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14 pages, 1284 KiB

Open AccessArticle

Development of a Generic PBK Model for Human Biomonitoring with an Application to Deoxynivalenol

by Sylvia Notenboom, Rudolf T. Hoogenveen, Marco J. Zeilmaker, Annick D. Van den Brand, Ricardo Assunção and Marcel J. B. Mengelers

Toxins 2023, 15(9), 569; https://doi.org/10.3390/toxins15090569 - 13 Sep 2023

Viewed by 910

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Human Biomonitoring and Risk Assessment of Mycotoxins)

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21 pages, 1574 KiB

Open AccessEditor’s ChoiceArticle

Providing Biological Plausibility for Exposure–Health Relationships for the Mycotoxins Deoxynivalenol (DON) and Fumonisin B1 (FB1) in Humans Using the AOP Framework

by Annick D. van den Brand, Lola Bajard, Inger-Lise Steffensen, Anne Lise Brantsæter, Hubert A. A. M. Dirven, Jochem Louisse, Ad Peijnenburg, Sophie Ndaw, Alberto Mantovani, Barbara De Santis and Marcel J. B. Mengelers

Toxins 2022, 14(4), 279; https://doi.org/10.3390/toxins14040279 - 13 Apr 2022

Cited by 7 | Viewed by 3812

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Human Biomonitoring and Risk Assessment of Mycotoxins)

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16 pages, 948 KiB

Open AccessArticle

Super-Sensitive LC-MS Analyses of Exposure Biomarkers for Multiple Mycotoxins in a Rural Pakistan Population

by Lei Xia, Hifza Rasheed, Michael N. Routledge, Hang Wu and Yun Yun Gong

Toxins 2022, 14(3), 193; https://doi.org/10.3390/toxins14030193 - 04 Mar 2022

Cited by 8 | Viewed by 2719

Abstract

High levels of mycotoxin contamination have been reported in various food commodities in Pakistan, however, there has been no exposure assessment study using multiple mycotoxins’ biomarkers. This study aimed to simultaneously assess the exposure to the five major mycotoxins: aflatoxin B₁ (AFB [...] Read more.

High levels of mycotoxin contamination have been reported in various food commodities in Pakistan, however, there has been no exposure assessment study using multiple mycotoxins’ biomarkers. This study aimed to simultaneously assess the exposure to the five major mycotoxins: aflatoxin B₁ (AFB₁), deoxynivalenol (DON), fumonisin B₁ (FB₁), ochratoxin A (OTA) and zearalenone (ZEN) in a Pakistani population using an integrated approach of human biomonitoring. Human urine samples (n = 292) were analyzed by a super-sensitive liquid-chromatography tandem mass spectrometry (LC-MS/MS) method. Rice and wheat were also collected and analyzed for mycotoxins by the LC-MS/MS method. Food consumption data were collected using a 24 h recall method. A high prevalence of urinary AFM₁ (66%, mean ± SD 20.8 ± 41.3 pg/mL) and OTA (99%, 134.7 ± 312.0 pg/mL) were found, whilst urinary DON, FB₁ and ZEN levels were low. The probable daily intake (PDI) derived from the urinary biomarkers revealed that 89% of the participants had exposure to OTA exceeding the established tolerable daily intake (TDI = 17 ng/kg bw/day). The average PDI of AFB₁ for the studied population was 43 ng/kg bw/day, with rice as the main source of AFB₁ exposure. In summary, exposure to AFB₁ and OTA are of health concern and require further management. Full article

(This article belongs to the Special Issue Human Biomonitoring and Risk Assessment of Mycotoxins)

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15 pages, 871 KiB

Open AccessArticle

Human Biomonitoring of T-2 Toxin, T-2 Toxin-3-Glucoside and Their Metabolites in Urine through High-Resolution Mass Spectrometry

by Alfonso Narváez, Luana Izzo, Noelia Pallarés, Luigi Castaldo, Yelko Rodríguez-Carrasco and Alberto Ritieni

Toxins 2021, 13(12), 869; https://doi.org/10.3390/toxins13120869 - 05 Dec 2021

Cited by 3 | Viewed by 2773

Abstract

The metabolic profile of T-2 toxin (T-2) and its modified form T-2-3-glucoside (T-2-3-Glc) remain unexplored in human samples. Therefore, the present study aimed to investigate the presence of T-2, T-2-3-Glc and their respective major metabolites in human urine samples (n = 300) [...] Read more.

