Mycotoxins in blood and urine of Swedish adolescents—possible associations to food intake and other background characteristics

Mycotoxin Research https://doi.org/10.1007/s12550-019-00381-9 ORIGINAL ARTICLE Mycotoxins in blood and urine of Swedish adolescents—possible associations to food intake and other background characteristics Eva Warensjö Lemming 1 & Andrea Montano Montes 2 & Jessica Schmidt 3 & Benedikt Cramer 3 & Hans-Ulrich Humpf 3 & Lotta Moraeus 1 & Monica Olsen 1 Received: 14 August 2019 / Revised: 26 November 2019 / Accepted: 27 November 2019 # The Author(s) 2019 Abstract The exposure to mycotoxins of Swedish adolescents is currently unknown. The aim of the present study was to investigate the exposure to mycotoxins and their association with food intake, and background characteristics in adolescents of a national dietary survey. About 3000 school students (1000 from the 5th, 8th and 11th school years) were recruited for the survey. The participants completed Web-based questionnaires on food propensity, sociodemography and health, and a Web-based dietary recall. Spot urine and blood samples were collected from 1105 of the participants for mycotoxin biomarker analysis. Mycotoxins were analysed with multibiomarker methods in urine (HPLC-MS/MS) and serum (HPLC-MS/MS). Of the 35 different analytes in urine, the frequency of positive samples were the following: deoxynivalenol (DON, 4.8%), DON-15-β-D-O-glucuronide (DON-15GlcA, 9.1%), dihydro-citrinone (DH-CIT, 0.5%), HT-2-glucuronide (HT-2-3-GlcA, 0.1%) and ochratoxin A (OTA, 0.1%). Of the 27 different analytes in serum, OTA was detected in all samples, while 2’R-ochratoxin A (2’R-OTA) was found in 8.3% and enniatin B (EnB) in 99.2% of the samples. Exposure assessment calculations were performed on OTA from the serum concentration and on DON equivalents (DON eqv) from the urine concentration. All probable daily intake (PDI) estimates were below tolerable daily intakes, except for 1.6% of the participants for DON. The maximum PDI was 4.3 μg DON eqv/kg body weight and day. Consumption of cereal grain commodities was associated with levels of DON, EnB or OTA in biofluids. Serum OTAwas also associated with intakes of raisins and coffee. Furthermore, coffee consumption correlated well with 2’R-OTA concentration in serum. In conclusion, exposure to mycotoxins in Swedish adolescents is common, but fortunately, high exposure was rare. Keywords Deoxynivalenol . Ochratoxin A . 2’R-ochratoxin A . Enniatin B . Dietary recall Introduction Humans are exposed to multiple mycotoxins via food consumption and from the environment, usually by occupational Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12550-019-00381-9) contains supplementary material, which is available to authorized users. * Eva Warensjö Lemming 1 Risk Benefit Assessment Department, Swedish Food Agency, PO Box 622, 75126 Uppsala, Sweden 2 Karolinska institute, Institute of Environmental Medicine, Box 210, 171 77 Stockholm, Sweden 3 Westfälische Wilhelms-Universität Münster, Institute of Food Chemistry, Corrensstr. 45, 48149 Münster, Germany exposure. The most important route of exposure of the general population is intake of contaminated foods and the most frequently detected mycotoxins are deoxynivalenol (DON) and ochratoxin A (OTA) (Ali et al. 2016; Heyndrickx et al. 2015; Märtlbauer et al. 2009; Solfrizzo et al. 2014; Wallin et al. 2015; Viegas et al. 2019). In addition to OTA, the isomer 2’R-ochratoxin A (2’R-OTA), which is formed during thermal processing of coffee, is of relevance since it was previously found in all blood samples of coffee drinkers in average half the concentration of OTA (Cramer et al. 2015). Besides contaminated food samples, exposure can also occur by inhalation of bioaerosols and organic dust or by dermal contact (Degen 2011). In risk assessment of mycotoxins, food consumption data and occurrence data from the corresponding foods are normally used to estimate population exposure. However, such method cannot estimate the individual intake and hence biomarker-based methods are more and more used to assess dietary exposure from blood or urine concentrations. This includes the detection Mycotoxin Res of the parent compounds (mycotoxins) and/or their main phase I and phase II metabolites (e.g. glucuronide or sulphate conjugates). Another advantage is that biomarker-based methods include all sources of exposure. Human biomonitoring in combination with dietary surveys can be a useful tool to confirm exposure of mycotoxins, to correlate exposure to certain food intake and to perform trend analyses. In addition, it can be an important tool to reveal influence of other factors such as differences in exposure due to socioeconomic or regional factors (Ali et al. 2016; Breitholtz et al. 1991; Chen et al. 2017; Mitropoulou et al. 2018; Pacin et al. 2008). However, despite those benefits, human biomonitoring is more useful in human health and dietary studies, than its use in exact exposure assessment of daily intake. Until now, exposure assessment of daily intake from blood or urine concentration remains difficult, unless the human toxicokinetics and inter-individual differences are better understood (Ali et al. 2016; Dietrich et al. 2005; Duarte et al. 2011). Of the mycotoxins of interest, DON is rapidly absorbed, distributed, metabolized and excreted. DON-15-glucuronide (DON-15-GlcA) is the most prominent proposed metabolite of DON, followed by DON-3-glucuronide (DON-3-GlcA) with a constant ratio around 4/1 DON-15-GlcA/DON-3GlcA (Vidal et al. 2018). However, we must mention that the structure of DON-15-GlcA has not been fully elucidated as no NMR data have been published, yet. The mean excretion rate of total DON, as free DON and phase I and II metabolites, was recently compiled by (Faeste et al. 2018) and a mean excretion ratio of 70% was derived. De-epoxy-DON (DOM1) has also been detected in human urine (Heyndrickx et al. 2015; Mitropoulou et al. 2018) but not consistently (Papageorgiou et al. 2018). DOM-1 is a detoxification product formed by the gut microbiota (Gratz et al. 2013) which also can epimerize DON to 3-epi-DON. In contrast to DON, the toxicokinetics of OTA is complex. There are big differences between species, and human studies reveal that there are high inter- and intra-individual variations in the metabolism and excretion of OTA (O'Brien et al. 2001; Studer-Rohr et al. 2000). Following a human study, a twocompartment toxicokinetic profile was proposed. In the model, a fast distribution and elimination phase is followed by a second slower elimination phase, resulting in an elimination half-life of 35 days (Studer-Rohr et al. 2000). The Swedish Food Agency has previously published an extended evaluation of urinary multi-biomarker analysis of mycotoxins and metabolites among adults (n = 250) and in school children (n = 50) in the 5th school year (Mitropoulou et al. 2018). DON and OTA were the most commonly occurring mycotoxins in urine of both a d u l t s a n d c h i l d r e n . B e s i d e s O T (...truncated)