Provision of low-aflatoxin local complementary porridge flour reduced urinary aflatoxin biomarker in children aged 6-18 months in rural Tanzania.

Aflatoxins are toxic secondary metabolites of fungi that colonize staple food crops, such as maize and groundnut, frequently used in complementary feeding. In preparation for a large trial, this pilot study examined if provision of a low-aflatoxin infant porridge flour made from local maize and groundnuts reduced the prevalence of a urinary aflatoxin biomarker in infants. Thirty-six infants aged 6-18 months were included from four villages in Kongwa District, Tanzania. The study was conducted over 12 days with a three-day baseline period and a 10 days where low-AF porridge flour was provided. Porridge intake of infants was assessed using quantitative 24-h recalls by mothers. Household food ingredients used in infant porridge preparation and urine samples were collected on Days 1-3 (baseline) and 10-12 (follow-up). Aflatoxins were measured in household foods, and AFM1 was measured in urine. At baseline and follow-up, 78% and 97%, respectively, of the infants consumed porridge in the previous 24 h, with a median volume of 220 mL (interquartile range [IQR]: 201, 318) and 460 mL (IQR: 430, 563), respectively (p < 0.001). All 47 samples of homemade flour/ingredients were contaminated with AFs (0.3-723 ng/g). The overall prevalence of individuals with detectable urinary AFM1 was reduced by 81%, from 15/36 (42%) at baseline to 3/36 (8%) at follow-up (p = 0.003). Provision of low-aflatoxin porridge flour was acceptable to caregivers and their infants and successfully reduced the prevalence of detectable urinary AFM1 in infants, thus, confirming its potential to be tested in future large-scale health outcomes trial.

Protocol for the trial to establish a causal linkage between mycotoxin exposure and child stunting: a cluster randomized trial.

BACKGROUND: The number of stunted children has fallen globally but continues to increase in Africa. Stunting is estimated to contribute to 14-17% of child deaths under 5 years of age and is a risk factor for poor cognitive and motor development and educational outcomes. Inadequate dietary intake and disease are thought to be the immediate causes of undernutrition and stunting. However, improving infant diets through complementary feeding interventions has been shown to only modestly reduce stunting. Multiple observational studies demonstrate a dose response relationship between fetal and post-natal aflatoxin exposure and reduced linear growth. METHODS: This community-based cluster randomized trial will measure the effect of a reduced aflatoxin diet on length-for-age Z scores at 18 months in central Tanzania. All 52 health facilities in the Kongwa District of Dodoma Region were randomized into two groups. Starting at 6 months of age, participants in the intervention group receive a low-aflatoxin pre-blended porridge flour containing maize and groundnut (ratio 4:1 respectively) and low-aflatoxin groundnut flour, whereas in the control group the same porridge mix and groundnut flour are promoted through education but acquired by the household. Both groups will receive the same infant and young child feeding education and a thermos flask. A total of 3120 infants between 6 weeks and 3 months of age will be recruited into the study over 1 year. Data will be collected four times - at recruitment and when the infants are 6, 12 and 18 months of age. In a cohort of 600 infants, additional data will be collected at 9 and 15 months of age. The primary outcome is length-for-age at 18 months. Secondary outcomes include the Z scores for weight-for-age, middle upper arm circumference and head circumference, and the blood biomarker aflatoxin-albumin in the full sample, with the urine biomarker aflatoxin M1 analyzed in the cohort only. DISCUSSION: Better understanding the etiology of childhood stunting can lead to more appropriate interventions and policies to further reduce linear growth faltering and meet the Sustainable Development Goals. TRIAL REGISTRATION: NCT03940547, (April 24, 2019).

Screening for enteroviral meningitis in infants and children-Is it useful in clinical practice?

Enteroviral meningitis in infants and children commonly leads to hospital admission. Diagnosing viral meningitis can be difficult clinically. We examined the usefulness of enteroviral polymerase chain reaction (PCR) testing using cerebrospinal fluid (CSF) samples on clinical practice by comparing positive enteroviral CSF PCR cases (n = 39/136) to negative controls using both clinical outcomes and laboratory parameters. A positive result correlated with a reduced admission to high dependency unit, reduced the duration of antibiotics and a shorter length of stay (P < .05). Adjusted CSF white cell count > 5/µL correlated with positive PCR (P < .05) but would have missed 32% of cases of enteroviral meningitis. Following these findings, an algorithm for the management of suspected viral meningitis has been introduced.

