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Background: Mycotoxins are toxic fungal secondary metabolites that contaminate a wide spectrum of essential foods worldwide, such as grain-based products, nuts and spices, causing adverse health effects pertaining to their carcinogenic, nephrotoxic and hepatotoxic nature, among others., Aim: The aim of this systematic review (SR) is to systematically search for, appraise and synthesize primary research evidence to identify what is known about dietary mycotoxin-related health effects and what remains unknown, as well as the uncertainty around findings and the recommendations for the future., Search Strategy and Eligibility Criteria: Search strategies, as well as eligibility criteria were structured according to a predefined PECO (population, exposure, comparison, and outcome) research question and developed in an iterative scoping process. Several bibliographic databases, including Embase, Cochrane Library, Pubmed, Web of Science Core Collection and Scopus, will be searched. Primary research on any measured or modelled dietary exposure to a single or multiple mycotoxins, and adverse human health outcomes (i.e. cancer, non-carcinogenic diseases, and reproductive & developmental adverse outcomes) will be included, and references will be imported into Covidence. In vitro, ex vivo, in silico, animal and review studies, as well as expert's opinions, secondary literature, conference abstracts, presentations, posters, book chapters, dissertations and studies involving non-dietary mycotoxin exposure, will be excluded., Study Selection: Two independent reviewers will screen titles and abstracts, and review full-texts. Any disagreements will be resolved by a third reviewer based on two-third majority., Data Extraction: Data from retained eligible studies will be extracted by the principal reviewer, and peer-checked by a second reviewer., Study Quality Assessment: Eligible studies will be evaluated for risk of bias (Overall High-Quality Assessment Tool, OHAT) and certainty of evidence (Grading of Recommendations Assessment, Development and Evaluation, GRADE)., Evidence Synthesis: A detailed summary of the included studies will be provided within a tabular format and narratively discussed. Heat maps will be constructed to provide information on available knowledge (gaps), and a meta-analysis may be performed based on the variability in predefined PECO elements and depending on the heterogeneity of studies., Conclusion: This protocol describes the methodology for the conduct of a SR on mycotoxin-related human health risks, that could guide future research and inform regulatory decisions, as emphasized by the European Commission within the field of regulatory risk assessment for emerging chemicals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Deoxynivalenol (DON) is a mycotoxin frequently observed in cereals and cereal-based foods, with reported toxicological effects including reduced body weight, immunotoxicity and reproductive defects. The European Food Safety Authority used traditional risk assessment approaches to derive a deterministic Tolerable Daily Intake (TDI) of 1 μg/kg-day, however data from human biomarkers studies indicate widespread and variable exposure worldwide, necessitating more sophisticated and advanced methods to quantify population risk. The World Health Organization/International Programme on Chemical Safety (WHO/IPCS) has previously used DON as a case example in replacing the TDI with a probabilistic toxicity value, using default uncertainty and variability distributions to derive the Human Dose corresponding to an effect size M in the I th percentile of the population (HD M ) for M = 5 % decrease in body weight and I = 1 %. In this study, we extend this case study by incorporating (1) Bayesian modeling approaches, (2) using both in vivo data and in vitro population new approach methods to replace default distributions for interspecies toxicokinetic (TK) differences and intraspecies TK and toxicodynamic (TD) variability, and (3) integrating biomonitoring data and probabilistic dose-response functions to characterize population risk distributions. We first derive an HD I ) for M = 5 % decrease in body weight and I = 1 %. In this study, we extend this case study by incorporating (1) Bayesian modeling approaches, (2) using both in vivo data and in vitro population new approach methods to replace default distributions for interspecies toxicokinetic (TK) differences and intraspecies TK and toxicodynamic (TD) variability, and (3) integrating biomonitoring data and probabilistic dose-response functions to characterize population risk distributions. We first derive an HD M I of 5.5 [1.4-24] μg/kg-day, also using TK modeling to converted the HD M I of 3.9 [1.0-16] μg/kg-day. We then illustrate how this integrative approach can advance quantitative risk characterization using two human biomonitoring