scholarly journals Burden of disease attributable to exposure to aflatoxins in Portugal using Human biomonitoring data

2019 ◽  
Vol 29 (Supplement_4) ◽  
Author(s):  
C Martins ◽  
A Vidal ◽  
M De Boevre ◽  
S De Saeger ◽  
C Nunes ◽  
...  
Keyword(s):  
Human Biomonitoring ◽  
Health Impact ◽  
Daily Basis ◽  
Urine Samples ◽  
Toxic Effects ◽  
Internal Exposure ◽  
Accurate Estimation ◽  
Food Contaminants ◽  
Portuguese Population ◽  
Individual Level

Abstract Human biomonitoring (HBM) is recognized as an important tool to assess the Human exposure to chemicals, contributing to describe trends and patterns of exposure over time and to identify population groups that could be under risk. Natural chemicals as mycotoxins, fungi metabolites that produce toxic effects in humans, are important compounds that could be found in foods usually consumed worldwide in a daily basis. Mycotoxins as aflatoxins (AFTs) are genotoxic, carcinogenic and immunosuppressive compounds. Hepatocellular carcinoma (HCC) is one of their main health toxic effects and is the third leading cause of cancer deaths worldwide. In Portugal, scarce data are available regarding exposure to AFTs and none previous study used HBM data to characterize comprehensively the burden associated to this exposure. In the scope of the National Food, Nutrition, and Physical Activity Survey of the Portuguese General Population (2015-2016), 24h-urine samples from 94 participants were analyzed by liquid chromatography-mass spectrometry (LC-MS/MS) for the simultaneous determination of AFTs (B1, B2, G1, G2, M1). A model was developed to estimate the health impact of the exposure of Portuguese population to aflatoxins, estimating the number of cases of HCC and DALYs attributed to AFTs exposure. AFTs were detected in 12.8% (AFB1), 16.0% (AFB2) and 19.1% (AFM1) of the 24h-urine samples. The estimated number of extra cases of HCC attributed to this exposure ranged from 17 to 65 cases/year; the associated DALYs for the Portuguese population ranged from 284 to 1802 years. The present study generated, for the first time and within a HBM study, reliable data regarding the exposure of the Portuguese population to AFTs. These data were crucial to characterize the health impact associated to AFTs exposure and to support risk managers to establish preventive policy measures that contribute to ensure the public health protection. Key messages Portuguese population is exposed to aflatoxins, chemical food contaminants that may be harmful (carcinogenic, immunotoxic, mutagenic, teratogenic, hepatotoxic) to humans. Human biomonitoring studies provide realistic data on internal exposure at individual level, contributing to a more accurate estimation of the burden derived from this exposure.

scholarly journals Risk assessment of Portuguese population to multiple mycotoxins: the human biomonitoring approach

2019 ◽  
Vol 29 (Supplement_4) ◽  
Author(s):  
C Martins ◽  
A Vidal ◽  
S De Saeger ◽  
C Nunes ◽  
D Torres ◽  
...  
Keyword(s):  
Hazard Quotient ◽  
Daily Intake ◽  
Human Biomonitoring ◽  
Urine Samples ◽  
Internal Exposure ◽  
Risk Characterization ◽  
Food Contaminants ◽  
Portuguese Population ◽  
Individual Level ◽  
Paired Samples

Abstract 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. 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 analyzed 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. The present study contributed with reliable and evidence-based results, and confirmed that mycotoxins represent a burden and are part of the human exposome of the Portuguese population. Further studies are needed to shed a light on the determinants of exposure in order to contribute for the promotion of public health measures to reduce the mycotoxins’ exposure in Portugal. Key messages Portuguese population is exposed to mycotoxins, chemical food contaminants that may be harmful (carcinogenic, immunotoxic, mutagenic, teratogenic, hepatotoxic) for human health. Human biomonitoring studies provide realistic data on internal exposure at individual level, allowing a more accurate knowledge of the determinants of exposure to these contaminants.

scholarly journals High-Throughput Determination of Major Mycotoxins with Human Health Concerns in Urine by LC-Q TOF MS and Its Application to an Exposure Study

Toxins ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 42
Author(s):  
Noelia Pallarés ◽  
Dionisia Carballo ◽  
Emilia Ferrer ◽  
Yelko Rodríguez-Carrasco ◽  
Houda Berrada
Keyword(s):  
Risk Assessment ◽  
Human Urine ◽  
Solid Phase ◽  
Human Biomonitoring ◽  
Urine Samples ◽  
Food Contaminants ◽  
Potential Health ◽  
Human Urine Samples ◽  
Wide Range