The metabolic profile of T-2 toxin (T-2) and its modified form T-2-3-glucoside (T-2-3-Glc) remain unexplored in human samples. Therefore, the present study aimed to investigate the presence of T-2, T-2-3-Glc and their respective major metabolites in human urine samples (n = 300) collected in South Italy through an ultra-high performance liquid chromatography (UHPLC) coupled to Q-Orbitrap-HRMS methodology. T-2 was quantified in 21% of samples at a mean concentration of 1.34 ng/mg Crea (range: 0.22–6.54 ng/mg Crea). Almost all the major T-2 metabolites previously characterized in vitro were tentatively found, remarking the occurrence of 3′-OH-T-2 (99.7%), T-2 triol (56%) and HT-2 (30%). Regarding T-2-3-Glc, a low prevalence of the parent mycotoxin (1%) and its metabolites were observed, with HT-2-3-Glc (17%) being the most prevalent compound, although hydroxylated products were also detected. Attending to the large number of testing positive for T-2 or its metabolites, this study found a frequent exposure in Italian population. Full article

(This article belongs to the Special Issue Human Biomonitoring and Risk Assessment of Mycotoxins)

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11 pages, 627 KiB

Open AccessArticle

Assessment of Human Exposure to Five Alternaria Mycotoxins in China by Biomonitoring Approach

by Kai Fan, Wenbo Guo, Qingwen Huang, Jiajia Meng, Qi Yao, Dongxia Nie, Zheng Han and Zhihui Zhao

Toxins 2021, 13(11), 762; https://doi.org/10.3390/toxins13110762 - 28 Oct 2021

Cited by 9 | Viewed by 2285

Abstract

This biomonitoring study was conducted to investigate the concentration levels of five Alternaria mycotoxins in urine samples from 269 healthy volunteers living in the Yangtze River Delta, China. Alternariol (AOH), alternariol monomethyl ether (AME), tenuazonic acid (TeA) and tentoxin (TEN) were detected in [...] Read more.

This biomonitoring study was conducted to investigate the concentration levels of five Alternaria mycotoxins in urine samples from 269 healthy volunteers living in the Yangtze River Delta, China. Alternariol (AOH), alternariol monomethyl ether (AME), tenuazonic acid (TeA) and tentoxin (TEN) were detected in 38.3%, 48.7%, 63.9% and 23.4% of urine samples with the concentrations ranging from 0.057 to 45.8 ng/mL, 0.020 to 0.802 ng/mL, 0.050 to 80.6 ng/mL and 0.021 to 0.939 ng/mL, respectively. Altenuene (ALT) was not detected in any urine sample. Based on the urinary concentrations, the probable daily intake (PDI) values of Alternaria mycotoxins were calculated, and 100%, 99.2–100%, 0.372% and 1.12% of participants exceeded the threshold of toxicological concern (TTC) values for AOH, AME, TeA and TEN, respectively. This study revealed high potential health risks related to the contaminations of major Alternaria mycotoxins in China and highlighted the necessity for more toxicological studies to provide better basis for further comprehensive risk assessments. Full article

(This article belongs to the Special Issue Human Biomonitoring and Risk Assessment of Mycotoxins)

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22 pages, 2774 KiB

Open AccessEditor’s ChoiceArticle

Modelling the Renal Excretion of the Mycotoxin Deoxynivalenol in Humans in an Everyday Situation

by Annick D. van den Brand, Rudolf Hoogenveen, Marcel J. B. Mengelers, Marco Zeilmaker, Gunnar S. Eriksen, Silvio Uhlig, Anne Lise Brantsæter, Hubert A. A. M. Dirven and Trine Husøy

Toxins 2021, 13(10), 675; https://doi.org/10.3390/toxins13100675 - 22 Sep 2021

Cited by 7 | Viewed by 2947

Abstract

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 [...] Read more.

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_{abs_excr}). F_{abs_excr} 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_{abs_excr}, 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. Full article

(This article belongs to the Special Issue Human Biomonitoring and Risk Assessment of Mycotoxins)

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11 pages, 2836 KiB

Open AccessArticle

Analysis of Aflatoxin Biomarkers in the Hair of Experimental Animals

by Innocent Mupunga, Ilse Janse van Rensburg, Nokuthula Luthuli, Ovokeroye A. Abafe, Leshweni J. Shai and David R. Katerere

Toxins 2021, 13(8), 570; https://doi.org/10.3390/toxins13080570 - 16 Aug 2021

Viewed by 2402

Abstract

Analysis of body fluids and tissues of aflatoxin exposed individuals for the presence of aflatoxins and aflatoxin metabolites has emerged as a reliable indicator of exposure and metabolism of aflatoxins. However, current aflatoxin biomarkers are not appropriate for investigating the long-term effects of [...] Read more.