Trends in neonicotinoid pesticide residues in food and water in the United States, 1999-2015.

BACKGROUND: Neonicotinoids are a class of systemic insecticides widely used on food crops globally. These pesticides may be found in "off-target" food items and persist in the environment. Despite the potential for extensive human exposure, there are limited studies regarding the prevalence of neonicotinoid residues in foods sold and consumed in the United States. METHODS: Residue data for seven neonicotinoid pesticides collected between 1999 and 2015 by the US Department of Agriculture's Pesticide Data Program (PDP) were collated and summarized by year across various food commodities, including fruit, vegetable, meat, dairy, grain, honey, and baby food, as well as water to qualitatively describe and examine trends in contamination frequency and residue concentrations. RESULTS: The highest detection frequencies (DFs) for neonicotinoids by year on all commodities were generally below 20%. Average DFs over the entire study period, 1999-2015, for domestic and imported commodities were similar at 4.5%. For all the samples (both domestic and imported) imidacloprid was the neonicotinoid with the highest overall detection frequency at 12.0%. However, higher DFs were observed for specific food commodity-neonicotinoid combinations such as: cherries (45.9%), apples (29.5%), pears (24.1%) and strawberries (21.3%) for acetamiprid; and cauliflower (57.5%), celery (20.9%), cherries (26.3%), cilantro (30.6%), grapes (28.9%), collard greens (24.9%), kale (31.4%), lettuce (45.6%), potatoes (31.2%) and spinach (38.7%) for imidacloprid. Neonicotinoids were also detected in organic commodities, (DF < 6%). Individual commodities with at least 5% of samples testing positive for two or more neonicotinoids included apples, celery, and cherries. Generally, neonicotinoid residues on food commodities did not exceed US Environmental Protection Agency tolerance levels. Increases in detection trends for both finished and untreated water samples for imidacloprid were observed from 2004 to 2011. CONCLUSIONS: Analysis of PDP data indicates that low levels of neonicotinoids are present in commonly-consumed fruits and vegetables sold in the US. Trends in detection frequencies suggest an increase in use of acetamiprid, clothianidin and thiamethoxam as replacements for imidacloprid. Given these findings, more extensive surveillance of the food and water supply is warranted, as well as biomonitoring studies and assessment of cumulative daily intake in high risk groups, including pregnant women and infants.

Monitoring Early Life Mycotoxin Exposures via LC-MS/MS Breast Milk Analysis.

Infants are particularly susceptible toward the toxic effects of food contaminants, including mycotoxins. However, multimycotoxin exposure assessment in breast milk has received very limited attention so far, resulting in a poor understanding of coexposures during early life. Here, we present the development and application of a highly sensitive, specific, and quantitative assay assessing up to 28 mycotoxins, including regulated (aflatoxins, ochratoxin A, deoxynivalenol, zearalenone) and emerging mycotoxins as well as key metabolites by LC-MS/MS. After careful optimization of the sample preparation procedure, a QuEChERS protocol combined with a freeze-out step was validated in-house. The limits of quantification varied between 0.009 and 2.9 ng/mL, and for most analytes extraction recovery (74-116%) and intermediate precision (2-20%) were satisfactory. The method was applied to examine multiple breast milk samples obtained from 22 women ( n = 75 in total) from Ogun State, Nigeria. Most samples were either entirely free of mycotoxins or contaminated to a minimal extent with beauvericin (56%), enniatin B (9%), ochratoxin A (15%), and aflatoxin M1 (1%). The most abundant mycotoxin was beauvericin, which was not reported in this biological fluid before, with concentrations up to 0.019 ng/mL. In conclusion, the method demonstrated to be fit for purpose to determine and quantify low background contaminations in human breast milk. On the basis of the high sensitivity of the novel analytical method, it was possible to deduce that tolerable daily intake values were not exceeded by breastfeeding in the examined infants.

Biomonitoring of Mycotoxins in Human Breast Milk: Current State and Future Perspectives.

