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Soybean is a critical food and nutritional security crop in Rwanda. Promoted by the Rwandan National Agricultural Research System for both adults and as an infant weaning food, soybean is grown by approximately 40% of households. Soybean may be susceptible to the growth of mycotoxin-producing moulds; however, data has been contradictory. Mycotoxin contamination is a food and feed safety issue for grains and other field crops. This study aimed to determine the extent of mycotoxin contamination in soybean, and to assess people's awareness on mycotoxins. A farm-level survey was conducted in 2015 within three agro-ecological zones of Rwanda suitable for soybean production. Soybean samples were collected from farmers (n=300) who also completed questionnaires about pre-and post-harvest farm practices, and aflatoxin awareness. The concentration of total aflatoxin in individual soybean samples was tested by enzyme-linked immunosorbent assay (ELISA) using a commercially-available kit. Other mycotoxins were analyzed using liquid chromatography-mass spectrometry (LC-MS/MS) on 10 selected sub samples. Only 7.3% of the respondents were aware of aflatoxin contamination in foods, but farmers observed good postharvest practices including harvesting the crop when the pods were dry. Using enzyme-linked immunosorbent assay (ELISA), only one sample had a concentration (11 [micro]g/kg) above the most stringent EU maximum permitted limit of 4 [micro]g/kg. Multi-mycotoxins liquid chromatography-mass spectrometry (LC-MS/MS) results confirmed that soybeans had low or undetectable contamination; only one sample contained 13 [micro]g/kg of sterigmatocystine. The soybean samples from Rwanda obtained acceptably low mycotoxin levels. Taken together with other studies that showed that soybean is less contaminated by mycotoxins, these results demonstrate that soybean can be promoted as a nutritious and safe food. However, there is a general need for educating farmers on mycotoxin contamination in food and feed to ensure better standards are adhered to safeguard the health of the consumers regarding these fungal secondary metabolites.Key words: soybean, safety, mould, aflatoxin, mycotoxins, sterigmatocystine, ELISA, LC-MS/MS, Rwanda, INTRODUCTIONSoybeans (Glycine max L.) are legumes originating from China before 2500BC that were utilized as source of food. The western world discovered soybeans in the 19th century as a source [...]

Mycotoxins constitute a relevant group of food contaminants with several associated health outcomes such as estrogenic, immunotoxic, nephrotoxic and teratogenic effects. Although scarce data are available in Portugal, human biomonitoring studies have been globally developed to assess the exposure to mycotoxins at individual level. In order to overcome this lack of data, the present study concerned the analysis of mycotoxins in 24h urine and first-morning urine paired samples from 94 participants enrolled within the scope of the National Food, Nutrition, and Physical Activity Survey of the Portuguese General Population (2015-2016). Following a salt-assisted matrix extraction, urine samples were analysed by liquid chromatography-mass spectrometry for the simultaneous determination of 37 urinary mycotoxins' biomarkers and data obtained used to estimate the probable daily intake as well as the risk characterization applying the Hazard Quotient approach. Results revealed the exposure of Portuguese population to zearalenone, deoxynivalenol, ochratoxin A, alternariol, citrinin and fumonisin B1 through the quantification in 24h urine and first-morning urine paired samples. Risk characterization data revealed a potential concern to some reported mycotoxins since the reference intake values were exceeded by some of the considered participants. Alternariol was identified for the first time in urine samples from a European country; however, risk characterization was not performed due to lack of reference intake value. These results confirmed mycotoxins as part of the human exposome of the Portuguese population reinforcing the need for further studies regarding the determinants of exposure. [ABSTRACT FROM AUTHOR]

To date, the changes in maternal metabolic response associated with prenatal aflatoxin exposure remain largely unknown. This study investigated the effects of prenatal aflatoxin exposure on the maternal serum metabolome in rural Ethiopia. A total of 309 pregnant women were enrolled prospectively, and their serum aflatoxin concentrations were measured using targeted liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Serum metabolic fingerprints were obtained using laser-assisted rapid evaporative ionization mass spectrometry (LA-REIMS), followed by combination of univariate and multivariate statistical modelling to evaluate changes in circulating metabolic features between aflatoxin-exposed and unexposed mothers and to select discriminatory metabolic features. The analysis revealed that 81.8% of women were exposed to aflatoxins, with a median concentration of 12.9 pg/mg albumin. The orthogonal partial least square discriminant analysis (OPLS-DA) regression model demonstrated significant disparities in the serum metabolome when comparing Ethiopian pregnant women with low vs high aflatoxin exposure. Thirty-two differentially expressed metabolic features were identified, affecting aminoacyl-tRNA biosynthesis pathway. Several discriminatory metabolites have been identified, including glutamine, tryptophan, tyrosine, carnosine, and 1-methylnicotinamide. In conclusion, our findings indicate that aflatoxin exposure during pregnancy have shown disparities in the maternal serum metabolome, primarily affecting protein synthesis. Further research is needed to identify specific metabolite biomarkers and elucidate the underlying mechanisms., (© 2024. The Author(s).)

