Gender and geographical variability in the exposure pattern and metabolism of deoxynivalenol in humans: a review

Deoxynivalenol (DON, also known as vomitoxin) is a common mycotoxin found worldwide, especially in contaminated food. DON is toxic to a variety of cells and tissues in humans. Three kinds of conjugated products (DON‐3‐glucuronide, DON‐15‐glucuronide and DON‐7‐glucuronide) can be found as major metabolites in human urine. Females and males show different patterns of exposure levels, and human exposure to DON also shows some geographical differences because of different DON levels in cereal‐based foods, food intake habits and UDP‐glucuronosyltransferase expression. Specifically, the C12, 13‐deepoxy metabolite was found predominantly in French adults but was rarely detected in UK adults. However, a cohort of Spanish individuals demonstrated even lower DON levels than the levels in the UK populations, whereas a very high DON exposure level was detected in South Africa and Linxian, China. Recent publications have further indicated that DON could be detected in the urine of pregnant women from different countries, which suggests that there is a potential risk to both mothers and foetuses. Additionally, phytochemicals have been shown to be less toxic to cells and laboratory animals in research studies and may also be used as food additives for reducing the toxic effects of DON. In this review, we provide global information on DON metabolism, human exposure and gender differences in humans. Also, control strategies for this mycotoxin are discussed. Copyright © 2016 John Wiley & Sons, Ltd.

[1]  Xiong Guo,et al.  Prevalence of Selenium, T-2 Toxin, and Deoxynivalenol in Kashin–Beck Disease Areas in Qinghai Province, Northwest China , 2016, Biological Trace Element Research.

[2]  F. Guay,et al.  The potential effects of antioxidant feed additives in mitigating the adverse effects of corn naturally contaminated with Fusarium mycotoxins on antioxidant systems in the intestinal mucosa, plasma, and liver in weaned pigs , 2016, Mycotoxin Research.

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

[4]  M. Blaszkewicz,et al.  Deoxynivalenol Exposure Assessment for Pregnant Women in Bangladesh , 2015, Toxins.

[5]  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.

[6]  J. Pestka,et al.  Murine Anorectic Response to Deoxynivalenol (Vomitoxin) Is Sex-Dependent , 2015, Toxins.

[7]  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.

[8]  G. Williamson,et al.  Cellular Asymmetric Catalysis by UDP-glucuronosyltransferase 1A8 Shows Functional Localization to the Basolateral Plasma Membrane* , 2015, The Journal of Biological Chemistry.

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

[10]  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.

[11]  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.

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

[13]  V. Lattanzio,et al.  Assessment of Mycotoxin Exposure in Côte d’ivoire (Ivory Coast) Through Multi-Biomarker Analysis and Possible Correlation with Food Consumption Patterns , 2014, Toxicology international.

[14]  A. Richardson,et al.  Annual variation of dietary deoxynivalenol exposure during years of different Fusarium prevalence: a pilot biomonitoring study , 2014, Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment.

[15]  Y. Gong,et al.  Deoxynivalenol exposure assessment in young children in Tanzania. , 2014, Molecular nutrition & food research.

[16]  V. Dohnal,et al.  Oxidative stress-mediated cytotoxicity and metabolism of T-2 toxin and deoxynivalenol in animals and humans: an update , 2014, Archives of Toxicology.

[17]  W. Bao,et al.  Deoxynivalenol induced oxidative stress and genotoxicity in human peripheral blood lymphocytes. , 2014, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

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

[19]  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.

[20]  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.

[21]  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.

[22]  E. Prantera,et al.  Exposure Assessment for Italian Population Groups to Deoxynivalenol Deriving from Pasta Consumption , 2013, Toxins.

[23]  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.

[24]  M. Manns,et al.  Gender matters: estrogen receptor alpha (ERα) and histone deacetylase (HDAC) 1 and 2 control the gender-specific transcriptional regulation of human uridine diphosphate glucuronosyltransferases genes (UGT1A). , 2013, Journal of hepatology.

[25]  S. de Saeger,et al.  Multimycotoxin analysis in urines to assess infant exposure: a case study in Cameroon. , 2013, Environment international.