Human biomonitoring constitutes a suitable tool to assess exposure to toxins overcoming the disadvantages of traditional methods. Urine constitutes an accessible biological matrix in biomonitoring studies. Mycotoxins are secondary metabolites produced naturally by filamentous fungi that produce a wide range of adverse health effects. Thus, the determination of urinary mycotoxin levels is a useful tool for assessing the individual exposure to these food contaminants. In this study, a suitable methodology has been developed to evaluate the presence of aflatoxin B2 (AFB2), aflatoxin (AFG2), ochratoxin A (OTA), ochratoxin B (OTB), zearalenone (ZEA), and α-zearalenol (α-ZOL) in urine samples as exposure biomarkers. For this purpose, different extraction procedures, namely, the Solid Phase Extraction (SPE); Dispersive Liquid–Liquid Microextraction (DLLME); and Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) methods were assessed, followed by Liquid Chromatography coupled to Quadrupole Time of Flight Mass Spectrometry with Electrospray Ionization (LC-ESI-QTOF-MS) determination. Then, the proposed methodology was applied to determine mycotoxin concentrations in 56 human urine samples from volunteers and to estimate the potential risk of exposure. The results obtained revealed that 55% of human urine samples analyzed resulted positive for at least one mycotoxin. Among all studied mycotoxins, only AFB2, AFG2, and OTB were detected with incidences of 32, 41, and 9%, respectively, and levels in the range from <LOQ to 69.42 µg/L. Risk assessment revealed a potential health risk, obtaining MoE values < 10,000. However, it should be highlighted that few samples were contaminated, and that more data about mycotoxin excretion rates and their BMDL10 values are needed for a more accurate risk assessment.

Accuracy of equations for predicting 24-h urinary potassium excretion from spot urine samples in Chinese children

2021 ◽  
pp. 1-9
Author(s):  
Xiaolu Nie ◽  
Yaguang Peng ◽  
Siyu Cai ◽  
Zehao Wu ◽  
Ying Zhang ◽  
...  
Keyword(s):  
Urine Samples ◽  
Misclassification Rate ◽  
Accurate Estimation ◽  
Potassium Excretion ◽  
Spot Urine ◽  
Individual Level ◽  
Potassium Intake ◽  
Urinary Potassium ◽  
The Mean ◽  
The Individual

Abstract Accurate assessments of potassium intake in children are important for the early prevention of CVD. Currently, there is no simple approach for accurate estimation of potassium intake in children. We aim to evaluate the accuracy of 24-h urinary potassium excretion (24UKV) estimation in children using three common equations: the Kawasaki, Tanaka and Mage formulas, in a hospital-based setting. A total of 151 participants aged 5–18 years were initially enrolled, and spot urine samples were collected in the whole 24-h duration to measure the concentrations of potassium and creatinine. We calculated the mean difference, absolute and relative difference and misclassification rate between measured 24UKV and the predicted ones using Kawasaki, Tanaka and Mage formulas in 129 participants. The mean measured 24UKV was 1193·3 mg/d in our study. Mean differences between estimated and measured 24UKV were 1215·6, −14·9 and 230·3 mg/d by the Kawasaki, Tanaka and Mage formulas, respectively. All estimated 24UKV were significantly different from the measured values in all the time point (all P < 0·05), except for the predicted values from Tanaka formula using morning, afternoon and evening spot urine. The proportions with relative differences over 40 % were 87·2%, 32·5% and 47·3 % for Kawasaki, Tanaka and Mage formulas, respectively. Misclassification rates were 91·5 % for Kawasaki, 44·4 % for Tanaka and 58·9 % for Mage formula at the individual level. Our findings showed that misclassification could occur on the individual level when using Kawasaki, Tanaka and Mage formulas to estimate 24UKV from spot urine in the child population.