Background: Mycotoxins, fungal metabolites prevalent in many foods, are recognized for their role in carcinogenesis, especially when interacting with oncogenic viruses., Objectives: This scoping review synthesizes current evidence on the human cancer risk associated with mycotoxin exposure and oncogenic virus infections., Methods: Searches were conducted on PubMed, Embase, and Web of Science. Studies were selected based on the PECOS framework. Data extraction involved narrative and qualitative presentation of findings, with meta-analysis where feasible. Risk of bias and outcome quality were assessed using the OHAT tool and GRADE approach., Results: From 25 included studies, 18 focused on aflatoxins and hepatitis viruses in hepatocellular carcinoma (HCC). Four studies examined aflatoxin B1 (AFB1) and human papilloma virus (HPV) in cervical cancer, while three investigated AFB1 with Epstein-Barr virus (EBV) in lymphomagenesis. The review highlights a significant synergistic effect between AFB1 and hepatitis B and C viruses in HCC development. Significant interactions between AFB1 and HPV, as well as AFB1 and EBV, were observed, but further research is needed., Conclusions: The synergistic impact of mycotoxins and oncogenic viruses is a critical public health concern. Future research, especially prospective cohort studies and investigations into molecular mechanisms, is essential to address this complex issue.

Background: Mycotoxin exposure during pregnancy has been associated with adverse birth outcomes and poor infant growth. We assessed multiple biomarkers and metabolites of exposure to mycotoxins at birth and their associations with birth outcomes and infant growth in 274 newborns in rural Burkina Faso., Methods: Whole-blood microsamples were analyzed for mycotoxin concentrations in newborns in the Biospecimen substudy nested in the MIcronutriments pour la SAnté de la Mère et de l'Enfant-III trial using ultra-performance liquid chromatography coupled with tandem mass spectrometry. Unadjusted and adjusted associations between mycotoxin exposure, and birth outcomes and infant growth at 6 mo were estimated using linear regression models for continuous outcomes and linear probability models with robust variance estimation for binary outcomes. Infant growth trajectories from birth to 6 mo were compared by exposure status using mixed-effects models with a random intercept for the individual infant and a random slope for the infant's age., Results: Ochratoxin A (OTA) exposure was detected in 38.3% of newborns, with other mycotoxins being detected in the range of 0.36% and 4.01%. OTA exposure was significantly associated with adverse birth outcomes, such as lower birth weight [β (95% CI): -0.11 kg (-0.21, 0.00); P = 0.042] and ponderal index [β (95% CI): -0.62 gm/cm 3 (-1.19, -0.05); P = 0.034], and a marginally significant lower length growth trajectories during the first 6 mo [β (95% CI): -0.08 cm/mo (-0.15, 0.0); P = 0.057]., Conclusions: OTA exposure was prevalent among newborns and also associated with lower growth at birth and during the first 6 mo. The results emphasize the importance of nutrition-sensitive strategies to mitigate dietary OTA, as well as adopting food safety measures in Burkina Faso during the fetal period of development., Competing Interests: Conflicts of interest The authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Esophageal cancer (EC) is a malignancy with a poor prognosis and a five-year survival rate of less than 20%. It is the ninth most frequent cancer globally and the sixth leading cause of cancer-related deaths. The incidence of EC has been found to vary significantly by geography, indicating the importance of environmental and lifestyle factors along with genetic factors in the onset of the disease. In this work, we investigated mycotoxin exposure in a case-control study from the Arsi-Bale districts of Oromia regional state in Ethiopia, where there is a high incidence of EC while alcohol and tobacco use - two established risk factors for EC - are very rare., Methods: Internal exposure to 39 mycotoxins and metabolites was assessed by liquid chromatography-tandem mass spectrometry in plasma samples of EC cases (n = 166) and location-matched healthy controls (n = 166) who shared similar dietary sources. Demographic and lifestyle data were collected using structured questionnaires. Principal Component Analysis and machine learning models were used to identify the most relevant demographic, lifestyle, and mycotoxin (co-)exposure variables associated with EC. Multivariate binary logistic regression analysis was used to assess EC risk., Result: Evidence of mycotoxin exposure was observed in all plasma samples, with 10 different mycotoxins being detected in samples from EC cases, while only 6 different mycotoxins were detected in samples from healthy controls. Ochratoxin A was detected in plasma from all cases and controls, while tenuazonic acid was detected in plasma of 145 (87.3%) cases and 71 (42.8%) controls. Using multivariable logistic regression analysis, exposure to tenuazonic acid (AOR = 1.88 [95% CI: 1.68-2.11]) and to multiple mycotoxins (AOR = 2.54 [95% CI: 2.10-3.07]) were positively associated with EC., Conclusion: All cases and controls were exposed to at least one mycotoxin. Cases were exposed to a statistically significantly higher number of mycotoxins than controls. Exposure to tenuazonic acid and to multiple mycotoxins were associated with increased risk of EC in the study population. Although aflatoxin B1-lysine and the ratio of sphinganine to sphingosine (as a biomarker of effect to fumonisin exposure) were not assessed in this study, our result emphasizes the need to characterize the effect of mycotoxin co-exposure as part of the exposome and include it in risk assessment, since the current mycotoxin safety levels do not consider the additive or synergistic effects of mycotoxin co-exposure. Moreover, a prospective study design with regular sampling should be considered in this high incidence area of EC in Ethiopia to obtain conclusive results on the role of mycotoxin exposure in the onset and development of the disease., Competing Interests: Declaration of competing interest All the authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier GmbH.)