Human breast milk is considered as the best and ideal form of nutrition for infants. However, food contaminants such as mycotoxins, which may be transferred from maternal blood to milk, are poorly described. Mycotoxins are a major group of natural toxins frequently detected in foods. Here, we review the current state-of-the-art in the monitoring of mycotoxins in human breast milk, i.e., knowledge on occurrence, metabolism, and analytical assays utilized for their quantification. We highlight that most of the data captured to date have not been verified with the precision now capable utilizing LC-MS/MS and LC-HRMS approaches. One concern is that some studies may overestimate individual measures, and most cannot capture the patterns and levels of mycotoxin mixtures. We propose accurate assessment as a priority, especially for aflatoxins, fumonisins, ochratoxin A, zearalenone, and deoxynivalenol as well as their major metabolites. However, also so-called emerging toxins such as citrinin, the enniatins, beauvericin, aurofusarin, or Alternaria toxins should be considered to evaluate their potential relevance. Key requirements for analytical quality assurance are identified and discussed to guide future developments in this area. Moreover, research needs including investigations of lactational transfer rates, the role of human metabolism for bioactivation or detoxification, and an evaluation of potential combinatory effects of different mycotoxins are pointed out. It is hoped that LC-MS based multianalyte methods will enable more accurate, rapid and affordable human biomonitoring approaches that support informed decisions for maternal and infant health.

The Potential Role of Mycotoxins as a Contributor to Stunting in the SHINE Trial.

Children in developing countries experience multiple exposures that are harmful to their growth and development. An emerging concern is frequent exposure to mycotoxins that contaminate a wide range of staple foods, including maize and groundnuts. Three mycotoxins are suspected to contribute to poor child health and development: aflatoxin, fumonisin, and deoxynivalenol. We summarize the evidence that mycotoxin exposure is associated with stunting, and propose that the causal pathway may be through environmental enteric dysfunction (EED) and disturbance of the insulin-like growth factor 1 (IGF-1) axis. The objectives of this substudy are to assess the relationship between agricultural and harvest practices and mycotoxin exposure; to evaluate associations between mycotoxin exposure and child stunting; and to investigate EED as a potential pathway linking mycotoxin exposure to child stunting, to inform potential areas for intervention.

Modulation of porcine ß-defensins 1 and 2 upon individual and combined Fusarium toxin exposure in a swine jejunal epithelial cell line.

Defensins are small antimicrobial peptides (AMPs) that play an important role in the innate immune system of mammals. Since the effect of mycotoxin contamination of food and feed on the secretion of intestinal AMPs is poorly understood, the aim of this study was to elucidate the individual and combined effects of four common Fusarium toxins, deoxynivalenol (DON), nivalenol (NIV), zearalenone (ZEA), and fumonisin B1 (FB1), on the mRNA expression, protein secretion, and corresponding antimicrobial effects of porcine ß-defensins 1 and 2 (pBD-1 and pBD-2) using a porcine jejunal epithelial cell line, IPEC-J2. In general, upregulation of pBD-1 and pBD-2 mRNA expression occurred following exposure to Fusarium toxins, individually and in mixtures (P < 0.05). However, no significant increase in secreted pBD-1 and pBD-2 protein levels was observed, as measured by enzyme-linked immunosorbent assay (ELISA). Supernatants from IPEC-J2 cells exposed to toxins, singly or in combination, however, possessed significantly less antimicrobial activity against Escherichia coli than untreated supernatants. When single toxins and two-toxin combinations were assessed, toxicity effects were shown to be nonadditive (including synergism, potentiation, and antagonism), suggesting interactive toxin effects when cells are exposed to mycotoxin combinations. The results show that Fusarium toxins, individually and in mixtures, activate distinct antimicrobial defense mechanisms possessing the potential to alter the intestinal microbiota through diminished antimicrobial effects. Moreover, by evaluating toxin mixtures, this improved understanding of toxin effects will enable more effective risk assessments for common mycotoxin combinations observed in contaminated food and feed.

Infant and Young Child Feeding Practices and Mycotoxin Contamination of Complementary Food Ingredients in Kongwa District, Tanzania.