datasets, estimating both the fraction of population with an effect size M ≥ 5 % as well as the distribution of effect sizes. Overall, we demonstrate that integration of Bayesian modeling, human biomonitoring data, and in vitro population-based TD data within the WHO/IPCS probabilistic framework yields more accurate, precise, and comprehensive risk characterization.M I for comparison with biomonitoring data, with a blood BE M I of 0.53 [0.17-1.6] μg/L and a urinary excretion BE M I of 3.9 [1.0-16] μg/kg-day. We then illustrate how this integrative approach can advance quantitative risk characterization using two human biomonitoring datasets, estimating both the fraction of population with an effect size M ≥ 5 % as well as the distribution of effect sizes. Overall, we demonstrate that integration of Bayesian modeling, human biomonitoring data, and in vitro population-based TD data within the WHO/IPCS probabilistic framework yields more accurate, precise, and comprehensive risk characterization., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Weihsueh Chiu reports financial support was provided by National Institute of Environmental Health Sciences. Ivan Rusyn reports financial support was provided by National Institute of Environmental Health Sciences. Weihsueh Chiu reports financial support was provided by United States Environmental Protection Agency. Ivan Rusyn reports financial support was provided by United States Environmental Protection Agency. Marthe De Boevre reports financial support was provided by European Union. Weihsueh Chiu reports a relationship with Dreamtech Co Ltd that includes: consulting or advisory. The NIH Awards R41TR002567 and R42ES032642 were granted to DREAM Tech, LLC to develop and commercialize the BBMD modeling system. W.A.C. is affiliated with DREAM Tech, LLC, and may benefit from the success of the BBMD system. Other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Mycotoxin exposure during pregnancy has been associated with adverse birth outcomes in low- and middle-income countries. The evidence, however, is inconsistent and mainly limited to the assessment of a single mycotoxin. We assessed biomarkers of exposure to multiple mycotoxins during pregnancy and their associations with adverse birth outcomes in rural Ethiopia., Methods: We analyzed data from 579 pregnant women between 8 and 24 weeks of completed gestation enrolled in a prospective cohort study. Serum mycotoxin concentrations were determined using liquid chromatography coupled with tandem mass spectrometry. Multivariable linear probability models, adjusted for potential confounding factors and multiple comparisons, were fitted to assess the associations between mycotoxin exposure and small for gestational age and preterm birth. We applied principal component analysis to reduce the dimensionality of biomarker data from several taxonomic mycotoxin groups., Results: All pregnant women were co-exposed to at least five mycotoxins, and one pregnant woman was co-exposed to 27 mycotoxins. Fumonisins (FB), i.e., FB 2 , FB 3 , FB 1 , and tenuazonic acid were the most frequently identified mycotoxins in 98.8, 95.3, 93.3, and 81.4% of the samples respectively. Deoxynivalenol was detected in 38.7%, nivalenol in 50.1%, ochratoxin α in 67.9%, and zearalenone in 50.9% of the serum samples. After adjustment, we found no statistically significant (all P ≥ 0.05) associations between mycotoxin exposures and birth outcomes., Conclusions: Despite our study providing no evidence for relationships between mycotoxin biomarkers and adverse birth outcomes, our findings do indicate an extensive presence of multiple mycotoxin exposure among pregnant women. Public health policies and nutrition-sensitive interventions must ensure exposure to mycotoxins is reduced in rural Ethiopia., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

FLEXiGUT is the first large-scale exposomics study focused on chronic low-grade inflammation. It aims to characterize human life course environmental exposure to assess and validate its impact on gut inflammation and related biological processes and diseases. The cumulative influences of environmental and food contaminants throughout the lifespan on certain biological responses related to chronic gut inflammation will be investigated in two Flemish prospective cohorts, namely the "ENVIRONAGE birth cohort", which provides follow-up from gestation to early childhood, and the "Flemish Gut Flora Project longitudinal cohort", a cohort of adults. The exposome will be characterised through biomonitoring of legacy and emerging contaminants, mycotoxins and markers of air pollution, by analysing the available metadata on nutrition, location and activity, and by applying state-of-the-art -omics techniques, including metagenomics, metabolomics and DNA adductomics, as well as the assessment of telomere length and measurement of inflammatory markers, to encompass both