Quantitative risk-benefit assessment of Portuguese fish and other seafood species consumption scenarios

2021 ◽  
pp. 1-32
Author(s):  
Catarina Carvalho ◽  
Daniela Correia ◽  
Milton Severo ◽  
Cláudia Afonso ◽  
Narcisa M. Bandarra ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Health Impact ◽  
Daily Basis ◽  
Benefit Assessment ◽  
Seafood Consumption ◽  
Portuguese Population ◽  
Life Years ◽  
Risk Benefit Assessment ◽  
Alternative Scenarios ◽  
Predatory Fishes

Abstract Portugal has high fish/seafood consumption, which may have both risks and benefits. This study aims to quantify the net health impact of hypothetical scenarios of fish/seafood consumption in the Portuguese population using a risk-benefit assessment methodology. Consumption data from the National Food, Nutrition and Physical Activity Survey 2015-2016 (n=5811) was used to estimate the mean exposure to methylmercury and EPA+DHA in the current and the alternative scenarios considered. Alternative scenarios (alt) were modelled using probabilistic approaches to reflect substitutions from the current consumption in the type of fish/seafood (alt1: excluding predatory fishes; alt2: including only methylmercury low-level fishes) or in the frequency of weekly fish/seafood consumption (alt3 to alt6: 1,3,5 or 7 times a week, replacing fish/seafood meals with meat or others). The overall health impact of these scenarios was quantified using Disability-Adjusted Life Years (DALYs). In the Portuguese population, about 11450 DALYs could be prevented each year if the fish/seafood consumption increased to a daily basis. However, such a scenario would result in 1398 extra DALYs considering the consumption by pregnant women and the respective risk on foetal neurodevelopment. Our findings support a recommendation to increase fish/seafood consumption up to 7 times/week. However, for pregnant women and children, special considerations must be proposed to avoid potential risks on foetal neurodevelopment due to methylmercury exposure.

scholarly journals Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A

2012 ◽  
Vol 17 (2) ◽  
pp. 407-434 ◽  
Author(s):  
Laura N. Vandenberg ◽  
Ibrahim Chahoud ◽  
Jerrold J Heindel ◽  
Vasantha Padmanabhan ◽  
Francisco J.R Paumgartten ◽  
...  
Keyword(s):  
Risk Assessment ◽  
General Population ◽  
Bisphenol A ◽  
Health Effects ◽  
Human Exposure ◽  
Human Biomonitoring ◽  
Urine Samples ◽  
Internal Exposure ◽  
Human Tissues ◽  
Adverse Health Effects

Bisphenol A (BPA) is one of the highest-volume chemicals produced worldwide, and human exposure to BPA is thought to be ubiquitous. Thus, there are concerns that the amount of BPA to which humans are exposed may cause adverse health effects. We examined many possibilities for why biomonitoring and toxicokinetic studies could come to seemingly conflicting conclusions. More than 80 published human biomonitoring studies that measured BPA concentrations in human tissues, urine, blood, and other fluids, along with two toxicokinetic studies of human BPA metabolism were examined. Unconjugated BPA was routinely detected in blood (in the nanograms per milliliter range), and conjugated BPA was routinely detected in the vast majority of urine samples (also in the nanograms per milliliter range). In stark contrast, toxicokinetic studies proposed that humans are not internally exposed to BPA. Available data from biomonitoring studies clearly indicate that the general population is exposed to BPA and is at risk from internal exposure to unconjugated BPA. The two toxicokinetic studies that suggested human BPA exposure is negligible have significant deficiencies, are directly contradicted by hypothesis-driven studies, and are therefore not reliable for risk assessment purposes.

scholarly journals How well do neurosurgeons predict survival in patients with high-grade glioma?

2021 ◽  
Author(s):  
Lisa Millgård Sagberg ◽  
Asgeir S. Jakola ◽  
Ingerid Reinertsen ◽  
Ole Solheim
Keyword(s):  
Median Survival ◽  
Survival Curve ◽  
Binary Logistic Regression ◽  
High Grade Glioma ◽  
Accurate Estimation ◽  
Binary Logistic Regression Analysis ◽  
High Grade ◽  
Clinical Prediction ◽  
Individual Level ◽  
Actual Survival

AbstractDue to the lack of reliable prognostic tools, prognostication and surgical decisions largely rely on the neurosurgeons’ clinical prediction skills. The aim of this study was to assess the accuracy of neurosurgeons’ prediction of survival in patients with high-grade glioma and explore factors possibly associated with accurate predictions. In a prospective single-center study, 199 patients who underwent surgery for high-grade glioma were included. After surgery, the operating surgeon predicted the patient’s survival using an ordinal prediction scale. A survival curve was used to visualize actual survival in groups based on this scale, and the accuracy of clinical prediction was assessed by comparing predicted and actual survival. To investigate factors possibly associated with accurate estimation, a binary logistic regression analysis was performed. The surgeons were able to differentiate between patients with different lengths of survival, and median survival fell within the predicted range in all groups with predicted survival < 24 months. In the group with predicted survival > 24 months, median survival was shorter than predicted. The overall accuracy of surgeons’ survival estimates was 41%, and over- and underestimations were done in 34% and 26%, respectively. Consultants were 3.4 times more likely to accurately predict survival compared to residents (p = 0.006). Our findings demonstrate that although especially experienced neurosurgeons have rather good predictive abilities when estimating survival in patients with high-grade glioma on the group level, they often miss on the individual level. Future prognostic tools should aim to beat the presented clinical prediction skills.