Background: Inadequate infant and young child feeding (IYCF) practices in low income countries contribute to poor child growth and development. Objectives: To assess IYCF practices and mycotoxin contamination in complementary food ingredients across 2 seasons in Kongwa District, Tanzania. Methods: Early feeding practices in 115 rural households from 25 villages in Kongwa District, Dodoma region, Tanzania, were assessed. The primary caregiver for the index child (6-18 mo of age) was interviewed using a structured dietary questionnaire at recruitment (October/November 2017), and revisited 6 mo later. The questionnaire included questions on typical food consumption in the past 24 h. This study reports 7 of the revised and new IYCF indicators, including minimum dietary diversity (MDD). Aflatoxins (AF) and fumonisins (FUM) were analyzed in complementary food ingredients for pooled household samples to broadly establish patterns of contamination at the village level. Results: The MDD was not met for 80% of infants at recruitment (survey 1) as compared with 56% in survey 2 (P < 0.05). Changes in MDD between the 2 surveys were dependent on season but not age. Maize was consumed by >90% of households in both surveys, whereas groundnut was consumed by 44% and 64% of households in surveys 1 and 2, respectively. AF concentrations in maize and groundnuts were found to be higher in survey 1 than in survey 2. Overall, AF exceeded the legal limit in 18% of maize and 61% of groundnut pooled samples in both surveys. Maize was also contaminated with significant FUM concentrations. Conclusions: Poor diets were common among children in Kongwa District. Reliance on maize and groundnuts exposes this vulnerable age group to AF (also to FUM in maize). Inadequate diet and exposure to AF and FUM have separately been linked to linear growth retardation. Low diet diversity and mycotoxins contamination are plausible causes for poor growth and development among infants in Central Tanzania. Curr Dev Nutr 20XX;x:xx.

The role of biomarkers in evaluating human health concerns from fungal contaminants in food.

Mycotoxins are toxic secondary metabolites that globally contaminate an estimated 25 % of cereal crops and thus exposure is frequent in many populations. Aflatoxins, fumonisins and deoxynivalenol are amongst those mycotoxins of particular concern from a human health perspective. A number of risks to health are suggested including cancer, growth faltering, immune suppression and neural tube defects; though only the demonstrated role for aflatoxin in the aetiology of liver cancer is widely recognised. The heterogeneous distribution of mycotoxins in food restricts the usefulness of food sampling and intake estimates; instead biomarkers provide better tools for informing epidemiological investigations. Validated exposure biomarkers for aflatoxin (urinary aflatoxin M(1), aflatoxin-N7-guaunine, serum aflatoxin-albumin) were established almost 20 years ago and were critical in confirming aflatoxins as potent liver carcinogens. Validation has included demonstration of assay robustness, intake v. biomarker level, and stability of stored samples. More recently, aflatoxin exposure biomarkers are revealing concerns of growth faltering and immune suppression; importantly, they are being used to assess the effectiveness of intervention strategies. For fumonisins and deoxynivalenol these steps of development and validation have significantly advanced in recent years. Such biomarkers should better inform epidemiological studies and thus improve our understanding of their potential risk to human health.

Mycotoxin-mixture assessment in mother-infant pairs in Nigeria: From mothers' meal to infants' urine.

Exposure to food and environmental contaminants is a global environmental health issue. In this study, innovative LC-MS/MS approaches were applied to investigate mycotoxin co-exposure in mother-infant pairs (n = 23) by analyzing matched plate-ready food, breast milk and urine samples of mothers and their exclusively breastfed infants. The study revealed frequent co-occurrence of two to five mycotoxins. Regulated (e.g. aflatoxins, deoxynivalenol and ochratoxin A) and emerging mycotoxins (e.g. alternariol monomethyl ether and beauvericin) were frequently detected (3 %-89 % and 45 %-100 %), in at least one specimen. In addition, a moderate association of ochratoxin A in milk to urine of mothers (r = 0.47; p = 0.003) and infants (r = 0.52; p = 0.019) but no other significant correlations were found. Average concentration levels in food mostly did not exceed European maximum residue limits, and intake estimates demonstrated exposure below tolerable daily intake values. Infants were exposed to significantly lower toxin levels compared to their mothers, indicating the protective effect of breastfeeding. However, the transfer into milk and urine and the resulting chronic low-dose exposure warrant further monitoring. In the future, occurrence of mycotoxin-mixtures, and their combined toxicological effects need to be comprehensively considered and implemented in risk management strategies. These should aim to minimize early-life exposure in critical developmental stages.

Mycotoxin exposure biomonitoring in breastfed and non-exclusively breastfed Nigerian children.

