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Deoxynivalenol (DON) is a frequent mycotoxin contaminant in cereal crops worldwide and can cause adverse health effects in exposed animals and humans. Since DON contamination in Bangladeshi food is unexplored, we conducted a biomonitoring study to assess DON exposure in the Bangladeshi population and compare it with that of German adults. In total 214 urines were collected, n=164 in Bangladesh and n=50 in Germany. In Bangladesh rural and urban residents of Rajshahi district provided urines in two seasons (n=69 in summer, n=95 in winter, with 62 participants enrolled in both periods). Urinary DON and its de-epoxy metabolite DOM-1 were measured by a previously validated sensitive LC-MS/MS method. In Bangladeshi urines, DON was detectable in 27% (range 0.16-1.78ng/mL) in summer and 31% (range 0.16-1.21ng/mL) in winter season. There was no significant difference at the mean DON level between season (summer 0.17±0.25ng/mL and winter 0.16±0.18ng/mL) and region (rural or urban residents). The metabolite DOM-1 was not detected in any urine from Bangladesh. In contrast, DON and DOM-1 were detected in 100% (range 0.16-38.44ng/mL) and 40% (range 0.10-0.73ng/mL), respectively, of the German urines. The mean DON level in German urines (9.02±6.84ng/mL) was about 53-fold higher than that found in Bangladeshi samples. This indicates a low and high dietary DON exposure among the adult population in Bangladesh and Germany, respectively. The biomarker concentrations found and published urinary excretion rates for DON then served to calculate the daily mycotoxin intake in both cohorts: the mean DON intake in Bangladesh being 6ng/kg b.w., and in Germany a mean of 268 and maximum intake of 975ng/kg b.w., values lower than the provisional maximum tolerable daily intake of 1μg/kg b.w. set by the WHO/JECFA., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Plants can metabolize the Fusarium mycotoxin deoxynivalenol (DON) by forming the masked mycotoxin deoxynivalenol-3-β-D-glucoside (D3G). D3G might be cleaved during digestion, thus increasing the total DON burden of an individual. Due to a lack of in vivo data, D3G has not been included in the various regulatory limits established for DON so far. The aim of our study was to contribute to the risk assessment of D3G by determination of its metabolism in pigs. Four piglets received water, D3G (116 μg/kg b.w.) and the equimolar amount of DON (75 μg/kg b.w.) by gavage on day 1, 5 and 9 of the experiment, respectively. Additionally, 15.5 μg D3G/kg b.w. were administered intravenously on day 13. Urine and feces were collected for 24 h and analyzed for DON, D3G, deoxynivalenol-3-glucuronide (DON-3-GlcA), deoxynivalenol-15-GlcA (DON-15-GlcA) and deepoxy-deoxynivalenol (DOM-1) by UHPLC-MS/MS. After oral application of DON and D3G, in total 84.8±9.7% and 40.3±8.5% of the given dose were detected in urine, respectively. The majority of orally administered D3G was excreted in form of DON, DON-15-GlcA, DOM-1 and DON-3-GlcA, while urinary D3G accounted for only 2.6±1.4%. In feces, just trace amounts of metabolites were found. Intravenously administered D3G was almost exclusively excreted in unmetabolized form via urine. Data indicate that D3G is nearly completely hydrolyzed in the intestinal tract of pigs, while the toxin seems to be rather stable after systemic absorption. Compared to DON, the oral bioavailability of D3G and its metabolites seems to be reduced by a factor of up to 2, approximately., (Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

This study reports on the detailed investigation of human deoxynivalenol (DON) and zearalenone (ZEN) in vivo metabolism through the analysis of urine samples obtained from one volunteer following a naturally contaminated diet containing 138μg DON and 10μg ZEN over a period of four days. Based on the mycotoxin intake and the concentrations of mycotoxin conjugates in urine, a mass balance was established. The average rates of DON excretion and glucuronidation were determined to be 68 and 76%, respectively. The investigation of formed glucuronides revealed DON-15-glucuronide as main conjugation product besides DON-3-glucuronide. Furthermore, for the first time in human urine a third DON-glucuronide was detected and the fate of ingested masked DON forms (3-acetyl-DON and DON-3-glucoside) was preliminary assessed. The mean excretion rate of ZEN was determined to be 9.4%. ZEN was mainly present in its glucuronide form and in some samples ZEN-14-glucuronide was directly determined 3-10h after exposure. For the first time concrete figures have become available for the excretion pattern of DON and ZEN-glucuronides throughout a day, the comparison of total DON in 24h and first morning urine samples and the urinary excretion rate of total ZEN in humans following exposure through naturally contaminated food. Therefore, valuable preliminary information has been obtained through the chosen experimental approach although the study involved only one single individual and needs to be confirmed in larger monitoring studies. The presented experiment contributes to a better understanding of human DON and ZEN in vivo metabolism and thereby supports advanced exposure and risk assessment to increase food safety and examine the relationship between these mycotoxins and potentially associated chronic diseases in the future., (Copyright © 2013 Michael Sulyok. Published by Elsevier Ireland Ltd.. All rights reserved.)

