This study presents concentrations of perfluorinated compounds in food and the dietary intake of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in The Netherlands. The concentrations ...of perfluorinated compounds in food were analyzed in pooled samples of foodstuffs randomly purchased in several Dutch retail store chains with nation-wide coverage. The concentrations analyzed for PFOS and PFOA were used to assess the exposure to these compounds in The Netherlands. As concentrations in drinking water in The Netherlands were missing for these compounds, conservative default concentrations of 7 pg/g for PFOS and 9 pg/g for PFOA, as reported by European Food Safety Authority, were used in the exposure assessment. In food, 6 out of 14 analyzed perfluorinated compounds could be quantified in the majority of the food categories (perfluoroheptanoic acid (PFHpA), PFOA, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoro-1-hexanesulfonate (PFHxS), and PFOS). The highest concentration of the sum of these six compounds was found in crustaceans (825 pg/g product, PFOS: 582 pg/g product) and in lean fish (481 pg/g product, PFOS: 308 pg/g product). Lower concentrations were found in beef, fatty fish, flour, butter, eggs, and cheese (concentrations between 20 and 100 pg/g product; PFOS, 29–82 pg/g product) and milk, pork, bakery products, chicken, vegetable, and industrial oils (concentration lower than 10 pg/g product; PFOS not detected). The median long-term intake for PFOS was 0.3 ng/kg bw/day and for PFOA 0.2 ng/kg bw/day. The corresponding high level intakes (99th percentile) were 0.6 and 0.5 ng/kg bw/day, respectively. These intakes were well below the tolerable daily intake values of both compounds (PFOS, 150 ng/kg bw/day; PFOA, 1500 ng/kg bw/day). The intake calculations quantified the contribution of drinking water to the PFOS and PFOA intake in The Netherlands. Important contributors of PFOA intake were vegetables/fruit and flour. Milk, beef, and lean fish were important contributors of PFOS intake.
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The mycotoxin deoxynivalenol (DON) was one of the priority substances in the European Joint Human Biomonitoring Initiative (HBM4EU) project. In this study, to better interpret the actual internal ...exposure of DON in the general population and safeguard public health, human biomonitoring guidance values of DON for the general population (HBM-GV
) were derived. The HBM-GV
of DON was based on either the total DON (DON and its glucuronides) or DON's main metabolite (DON-15-GlcA) levels in 24-h urine samples, resulting in a HBM-GV
of 0.023 µg/mL for the total DON or a HBM-GV
of 0.020 µg/mL for DON-15-GlcA. The use of 24-h urine samples is recommended based on the fact that DON and its metabolites have a short elimination half-life (T
), and 95% of the cumulative amount was excreted within 12 h after DON intake. The T
for DON, DON-15-GlcA, and total DON were estimated to be 2.55 h, 2.95 h, and 2.95 h, respectively. Therefore, a 24-h urine sample reflects almost all of the DON exposure from the previous day, and this type of sample was considered for the derivation of a HBM-GV
for DON.
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Humans are exposed to mycotoxins on a regular basis. Exposure to a mixture of mycotoxins may, therefore, result in a combination of adverse effects, or trigger the same effects. This should be ...accounted for when assessing the combined risk of multiple mycotoxins. Here, we show the outcome of using different approaches in assessing the risks related to the combined exposure to mycotoxins. We performed a tiered approach using assessment groups with a common target organ (kidney, liver and haematologic system), or a common adverse effect (phenomenon) (reduced white blood cell count), to combine the exposure to mycotoxins. The combined exposure was calculated for the individuals in this assessment, using the Monte Carlo Risk Assessment (MCRA) tool. The risk related to this combined exposure was assessed using toxicological reference values, e.g., health based guidance values. We show that estimating the combined risk by adding the single compounds' risk distributions slightly overestimates the combined risk in the 95th percentile, as compared to combining the exposures at an individual level. We also show that relative potency factors can be used to refine the mixture risk assessment, as compared to ratios of toxicological reference values with different effect sizes and assessment factors.