A multi-specimen, multi-mycotoxin approach involving ultra-sensitive LC-MS/MS analysis of breast milk, complementary food and urine was applied to examine mycotoxin co-exposure in 65 infants, aged 1-18 months, in Ogun state, Nigeria. Aflatoxin M1 was detected in breast milk (4/22 (18%)), while six other classes of mycotoxins were quantified; including dihydrocitrinone (6/22 (27%); range: 14.0-59.7 ng/L) and sterigmatocystin (1/22 (5%); 1.2 ng/L) detected for the first time. Seven distinct classes of mycotoxins including aflatoxins (9/42 (21%); range: 1.0-16.2 µg/kg) and fumonisins (12/42 (29%); range: 7.9-194 µg/kg) contaminated complementary food. Mycotoxins covering seven distinct classes with diverse structures and modes of action were detected in 64/65 (99%) of the urine samples, demonstrating ubiquitous exposure. Two aflatoxin metabolites (AFM1 and AFQ1) and FB1 were detected in 6/65 (9%), 44/65 (68%) and 17/65 (26%) of urine samples, respectively. Mixtures of mycotoxin classes were common, including 22/22 (100%), 14/42 (33%) and 56/65 (86%) samples having 2-6, 2-4, or 2-6 mycotoxins present, for breast milk, complementary food and urine, respectively. Aflatoxin and/or fumonisin was detected in 4/22 (18%), 12/42 (29%) and 46/65 (71%) for breast milk, complimentary foods and urine, respectively. Furthermore, the detection frequency, median concentrations and occurrence of mixtures were typically greater in urine of non-exclusively breastfed compared to exclusively breastfed infants. The study provides novel insights into mycotoxin co-exposures in early-life. Albeit a small sample set, it highlights transition to higher levels of infant mycotoxin exposure as complementary foods are introduced, providing impetus to mitigate during this critical early-life period and encourage breastfeeding.

Development and Limitations of Exposure Biomarkers to Dietary Contaminants Mycotoxins.

Mycotoxins are toxic secondary fungal metabolites that frequently contaminate cereal crops globally, presenting exposure hazards to humans and livestock in many settings. The heterogeneous distribution of mycotoxins in food restricts the usefulness of food sampling and intake estimates for epidemiological studies, making validated exposure biomarkers better tools for informing epidemiological investigations. While biomarkers of exposure have served important roles for understanding the public health impact of mycotoxins such as aflatoxins (AF), the science of biomarkers must continue advancing to allow for better understanding of mycotoxins' roles in the etiology of disease and the effectiveness of mitigation strategies. This review will discuss mycotoxin biomarker development approaches over several decades for four toxins of significant public health concerns, AFs, fumonisins (FB), deoxynivalenol (DON), and ochratoxin A (OTA). This review will also highlight some knowledge gaps, key needs and potential pitfalls in mycotoxin biomarker interpretation.

Low dose of zearalenone elevated colon cancer cell growth through G protein-coupled estrogenic receptor.

Colon cancer is one of the leading causes of cancer death worldwide. It is widely believed that environmental factors contribute to colon cancer development. Zearalenone (ZEA) is non-steroidal estrogenic mycotoxin that is widely found in the human diet and animal feeds. Most cancer studies of ZEA focused on estrogen sensitive cancers, while few focused on other types, such as colon cancer; despite the gastrointestinal tract being the first barrier exposed to food contaminants. This study investigated the stimulatory effects of ZEA on colon cancer cell lines and their underlying molecular mechanisms. ZEA promoted anchorage independent cell growth and cell cycle progression through promoting G1-to-S phase transition. Proliferative marker, cyclin D1 and Ki67 were found to be upregulated upon ZEA treatment. G protein-coupled estrogenic receptor 1 (GPER) protein expression was promoted upon ZEA treatment suggesting the involvement of GPER. The growth promoting effect mediated through GPER were suppressed by its antagonist G15. ZEA were found to promote the downstream parallel pathway, MAPK signaling pathway and Hippo pathway effector YAP1. Altogether, our observations suggest a novel mechanism by which ZEA could promote cancer growth and provide a new perspective on the carcinogenicity of ZEA.

Racial and Sex Differences between Urinary Phthalates and Metabolic Syndrome among U.S. Adults: NHANES 2005-2014.