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

[27]  V. V. Padma,et al.  Cytoprotective effect of epigallocatechin-3-gallate against deoxynivalenol-induced toxicity through anti-oxidative and anti-inflammatory mechanisms in HT-29 cells. , 2013, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[28]  P. Robinson,et al.  Antagonism of GxxPG fragments ameliorates manifestations of aortic disease in Marfan syndrome mice. , 2013, Human molecular genetics.

[29]  A. Richardson,et al.  The Human Fecal Microbiota Metabolizes Deoxynivalenol and Deoxynivalenol-3-Glucoside and May Be Responsible for Urinary Deepoxy-Deoxynivalenol , 2013, Applied and Environmental Microbiology.

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

[31]  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.

[32]  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.

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

[34]  C. Wild,et al.  Deoxynivalenol exposure assessment in a cohort of pregnant women from Bradford, UK , 2012, Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment.

[35]  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.

[36]  R. Krska,et al.  Hydrolytic fate of deoxynivalenol-3-glucoside during digestion , 2011, Toxicology Letters.

[37]  V. 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.

[38]  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.

[39]  L. Knudsen,et al.  Deoxynivalenol transport across the human placental barrier. , 2011, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[40]  X. Shu,et al.  A biomarker survey of urinary deoxynivalenol in China: the Shanghai Women's Health Study , 2011, Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment.

[41]  R. Tallarida,et al.  Resveratrol in combination with other dietary polyphenols concomitantly enhances antiproliferation and UGT1A1 induction in Caco-2 cells. , 2011, Life sciences.

[42]  R. Krska,et al.  Direct quantification of deoxynivalenol glucuronide in human urine as biomarker of exposure to the Fusarium mycotoxin deoxynivalenol , 2011, Analytical and bioanalytical chemistry.

[43]  J. Terao,et al.  Conjugated quercetin glucuronides as bioactive metabolites and precursors of aglycone in vivo. , 2011, Food & function.

[44]  J. Pestka Deoxynivalenol: mechanisms of action, human exposure, and toxicological relevance , 2010, Archives of Toxicology.

[45]  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.

[46]  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.

[47]  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.

[48]  V. Burley,et al.  Urine metabolite analysis as a function of deoxynivalenol exposure: an NMR-based metabolomics investigation , 2010, Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment.

[49]  D. Waxman,et al.  Sex Differences in the Expression of Hepatic Drug Metabolizing Enzymes , 2009, Molecular Pharmacology.

[50]  G. Perdew,et al.  Ligand Selectivity and Gene Regulation by the Human Aryl Hydrocarbon Receptor in Transgenic Mice , 2009, Molecular Pharmacology.

[51]  C. Klaassen,et al.  Mechanism of Gender-Divergent UDP-Glucuronosyltransferase mRNA Expression in Mouse Liver and Kidney , 2009, Drug Metabolism and Disposition.

[52]  C. Wild,et al.  Dietary wheat reduction decreases the level of urinary deoxynivalenol in UK adults , 2008, Journal of Exposure Science and Environmental Epidemiology.

[53]  B. Roelen,et al.  Exposure of Oocytes to the Fusarium Toxins Zearalenone and Deoxynivalenol Causes Aneuploidy and Abnormal Embryo Development in Pigs1 , 2007, Biology of reproduction.

[54]  C. Wild,et al.  Urinary Deoxynivalenol Is Correlated with Cereal Intake in Individuals from the United Kingdom , 2007, Environmental health perspectives.

[55]  T. Smith,et al.  The effects of feeding grains naturally contaminated with Fusarium mycotoxins with and without a polymeric glucomannan adsorbent on lactation, serum chemistry, and reproductive performance after weaning of first-parity lactating sows. , 2007, Journal of animal science.

[56]  T. Smith,et al.  Effects of feeding grains naturally contaminated with Fusarium mycotoxins with and without a polymeric glucomannan mycotoxin adsorbent on reproductive performance and serum chemistry of pregnant gilts. , 2006, Journal of animal science.

[57]  Robert M Eppley,et al.  Effects of deoxynivalenol (DON, vomitoxin) on in utero development in rats. , 2006, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[58]  S. Zeng,et al.  Quantitative regioselectivity of glucuronidation of quercetin by recombinant UDP-glucuronosyltransferases 1A9 and 1A3 using enzymatic kinetic parameters , 2005, Xenobiotica; the fate of foreign compounds in biological systems.