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Toxicokinetic modelling provides a powerful tool in relating internal human exposure (i.e., assessed through urinary biomarker levels) to external exposure. Chemical specific toxicokinetic models are ...available; however, this specificity prevents their application to similar contaminants or to other routes of exposure. For this reason, we investigated whether a generic physiological-based kinetic (PBK) model might be a suitable alternative for a biokinetic model of deoxynivalenol (DON). IndusChemFate (ICF) was selected as a generic PBK model, which could be fit for purpose. Being suited for simulating multiple routes of exposure, ICF has particularly been used to relate the inhalation and dermal exposure of industrial chemicals to their urinary excretion. For the first time, the ICF model was adapted as a generic model for the human biomonitoring of mycotoxins, thereby extending its applicability domain. For this purpose, chemical-specific data for DON and its metabolites were collected directly from the literature (distribution and metabolism) or indirectly (absorption and excretion) by fitting the ICF model to previously described urinary excretion data. The obtained results indicate that this generic model can be used to model the urinary excretion of DON and its glucuronidated metabolites following dietary exposure to DON. Additionally, the present study establishes the basis for further development of the model to include an inhalation exposure route alongside the oral exposure route.
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Mycotoxins are natural metabolites produced by fungi that contaminate food and feed worldwide. They can pose a threat to human and animal health, mainly causing chronic effects, e.g., immunotoxic and ...carcinogenic. Due to climate change, an increase in European population exposure to mycotoxins is expected to occur, raising public health concerns. This urges us to assess the current human exposure to mycotoxins in Europe to allow monitoring exposure and prevent future health impacts. The mycotoxins deoxynivalenol (DON) and fumonisin B
(FB
) were considered as priority substances to be studied within the European Human Biomonitoring Initiative (HBM4EU) to generate knowledge on internal exposure and their potential health impacts. Several policy questions were addressed concerning hazard characterization, exposure and risk assessment. The present article presents the current advances attained under the HBM4EU, research needs and gaps. Overall, the knowledge on the European population risk from exposure to DON was improved by using new harmonised data and a newly derived reference value. In addition, mechanistic information on FB
was, for the first time, organized into an adverse outcome pathway for a congenital anomaly. It is expected that this knowledge will support policy making and contribute to driving new Human Biomonitoring (HBM) studies on mycotoxin exposure in Europe.
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Mycotoxins are toxic secondary metabolites produced by various fungi that can contaminate food crops, which, in turn, may lead to human exposure. Chronic exposure to mycotoxins can cause adverse ...health effects including reproductive and developmental toxicity. Pregnant women and their foetuses present a vulnerable group for exposure to mycotoxins that can cross the placenta. Human biomonitoring of mycotoxins provides a real-life approach to estimate internal exposure. In this pilot study, 24-h urine samples from 36 pregnant Dutch women were analysed for aflatoxin M1 (AFM1), total deoxynivalenol (DON), de-epoxy-deoxynivalenol (DOM-1), total zearalenone (ZEN), total α-zearalenol (α-ZEL), total β-zearalenol (β-ZEL) and total zearalanone (ZAN), where ‘total’ refers to mycotoxins and their conjugated forms. Serum samples from these women were analysed for fumonisin B1 (FB1) and ochratoxin A (OTA). All samples were measured using liquid chromatography–tandem mass spectrometry (LC-MS/MS). The most prevalent mycotoxins were total DON, total ZEN and OTA, with a detection frequency of 100%. DOM-1, total α-ZEL and total β-ZEL were detected but to a lesser extent, while AFM1, total ZAN and FB1 were undetected. Median concentrations were 4.75 μg total DON/L, 0.0350 μg DOM-1/L, 0.0413 μg total ZEN/L, 0.0379 μg total α-ZEL/L, 0.0189 μg total β-ZEL/L, and 0.121 μg OTA/L. The calculated median concentration for total ZEN and its metabolites was 0.105 μg/L. Based on two separate risk assessment approaches, total DON exposure in this group was considered to be of low concern. Similarly, exposure to total ZEN and its metabolites in this group was of low concern. For OTA, the risk of non-neoplastic effects was of low concern based on exposure in this group, and the risk of neoplastic effects was of low concern in the majority of participants in this group. The findings of this pilot study confirm the presence of mycotoxins in the urine and serum of pregnant Dutch women, with total DON, total ZEN, and OTA most frequently detected. Exposure to all measured mycotoxins was considered to be of low concern in this group, except for exposure to OTA, which was of low concern for the majority of participants. The study’s findings offer valuable insights but should be confirmed using a larger and more diverse sample of the Dutch general population.