Phthalates, plasticizers ubiquitous in household and personal care products, have been associated with metabolic disturbances. Despite the noted racial differences in phthalate exposure and the prevalence of metabolic syndrome (MetS), it remains unclear whether associations between phthalate metabolites and MetS vary by race and sex. A cross-sectional analysis was conducted among 10,017 adults from the National Health and Nutritional Examination Survey (2005-2014). Prevalence odds ratios (POR) and 95% confidence intervals (CIs) were estimated for the association between 11 urinary phthalate metabolites and MetS using weighted sex and race stratified multivariable logistic regression. Higher MCOP levels were significantly associated with increased odds of MetS among women but not men, and only remained significant among White women (POR Q4 vs. Q1 = 1.68, 95% CI: 1.24, 2.29; p-trend = 0.001). Similarly, the inverse association observed with MEHP among women, persisted among White women only (POR Q4 vs. Q1 = 0.53, 95% CI: 0.35, 0.80; p-trend = 0.003). However, ΣDEHP metabolites were associated with increased odds of MetS only among men, and this finding was limited to White men (POR Q4 vs. Q1 = 1.54, 95% CI: 1.01, 2.35; p-trend = 0.06). Among Black men, an inverse association was observed with higher MEP levels (POR Q4 vs. Q1 = 0.43, 95% CI: 0.24, 0.77; p-trend = 0.01). The findings suggest differential associations between phthalate metabolites and MetS by sex and race/ethnicity.

Determination of Urinary Mycotoxin Biomarkers Using a Sensitive Online Solid Phase Extraction-UHPLC-MS/MS Method.

In the course of assessing the human exposure to mycotoxins, biomarker-based approaches have proven to be important tools. Low concentration levels, complex matrix compositions, structurally diverse analytes, and the large size of sample cohorts are the main challenges of analytical procedures. For that reason, an online solid phase extraction-ultra high-performance liquid chromatography-tandem mass spectrometry (online SPE-UHPLC-MS/MS) method was developed, allowing for the sensitive, robust, and rapid analysis of 11 relevant mycotoxins and mycotoxin metabolites in human urine. The included spectrum of analytes comprises aflatoxin M1 (AFM1), altenuene (ALT), alternariol monomethyl ether (AME), alternariol (AOH), citrinin (CIT) and its metabolite dihydrocitrinone (DH-CIT), fumonisin B1 (FB1), ochratoxin A (OTA), and zearalenone (ZEN) as well as α- and ß-zearalenol (α- and ß-ZEL). Reliable quantitation was achieved by means of stable isotope dilution, except for ALT, AME and AOH using matrix calibrations. The evaluation of method performance displayed low limits of detection in the range of pg/mL urine, satisfactory apparent recovery rates as well as high accuracy and precision during intra- and interday repeatability. Within the analysis of Zimbabwean urine samples (n = 50), the applicability of the newly developed method was shown. In addition to FB1 being quantifiable in all analyzed samples, six other mycotoxin biomarkers were detected. Compared to the occurrence rates obtained after analyzing the same sample set using an established dilute and shoot (DaS) approach, a considerably higher number of positive samples was observed when applying the online SPE method. Owing to the increased sensitivity, less need of sample handling, and low time effort, the herein presented online SPE approach provides a valuable contribution to human biomonitoring of mycotoxin exposure.

A comparison of deoxynivalenol intake and urinary deoxynivalenol in UK adults.

The relationship between deoxynivalenol (DON) intake and first morning urinary DON was examined in UK adults to validate the latter as a biomarker of human exposure. DON was assessed in first morning samples collected during a period of normal diet, a wheat-restriction intervention diet, and partial wheat-restriction intervention in which bread was allowed. During the partial intervention duplicate bread portions were collected for DON analysis. During the normal diet, partial intervention and full intervention, urinary DON was detected in 198/210 (geometric mean 10.1 ng DON mg(-1) creatinine, 95% confidence interval (CI) 8.6-11.6 ng mg(-1); range nd-70.7 ng mg(-1)), in 94/98 (5.9 ng mg(-1), 95% CI 4.8-7.0 ng mg(-1); range nd-28.4 ng mg(-1)), and 17/40 (0.5 ng mg(-1), 95% CI 0.3-0.7 ng mg(-1); range nd-3.3 ng mg(-1)) volunteers, respectively. A strong correlation between DON intake and the urinary biomarker was observed (p <0.001, adjusted r(2) = 0.83) in models adjusting for age, sex and body mass index. These data demonstrate a quantitative correlation between DON exposure and urinary DON, and serve to validate the use of urinary DON as an exposure biomarker.

A comparison of 24 h urinary deoxynivalenol with recent v. average cereal consumption for UK adults.