scholarly journals Dried urine spots as sampling technique for multi-mycotoxin analysis in human urine

2021 ◽  
Author(s):  
Jessica Schmidt ◽  
Viktoria Lindemann ◽  
Monica Olsen ◽  
Benedikt Cramer ◽  
Hans-Ulrich Humpf
Keyword(s):  
Ochratoxin A ◽  
Human Urine ◽  
Sampling Strategy ◽  
Sampling Technique ◽  
Human Biomonitoring ◽  
Urine Samples ◽  
Isotope Dilution Analysis ◽  
Tenuazonic Acid ◽  
Stable Isotope Dilution Analysis ◽  
Mycotoxin Analysis

AbstractA simple and effective approach for HPLC-MS/MS based multi-mycotoxin analysis in human urine samples was developed by application of dried urine spots (DUS) as alternative on-site sampling strategy. The newly developed method enables the detection and quantitation of 14 relevant mycotoxins and mycotoxin metabolites, including citrinin (CIT), dihydrocitrinone (DH-CIT), deoxynivalenol (DON), fumonisin B1 (FB1), T-2 Toxin (T-2), HT-2 Toxin (HT-2), ochratoxin A (OTA), 2′R-ochratoxin A (2′R-OTA), ochratoxin α (OTα), tenuazonic acid and allo-tenuazonic acid (TeA + allo-TeA), zearalenone (ZEN), zearalanone (ZAN), α-zearalenol (α-ZEL), and β-zearalenol (β-ZEL). Besides the spotting procedure, sample preparation includes enzymatic cleavage of glucuronic acid conjugates and stable isotope dilution analysis. Method validation revealed low limits of detection in the range of pg/mL urine and excellent apparent recovery rates for most analytes. Stability investigation of DUS displayed no or only slight decrease of the analyte concentration over a period of 28 days at room temperature. The new method was applied to the analysis of a set of urine samples (n = 91) from a Swedish cohort. The four analytes, DH-CIT, DON, OTA, and TeA + allo-TeA, could be detected and quantified in amounts ranging from 0.06 to 0.97 ng/mL, 3.03 to 136 ng/mL, 0.013 to 0.434 ng/mL and from 0.36 to 47 ng/mL in 38.5%, 70.3%, 68.1%, and 94.5% of the samples, respectively. Additional analysis of these urine samples with an established dilute and shoot (DaS) approach displayed a high consistency of the results obtained with both methods. However, due to higher sensitivity, a larger number of positive samples were observed using the DUS method consequently providing a suitable approach for human biomonitoring of mycotoxin exposure.

scholarly journals Acetaminophen Metabolism Revisited Using Non-Targeted Analyses: Implications for Human Biomonitoring

2020 ◽  
Author(s):  
Arthur David ◽  
Jade Chaker ◽  
Thibaut Léger ◽  
Raghad Al-Salhi ◽  
Marlene Danner Dalgaard ◽  
...  
Keyword(s):  
Phase Ii ◽  
Enterohepatic Circulation ◽  
High Resolution Mass Spectrometry ◽  
Parent Compound ◽  
Human Biomonitoring ◽  
Relevant Information ◽  
Point Of View ◽  
Internal Exposure ◽  
Current Standard ◽  
Excretion Rates

The analgesic paracetamol (N-acetyl-4-aminophenol, APAP) is commonly used to relieve pain, fever and malaise. While sales have increased worldwide, a growing body of experimental and epidemiological evidence has suggested APAP as a possible risk factor for various health disorders. To perform internal exposure-based risk assessment, the use of accurate and optimized biomonitoring methods is criticical. However, retrospectively assessing pharmaceutical use of APAP in humans is challenging because of its short half-life. The objective of this study was to address the key biomonitoring issues with APAP using current standard analytical methods based on urinary analyses of free APAP and its phase II conjugates. Using non-targeted analyses based on high-resolution mass spectrometry, we identified in a controlled longitudinal exposure study with male volunteers, unrecognized APAP metabolites with delayed formation and excretion rates. We postulate that these metabolites are formed via the thiomethyl shunt after the enterohepatic circulation as already observed in rodents. Importantly, the conjugated thiomethyl metabolites were (i) of comparable diagnostic sensitivity as the free APAP and its phase II conjugates detected by current methods; (ii) had delayed peak levels in blood and urine compared to other APAP metabolites and therefore potentially extend the window of exposure assessment; and (iii) provide relevant information regarding metabolic pathways of interest from a toxicological point of view. Including these metabolites in future APAP biomonitoring methods provide an option to decrease potential underestimation of APAP use and challenges the notion that the standard methods in biomonitoring based exclusively on the parent compound and its phase II metabolites are adequate for human biomonitoring of non-persistant chemical such as APAP. <br>