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Humans are chronically exposed to the mycotoxins deoxynivalenol (DON) and fumonisin B1 (FB1), as indicated by their widespread presence in foods and occasional exposure in the workplace. This ...exposure is confirmed by human biomonitoring (HBM) studies on (metabolites of) these mycotoxins in human matrices. We evaluated the exposure-health relationship of the mycotoxins in humans by reviewing the available literature. Since human studies did not allow the identification of unequivocal chronic health effects upon exposure to DON and FB1, the adverse outcome pathway (AOP) framework was used to structure additional mechanistic evidence from in vitro and animal studies on the identified adverse effects. In addition to a preliminary AOP for DON resulting in the adverse outcome (AO) 'reduced body weight gain', we developed a more elaborated AOP for FB1, from the molecular initiating event (MIE) 'inhibition of ceramide synthases' leading to the AO 'neural tube defects'. The mechanistic evidence from AOPs can be used to support the limited evidence from human studies, to focus FB1- and DON-related research in humans to identify related early biomarkers of effect. In order to establish additional human exposure-health relationships in the future, recommendations are given to maximize the information that can be obtained from HBM.
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A mixture risk assessment (MRA) for four metals relevant to chronic kidney disease (CKD) was performed. Dietary exposure to cadmium or lead alone exceeded the respective reference values in the ...majority of the 10 European countries included in our study. When the dietary exposure to those metals and inorganic mercury and inorganic arsenic was combined following a classical or personalised modified reference point index (mRPI) approach, not only high exposure (95th percentile) estimates but also the mean exceeded the tolerable intake of the mixture in all countries studied. Cadmium and lead contributed most to the combined exposure, followed by inorganic arsenic and inorganic mercury. The use of conversion factors for inorganic arsenic and inorganic mercury from total arsenic and total mercury concentration data was a source of uncertainty. Other uncertainties were related to the use of different principles to derive reference points. Yet, MRA at the target organ level, as performed in our study, could be used as a way to efficiently prioritise assessment groups for higher-tier MRA. Since the combined exposure to the four metals exceeded the tolerable intake, we recommend a refined MRA based on a common, specific nephrotoxic effect and relative potency factors (RPFs) based on a similar effect size.
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The dietary exposure to the mycotoxin deoxynivalenol (DON) can be assessed by human biomonitoring (HBM). Here, we assessed the relation between dietary DON intake and the excretion of its major ...metabolite DON-15-glucuronide (DON15GlcA) through time, in an everyday situation. For 49 volunteers from the EuroMix biomonitoring study, the intake of DON from each meal was calculated and the excretion of DON and its metabolites was analyzed for each urine void collected separately throughout a 24-h period. The relation between DON and DON15GlcA was analyzed with a statistical model to assess the residence time and the excreted fraction of ingested DON as DON15GlcA (f
). F
was treated as a random effect variable to address its heterogeneity in the population. The estimated time in which 97.5% of the ingested DON was excreted as DON15GlcA was 12.1 h, the elimination half-life was 4.0 h. Based on the estimated f
, the mean reversed dosimetry factor (RDF) of DON15GlcA was 2.28. This RDF can be used to calculate the amount of total DON intake in an everyday situation, based on the excreted amount of DON15GlcA. We show that urine samples collected over 24 h are the optimal design to study DON exposure by HBM.
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Quercetin is a dietary antioxidant that prevents oxidation of low-density lipoproteins in vitro. Intake of quercetin was inversely associated with coronary heart disease mortality in elderly Dutch ...men. However, the extent of absorption of quercetin in humans is unclear. The aim of this study was to quantify absorption of various forms of quercetin. Nine healthy ileostomy subjects were studied, to avoid losses caused by colonic bacteria. They followed a quercetin-free diet for 12 d; on days 4, 8, and 12 they received a supplement of fried onions at breakfast (rich in quercetin glucosides) equivalent to 89 mg aglycone, pure quercetin rutinoside (the major quercetin compound in tea) equivalent to 100 mg aglycone, or 100 mg pure quercetin aglycone, in random order. Subsequently, participants collected ileostomy effluent and urine for 13 h. In vitro incubations of quercetin or its glycosides with gastrointestinal fluids showed minimal degradation. Absorption of quercetin, defined as oral intake minus ileostomy excretion and corrected for 14% degradation within the ileostomy bag, was 52 +/- 15% for quercetin glucosides from onions, 17 +/- 15% for quercetin rutinoside, and 24 +/- 9% for quercetin aglycone. Mean excretion of quercetin or its conjugates in urine was 0.5% of the amount absorbed; quercetin excretion in urine was negatively correlated with excretion in ileostomy effluent (r = -0.78, n = 27). We conclude that humans absorb appreciable amounts of quercetin and that absorption is enhanced by conjugation with glucose.
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