[59]  Robert M Eppley,et al.  Characterization of the effect of deoxynivalenol on selected male reproductive endpoints. , 2005, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[60]  Liliana Jiménez,et al.  Polyphenols: food sources and bioavailability. , 2004, The American journal of clinical nutrition.

[61]  F. Nagengast,et al.  Induction of rat hepatic and intestinal UDP-glucuronosyltransferases by naturally occurring dietary anticarcinogens. , 2003, Carcinogenesis.

[62]  K. Bock Vertebrate UDP-glucuronosyltransferases: functional and evolutionary aspects. , 2003, Biochemical pharmacology.

[63]  A. Clifford,et al.  Effect of Dietary Constituents With Chemopreventive Potential on Adduct Formation of a Low Dose of the Heterocyclic Amines PhIP and IQ and Phase II Hepatic Enzymes , 2003, Nutrition and cancer.

[64]  C. Wild,et al.  Development of a urinary biomarker of human exposure to deoxynivalenol. , 2003, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[65]  G. Williamson,et al.  Metabolism of quercetin-7- and quercetin-3-glucuronides by an in vitro hepatic model: the role of human beta-glucuronidase, sulfotransferase, catechol-O-methyltransferase and multi-resistant protein 2 (MRP2) in flavonoid metabolism. , 2003, Biochemical pharmacology.

[66]  P. van Bladeren,et al.  Regioselectivity of phase II metabolism of luteolin and quercetin by UDP-glucuronosyl transferases. , 2002, Chemical research in toxicology.

[67]  M. Manns,et al.  Developmental aspects of human hepatic drug glucuronidation in young children and adults , 2002, Gut.

[68]  M. Rooze,et al.  Skeletal deformities induced by the intraperitoneal administration of deoxynivalenol (vomitoxin) in mice , 2001, International Orthopaedics.

[69]  T. Walle,et al.  Induction of UDP-Glucuronosyltransferase UGT1A1 by the Flavonoid Chrysin in Caco-2 Cells—Potential Role in Carcinogen Bioinactivation , 2001, Pharmaceutical Research.

[70]  D. Barron,et al.  Human metabolism of dietary flavonoids: Identification of plasma metabolites of quercetin , 2001, Free radical research.

[71]  J. Pestka,et al.  The effect of vomitoxin (Deoxnivalenol) on testicular morphology, testicular spermatid counts and epididymal sperm counts in IL-6KO [B6129-IL6 [TmlKopf] (IL-6 gene deficient)] and WT [B6129F2 (wild type to B6129-IL6 with an intact IL-6 gene)] mice. , 1999, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[72]  H. Ciolino,et al.  Dietary flavonols quercetin and kaempferol are ligands of the aryl hydrocarbon receptor that affect CYP1A1 transcription differentially. , 1999, The Biochemical journal.

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

[74]  D. Veira,et al.  Excretion profiles of the mycotoxin deoxynivalenol, following oral and intravenous administration to sheep. , 1986, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[75]  R. Vesonder,et al.  Effect of deoxynivalenol (vomitoxin) on fertility, pregnancy, and postnatal development of Sprague-Dawley rats , 1985, Applied and environmental microbiology.

[76]  R. Morrissey Teratological study of Fischer rats fed diet containing added vomitoxin. , 1984, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[77]  J. Reynolds,et al.  Survey of vomitoxin-contaminated feed grains in midwestern United States, and associated health problems in swine. , 1984, Journal of the American Veterinary Medical Association.

[78]  F. Gonzalez,et al.  Xenobiotica the fate of foreign compounds in biological systems , 2017 .

[79]  H. Knutsen,et al.  Experimental study of deoxynivalenol biomarkers in urine GP/EFSA/CONTAM/2013/04 , 2015 .

[80]  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.

[81]  R. Tukey,et al.  Human UDP-glucuronosyltransferases: metabolism, expression, and disease. , 2000, Annual review of pharmacology and toxicology.

[82]  Tutel'ian Va,et al.  [Effect of dietary selenium on the activity of UDP-glucuronosyltransferases and metabolism of mycotoxin deoxynivalenol in rats]. , 1998 .

[83]  L. Kravchenko,et al.  [Effect of dietary selenium on the activity of UDP-glucuronosyltransferases and metabolism of mycotoxin deoxynivalenol in rats]. , 1998, Voprosy pitaniia.

[84]  Virda Verdina,et al.  Food and Agriculture , 1942, Nature.