Deoxynivalenol (DON) is a toxic fungal metabolite found on wheat, maize and barley. We previously reported a significant association between the amount of DON in a single 24 h urine sample and the average cereal intake over 7 d for 300 UK adults. In this more detailed analysis of the data, food diary information (n 255) for the day of urine collection (model I), the previous 24 h period (model II) and the day of urine collection plus the previous 24 h combined (model III) were further examined to assess whether the recent intake of cereal correlated more strongly with urinary DON, compared with the longer-term assessment of usual cereal intake from 7 d food diaries (model IV). DON was detected in 254/255 (99.6 %) urine samples (mean 12.0 microg/d; range not detected-66 microg/d). For all the models, total cereal intake was positively associated with urinary DON (P < 0.001) in each model. The goodness of fit (adjusted R2 value) was used to assess how well each model explained the variation in urinary DON. Model I provided a better goodness of fit (adjusted R2 0.22) than model IV (adjusted R2 0.19), whereas model III provided the best fit (adjusted R2 0.27). These data suggest that the inter-individual variation in urinary DON was somewhat better explained by recent cereal intake compared with usual cereal intake assessed over 7 d.

Mycotoxins in uncooked and plate-ready household food from rural northern Nigeria.

In order to understand the changes in toxic metabolite profiles in uncooked and cooked foods, samples of flour/grain (n = 40) and their corresponding plate-ready food (n = 39) were collected from 40 households in two states of northern Nigeria. The food samples were analyzed for multiple fungal metabolites by LC-MS/MS and daily intakes of mycotoxins in the diets were estimated and compared to established margin of exposure (MOE) and tolerable daily intake (TDI) values. Both food groups contained 65 fungal and plant metabolites, inclusive of 23 mycotoxins. The mean concentrations of aflatoxin B1, beauvericin, fumonisin B1 (FB1), FB2, FB3, hydrolysed FB1, moniliformin and nivalenol were significantly (p < 0.05) higher in flour than in the plate-ready food samples. The levels of several mycotoxins were higher in the flour samples than in plate-ready meals by 129-383%. The dilution effect from proportionate mixing of flour samples with water led to 48-100% reduction in detectable mycotoxins in flour to plate-ready meals. Aflatoxins and fumonisins co-occurred in 36% of the plate-ready foods. Exposures of households to aflatoxins and fumonisins based on 95% CI concentration of mycotoxins in the meals were high, suggesting potential health risks based on calculated low MOE and exceedence of stipulated TDI value, respectively.

Schisandrin A protects intestinal epithelial cells from deoxynivalenol-induced cytotoxicity, oxidative damage and inflammation.

Extensive research has revealed the association of continued oxidative stress with chronic inflammation, which could subsequently affect many different chronic diseases. The mycotoxin deoxynivalenol (DON) frequently contaminates cereals crops worldwide, and are a public health concern since DON ingestion may result in persistent intestinal inflammation. There has also been considerable attention over the potential of DON to provoke oxidative stress. In this study, the cytoprotective effect of Schisandrin A (Sch A), one of the most abundant active dibenzocyclooctadiene lignans in the fruit of Schisandra chinensis (Turcz.) Baill (also known as Chinese magnolia-vine), was investigated in HT-29 cells against DON-induced cytotoxicity, oxidative stress and inflammation. Sch A appeared to protect against DON-induced cytotoxicity in HT-29 cells, and significantly lessened the DON-stimulated intracellular reactive oxygen species and nitrogen oxidative species production. Furthermore, Sch A lowered DON-induced catalase, superoxide dismutase and glutathione peroxidase antioxidant enzyme activities but maintains glutathione S transferase activity and glutathione levels. Mechanistic studies suggest that Sch A reduced DON-induced oxidative stress by down-regulating heme oxygenase-1 expression via nuclear factor (erythroid-derived 2)-like 2 signalling pathway. In addition, Sch A decreased the DON-induced cyclooxygenase-2 expression and prostaglandin E2 production and pro-inflammatory cytokine interleukin 8 expression and secretion. This may be mediated by preventing DON-induced translocation of nuclear factor-κB, as well as activation of mitogen-activated protein kinases pathways. In the light of these findings, we concluded that Sch A exerted a cytoprotective role in DON-induced toxicity in vitro, and it would be valuable to examine in vivo effects.