Analysis of body fluids and tissues of aflatoxin exposed individuals for the presence of aflatoxins and aflatoxin metabolites has emerged as a reliable indicator of exposure and metabolism of aflatoxins. However, current aflatoxin biomarkers are not appropriate for investigating the long-term effects of aflatoxin exposure. In this explorative study, we investigated the analysis of hair as a complementary or alternative matrix for the assessment of biomarkers of long-term aflatoxin exposure. Three groups of guinea pigs were orally dosed with 5 ugkg⁻¹bw⁻¹, 50 ugkg⁻¹bw⁻¹, and 100 ugkg⁻¹bw⁻¹ of AFB1. Urine and hair samples were collected on days 0, 1, 2, 3, 7, 30, 60, and 90 and analysed for AFB1 and AFM1 using UHPLC-MS/MS. AFB1 and AFM1 were detected in 75% and 13.6%, respectively, of the day 1 to day 7 urine samples. AFB1 was detected in hair samples collected from day 3 up to day 60. This is the first report to confirm the deposition of AFB1 in the hair of experimental animals. These findings indicate that hair analysis has the potential to provide an accurate long-term historical record of aflatoxin exposure with potentially important implications for the field of aflatoxin biomarkers. Full article

(This article belongs to the Special Issue Human Biomonitoring and Risk Assessment of Mycotoxins)

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Review

Jump to: Research

20 pages, 1373 KiB

Open AccessReview

Current Advances, Research Needs and Gaps in Mycotoxins Biomonitoring under the HBM4EU—Lessons Learned and Future Trends

by Paula Alvito, Ricardo Manuel Assunção, Lola Bajard, Carla Martins, Marcel J. B. Mengelers, Hans Mol, Sónia Namorado, Annick D. van den Brand, Elsa Vasco, Susana Viegas and Maria João Silva

Toxins 2022, 14(12), 826; https://doi.org/10.3390/toxins14120826 - 24 Nov 2022

Cited by 5 | Viewed by 1859

Abstract

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 [...] Read more.

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 B₁ (FB₁) 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 FB₁ 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. Full article

(This article belongs to the Special Issue Human Biomonitoring and Risk Assessment of Mycotoxins)

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13 pages, 349 KiB

Open AccessReview

Mycotoxin Exposure during the First 1000 Days of Life and Its Impact on Children’s Health: A Clinical Overview

by Paula Alvito and Luís Pereira-da-Silva

Toxins 2022, 14(3), 189; https://doi.org/10.3390/toxins14030189 - 04 Mar 2022

Cited by 14 | Viewed by 4315

Abstract

The first 1000 days of life are very sensitive to any event that alters health programming, and they represent a window for intervention to improve population health. Pregnant women, fetuses, and infants are particularly vulnerable to exposure to food contaminated with mycotoxins. This [...] Read more.

The first 1000 days of life are very sensitive to any event that alters health programming, and they represent a window for intervention to improve population health. Pregnant women, fetuses, and infants are particularly vulnerable to exposure to food contaminated with mycotoxins. This review aimed to gather data from the literature on mycotoxins exposure during intrauterine life and early childhood, and associated health risks, as assessed through human biomonitoring and mycotoxins occurrence in foods, in different continents. Maternal internal exposure to aflatoxins is associated with fetal growth restriction, while exposure to fumonisins increases the risk of offspring’s neural tube defects. Mycotoxin contamination of breast milk is reported worldwide, but data on adverse effects of the lactational transfer of mycotoxins on infant health are lacking. Young children are exposed to mycotoxins through contaminated infant formulas and baby foods. Both external and internal exposure to aflatoxins and fumonisins in children are reported to be associated with growth impairment. In low-income settings, where other co-factors can affect growth, this association should be interpreted with caution. Further studies on human biomonitoring of mother–infant pairs and young children are needed to guide management strategies aiming to minimize mycotoxin exposure at critical developmental stages. Full article

(This article belongs to the Special Issue Human Biomonitoring and Risk Assessment of Mycotoxins)

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