Mycotoxins, natural toxins produced by fungi, contaminate nearly 80% of global food crops. Alternaria mycotoxins, including alternariol (AOH), alternariol monomethylether (AME), and tenuazonic acid (TeA), present a health concern due to their prevalence in various plants and fruits. Exposure to these toxins exceeds the threshold of toxicological concern in some European populations, especially infants and toddlers. Despite this, regulatory standards for Alternaria toxins remain absent. The lack of toxicokinetic parameters, reference levels, and sensitive detection methods complicates risk assessment and highlights the necessity for advanced biomonitoring (HBM) techniques. This study addresses these challenges by developing and validating ultra-high performance liquid chromatography method coupled with tandem mass spectrometry to quantify AOH, AME, TeA, and their conjugates in multiple biological matrices. The validated method demonstrates robust linearity, precision, recovery (94-111%), and sensitivity across urine (LOD < 0.053 ng/mL), capillary blood (LOD < 0.029 ng/mL), and feces (LOD < 0.424 ng/g), with significantly lower LOD for TeA compared to existing methodologies. The application of minimally invasive microsampling techniques for the blood collection enhances the potential for large-scale HBM studies. These advancements represent a step toward comprehensive HBM and exposure risk assessments for Alternaria toxins, facilitating the generation of data for regulatory authorities., Competing Interests: The authors declare no conflicts of interest.

Physiologically based pharmacokinetic (PBPK) models were utilized to investigate potential interactions between aflatoxin B1 (AFB1) and efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor drug and inducer of several CYP enzymes, including CYP3A4. PBPK simulations were conducted in a North European Caucasian and Black South African population, considering different dosing scenarios. The simulations predicted the impact of EFV on AFB1 metabolism via CYP3A4 and CYP1A2. In vitro experiments using human liver microsomes (HLM) were performed to verify the PBPK predictions for both single- and multiple-dose exposures to EFV. Results showed no significant difference in the formation of AFB1 metabolites when combined with EFV (0.15 µM) compared to AFB1 alone. However, exposure to 5 µM of EFV, mimicking chronic exposure, resulted in increased CYP3A4 activity, affecting metabolite formation. While co-incubation with EFV reduced the formation of certain AFB1 metabolites, other outcomes varied and could not be fully attributed to CYP3A4 induction. Overall, this study provides evidence that EFV, and potentially other CYP1A2/CYP3A4 perpetrators, can impact AFB1 metabolism, leading to altered exposure to toxic metabolites. The results emphasize the importance of considering drug interactions when assessing the risks associated with mycotoxin exposure in individuals undergoing HIV therapy in a European and African context.

Epstein-Barr Virus (EBV) infects more than 90% of the adult population worldwide. EBV infection is associated with Burkitt lymphoma (BL) though alone is not sufficient to induce carcinogenesis implying the involvement of co-factors. BL is endemic in African regions faced with mycotoxins exposure. Exposure to mycotoxins and oncogenic viruses has been shown to increase cancer risks partly through the deregulation of the immune response. A recent transcriptome profiling of B cells exposed to aflatoxin B1 (AFB1) revealed an upregulation of the Chemokine ligand 22 (CCL22) expression although the underlying mechanisms were not investigated. Here, we tested whether mycotoxins and EBV exposure may together contribute to endemic BL (eBL) carcinogenesis via immunomodulatory mechanisms involving CCL22. Our results revealed that B cells exposure to AFB1 and EBV synergistically stimulated CCL22 secretion via the activation of Nuclear Factor-kappa B pathway. By expressing EBV latent genes in B cells, we revealed that elevated levels of CCL22 result not only from the expression of the latent membrane protein LMP1 as previously reported but also from the expression of other viral latent genes. Importantly, CCL22 overexpression resulting from AFB1-exposure in vitro increased EBV infection through the activation of phosphoinositide-3-kinase pathway. Moreover, inhibiting CCL22 in vitro and in humanized mice in vivo limited EBV infection and decreased viral genes expression, supporting the notion that CCL22 overexpression plays an important role in B cell infection. These findings unravel new mechanisms that may underpin eBL development and identify novel pathways that can be targeted in drug development., Competing Interests: Competing interests statement:The authors declare no competing interest.