.  The effect of naringenin on the fate and disposition of deoxynivalenol in piglets. , 2010, The Journal of veterinary medical science.

[131]  J. Miller,et al.  Pharmacokinetic fate of 14C-labeled deoxynivalenol in swine. , 1988, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[132]  S. Kersten,et al.  Bioavailability of the Fusarium toxin deoxynivalenol (DON) from wheat straw and chaff in pigs , 2013, Archives of animal nutrition.

[133]  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.

[134]  A. Visconti,et al.  Validation study on urinary biomarkers of exposure for aflatoxin B1, ochratoxin A, fumonisin B1, deoxynivalenol and zearalenone in piglets , 2013 .

[135]  H. Trenholm,et al.  Tissue distribution of deoxynivalenol in swine dosed intravenously , 1991 .

[136]  Y. Ueno Mode of action of trichothecenes , 1977, Annales de la nutrition et de l'alimentation.