Deoxynivalenol-3-β-D-glucoside (D3G), a plant metabolite of the Fusarium mycotoxin deoxynivalenol (DON), might be hydrolyzed in the digestive tract of mammals, thus contributing to the total dietary DON exposure of individuals. Yet, D3G has not been considered in regulatory limits set for DON for foodstuffs due to the lack of in vivo data. The aim of our study was to evaluate whether D3G is reactivated in vivo by investigation of its metabolism in rats. Six Sprague-Dawley rats received water, DON (2.0 mg/kg body weight (b.w.)) and the equimolar amount of D3G (3.1 mg/kg b.w.) by gavage on day 1, 8 and 15, respectively. Urine and feces were collected for 48 h and analyzed for D3G, DON, deoxynivalenol-glucuronide (DON-GlcA) and de-epoxy deoxynivalenol (DOM-1) by a validated LC-tandem mass spectrometry (MS/MS) based biomarker method. After administration of D3G, only 3.7±0.7% of the given dose were found in urine in the form of analyzed analytes, compared to 14.9±5.0% after administration of DON, and only 0.3±0.1% were detected in the form of urinary D3G. The majority of administered D3G was recovered as DON and DOM-1 in feces. These results suggest that D3G is little bioavailable, hydrolyzed to DON during digestion, and partially converted to DOM-1 and DON-GlcA prior to excretion. Our data indicate that D3G is of considerably lower toxicological relevance than DON, at least in rats., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

The Fusarium toxin deoxynivalenol (DON) is one of the most abundant mycotoxins worldwide and poses many adverse health effects to human and animals. Consequently, regulatory limits and a provisional maximum tolerable daily intake (PMTDI) for this important type B-trichothecene were assigned. We conducted a pilot survey to investigate the level of DON exposure in Austrian adults by measurements of DON and its glucuronide conjugates (DON-GlcA's), as biomarkers of exposure, in first morning urine. The average concentration of total DON (free DON+DON-GlcA's) was estimated to be 20.4±2.4 μg L⁻¹ (max. 63 μg L⁻¹). Surprisingly, we found that one third of the volunteers (n=27) exceeded the established PMTDI when consuming regular diet. DON-GlcA's were directly quantified by LC-MS/MS and the results were compared with indirect quantification after enzymatic hydrolysis and confirmed the suitability of the direct method. Moreover, we investigated the in vivo metabolism of DON in humans and were able to determine two closely eluting DON-GlcA's in naturally contaminated urine samples for the first time. In contrast to previous findings we have tentatively identified DON-15-glucuronide as a major DON metabolite in human urine based on the analysis of these samples. About 75% of total glucuronides were derived from this metabolite while DON-3-glucuronide accounted for approximately 25%. The reported new findings clearly demonstrate the great potential of suitable biomarkers to critically assess exposure of humans and animals to DON., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Eleven pregnant sows with a body weight between 153 and 197 kg were fed a control diet (CON, 0.15 mg DON and 0.0035 mg ZON/kg diet) or a diet containing 15% of Fusarium toxin contaminated triticale (MYCO, 4.42 mg DON and 0.048 mg ZON/kg diet) in the period of day 35 and 70 of gestation. The indirect effect of feed intake was separated from the direct effects of the Fusarium toxins by the restricted feeding regimen where all sows were fed the same amount of feed (2000 g/d) over the whole study. At the end of experiment, fetuses were delivered by Caesarian section and samples of serum, bile, urine, liver, kidney and spleen of euthanatized sows and fetuses were taken to analyze the concentrations of DON, ZON and their metabolites. Feeding the Fusarium toxin contaminated diet to pregnant sows caused neither adverse effects on performance, organ weights and maintenance of pregnancy of sows nor on fetus weight and length. Furthermore, no teratogenic or embryolethal effects could be observed in the MYCO group. Hematological and clinical-chemical parameters of sows and fetuses were not affected by feeding, with the exception of significantly lower GLDH (glutamate dehydrogenase) serum activities in MYCO sows. The carry over of DON and ZON from the diet to the sow or fetus tissues was calculated by the diet ratio (sum of concentrations of all metabolites in the physiological specimen divided by the dietary toxin concentration), while the fetus ratio was evaluated by the sum of concentrations of all metabolites in the physiological specimen of the fetus divided by that of the sows. DON and deepoxy-DON were found in urine, bile, serum, liver, kidney and spleen of sows of the MYCO group, but not in the bile of fetuses (spleen not analyzed). ZON and its metabolite alpha-zearalenol (alpha-ZOL) were detected in urine and bile of sows, while all specimens of fetuses as well as serum and liver of sows were negative for ZON metabolites. The maximum diet ratios for urine and bile in sows of the MYCO group were 0.84 and 0.05 for DON metabolites and 1.2 and 3.8 for ZON metabolites, underscoring the differences in metabolism and excretion of both toxins. The maximum diet ratio of DON and deepoxy-DON into liver, kidney and spleen of MYCO sows were 0.003, 0.007 and 0.003, respectively. The maximum fetus ratio of DON and deepoxy-DON into urine, bile, serum, liver and kidney of fetuses were 0.006, 0, 0.5, 0.88, and 0.33, while the maximum placental ratio (sum of toxin concentrations in the physiological specimen of the fetus divided by the toxin serum concentration of the sow) were 0.64, 0, 0.50, 0.70 and 0.52, respectively. Therefore, it can be concluded that the developing fetus is exposed to DON between the gestation days 35 and 70 when the sows are fed a Fusarium toxin contaminated diet. ZON concentration in the MYCO diet was too low to get reliable results for fetus or placental ratios.