exposure and effect. Associations between exposures and health outcomes will be uncovered using an integrated -omics data analysis framework comprising data exploration, pre-processing, dimensionality reduction and data mining, combined with machine learning-based pathway analysis approaches. This is expected to lead to a more profound insight in mechanisms underlying disease progression (e.g. metabolic disorders, food allergies, gastrointestinal cancers) and/or accelerated biological ageing., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Context: Oesophageal cancer (EC) is among the common causes of illness and death among all cancers worldwide. Advanced EC has a poor prognosis, with worse outcomes observed in low-income settings. Oesophageal squamous cell carcinoma (ESCC) is the most common EC histology reported globally, with the highest ESCC incidence rates in the 'Asian Belt' and the African EC corridor. While the aetiology of ESCC is well-documented in the 'Asian belt', data for the African EC corridor and the entirety of sub-Saharan Africa (SSA) are fewer., Objective: To help address gaps in ESCC aetiology in SSA, we critically evaluated evidence of lifestyle, environmental, and epigenetic factors associated with ESCC risk and discussed prospects of defining ESCC exposome., Data Inclusion: Unlimited English and non-English articles search were made on PubMed Central and Web of Science databases from January 1970 to August 2021. In total, we retrieved 999 articles and considered meta-analyses, case-control, and cohort studies. The quality of individual studies was assessed using the Newcastle-Ottawa scale., Data Extraction: Details extracted include the year of publication, country of origin, sample size, comparators, outcomes, study subjects, and designs., Data Analysis: Together, we assessed 13 case-control studies and two meta-analyses for the effect of lifestyle or environmental exposures on ESCC risk. Again, we evaluated seven case-control studies and one meta-analysis regarding the role of epigenetics in ESCC tumorigenesis., Results: In general, evidence of ESCC aetiology points to essential contributions of alcohol, tobacco, hot beverages, biomass fuel, and poor oral health/hygiene, although more precise risk characterisation remains necessary., Conclusion: We conclude that ESCC in SSA is a multifactorial disease initiated by several external exposures that may induce aberrant epigenetic changes. The expanding aetiological research in this domain will be enhanced by evidence synthesis from classical and molecular epidemiological studies spanning the external and internal exposome., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The European Food Consumption Validation (EFCOVAL) project includes 600 men and women from Belgium, the Czech Republic, France, the Netherlands, and Norway, who had given serum and 24-hour urine samples, and completed 24-hour dietary recall (24-HDR) interviews. Consumption, according to 24-HDR, was matched against the European Food Safety Authority (EFSA) databases of mycotoxin contaminations, via the FoodEx1 standard classifications, producing an indirect external estimate of dietary mycotoxin exposure. Direct, internal measurements of dietary mycotoxin exposure were made in serum and urine by ultra-performance liquid chromatography coupled to tandem mass spectrometry. For the first time, mycotoxin exposures were thoroughly compared between two 24-HDRs, and two 24-hour urine samples collected during the same days covered by the 24-HDRs. These measurements were compared to a single-time point serum measurement to investigate evidence of chronic mycotoxin exposure. According to 24-HDR data, all 600 individuals were exposed to between 4 and 34 mycotoxins, whereof 10 found to exceed the tolerable daily intake. Correlations were observed between two time points, and significant correlations were observed between concentrations in serum and urine. However, only acetyldeoxynivalenol, ochratoxin A, and sterigmatocystin were found to have significant positive correlations between 24-HDR exposures and serum, while aflatoxin G1 and G2, HT-2 toxin, and deoxynivalenol were associated between concurrent 24-HDR and 24-hour urine. Substantial agreements on quantitative levels between serum and urine were observed for the groups Type B Trichothecenes and Zearalenone. Further research is required to bridge the interpretation of external and internal exposure estimates of the individual on a time scale of hours. Additionally, metabolomic profiling of dietary mycotoxin exposures could help with a comprehensive assessment of single time-point exposures, but also with the identification of chronic exposure biomarkers. Such detailed characterization informs population exposure assessments, and aids in the interpretation of epidemiological health outcomes related to multi-mycotoxin exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)