New insights into the human metabolism of the Fusarium mycotoxins deoxynivalenol and zearalenone

Abstract

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.

Intestinal toxicity of the masked mycotoxin deoxynivalenol-3-β-d-glucoside

“…Indeed, following oral administration, only small percentage of applied dose of D3G was found in urine in rats and piglets (Nagl et al 2012(Nagl et al , 2014. Moreover, in a human volunteer consuming a diet naturally contaminated with D3G, the masked mycotoxin could not be detected in urine (Warth et al 2013). Interestingly, De Nijs et al (2012 observed that D3G is less absorbed by human intestinal Caco-2 cells than DON.…”

A comparative study of the human urinary mycotoxin excretion patterns in Bangladesh, Germany, and Haiti using a rapid and sensitive LC-MS/MS approach

“…Table 4 summarizes underlying excretion rates and references. Concerning the excretion of DON, we assumed an excretion rate of 68 % where 52 % were excreted as DON-GlcA and 16 % as unmetabolized DON (Warth et al 2013a). PDI was calculated using Formula 1.…”

“…No TDI for AFB 1 is set due to its carcinogenicity and its metabolites in the present study may be attributed to the high LOD of our current approach, which compromised detection at lower ranges but achieved direct assessment of multiple mycotoxins. This was also discussed by Warth et al (2013a) detecting only ZEA and no other metabolites after enzymatic treatment of the urine samples of a human volunteer consuming a ZEA containing diet. Nevertheless, the present method detects ZEA and its metabolites in concentrations that would result in PDI values exceeding the TDI.…”

Urine and serum biomonitoring of exposure to environmental estrogens II: Soy isoflavones and zearalenone in pregnant women

“…Biotransformation studies in animals reveal several pathways, including reduction of the keto group by hydroxysteroid dehydrogenases to a-and b-ZEL, cytochrome P450-catalyzed hydroxylation on aromatic and aliphatic positions, and Phase II conjugation to glucuronides and sulfates (Metzler et al, 2010). Two studies, each in a single man, reported the pattern of urinary metabolites after ingestion of either a high dose of ZEN or naturally contaminated corn-based food (Mirocha et al, 1981;Warth et al, 2013). Urinary excretion accounts for approximately 10% of the administered dose, with glucuronides of ZEN and a-ZEL as the main metabolites and minor amounts of b-ZEL.…”