scholarly journals Development of a Sensitive and Reliable UHPLC-MS/MS Method for the Determination of Multiple Urinary Biomarkers of Mycotoxin Exposure

Toxins ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 193 ◽  
Author(s):  
Zhezhe Liu ◽  
Xiaoxue Zhao ◽  
Libiao Wu ◽  
Shuang Zhou ◽  
Zhiyong Gong ◽  
...  
Keyword(s):  
Human Urine ◽  
Solid Phase ◽  
Accurate Determination ◽  
Fumonisin B1 ◽  
High Sensitivity ◽  
Human Biomonitoring ◽  
Urine Samples ◽  
Specific Method ◽  
Alternariol Monomethyl Ether

A variety of mycotoxins from different sources frequently contaminate farm products, presenting a potential toxicological concern for animals and human. Mycotoxin exposure has been the focus of attention for governments around the world. To date, biomarkers are used to monitor mycotoxin exposure and promote new understanding of their role in chronic diseases. The goal of this research was to develop and validate a sensitive UHPLC-MS/MS method using isotopically-labeled internal standards suitable for accurate determination of 18 mycotoxin biomarkers, including fumonisins, ochratoxins, Alternaria and emerging Fusarium mycotoxins (fumonisin B1, B2, and B3, hydrolyzed fumonisin B1 and B2, ochratoxin A, B, and alpha, alternariol, alternariol monomethyl ether, altenuene, tentoxin, tenuazonic acid, beauvericin, enniatin A, A1, B, and B1) in human urine. After enzymatic digestion with β-glucuronidase, human urine samples were cleaned up using HLB solid phase extraction cartridges prior to instrument analysis. The multi-mycotoxin and analyte-specific method was validated in-house, providing satisfactory results. The method provided good linearity in the tested concentration range (from LOQ up to 25–500 ng/mL for different analytes), with R2 from 0.997 to 0.999. The limits of quantitation varied from 0.0002 to 0.5 ng/mL for all analytes in urine. The recoveries for spiked samples were between 74.0% and 133%, with intra-day precision of 0.5%–8.7% and inter-day precision of 2.4%–13.4%. This method was applied to 60 urine samples collected from healthy volunteers in Beijing, and 10 biomarkers were found. At least one biomarker was found in all but one of the samples. The high sensitivity and accuracy of this method make it practical for human biomonitoring and mycotoxin exposure assessment.

scholarly journals Estimating 24-Hour Sodium Excretion from Spot Urine Samples in Chinese Adults: Can Spot Urine Substitute 24-Hour Urine Samples?

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 798
Author(s):  
Jianwei Xu ◽  
Jiyu Zhang ◽  
Min Liu ◽  
Yamin Bai ◽  
Xiaolei Guo ◽  
...  
Keyword(s):  
Sodium Excretion ◽  
Population Level ◽  
Relative Difference ◽  
Urine Samples ◽  
Misclassification Rate ◽  
Absolute Difference ◽  
Sample Collection ◽  
Spot Urine ◽  
Individual Level ◽  
Chinese Populations

Several estimating equations for predicting 24-h urinary sodium (24-hUNa) excretion using spot urine (SU) samples have been developed, but have not been readily available to Chinese populations. We aimed to compare and validate the six existing methods at population level and individual level. We extracted 1671 adults eligible for both 24-h urine and SU sample collection. Mean biases (95% CI) of predicting 24-hUNa excretion using six formulas were 58.6 (54.7, 62.5) mmol for Kawasaki, −2.7 (−6.2, 0.9) mmol for Tanaka, −24.5 (−28.0, −21.0) mmol for the International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT) with potassium, –26.8 (−30.1, −23.3) mmol for INTERSALT without potassium, 5.9 (2.3, 9.6) mmol for Toft, and −24.2 (−27.7, −20.6) mmol for Whitton. The proportions of relative difference >40% with the six methods were nearly a third, and the proportions of absolute difference >51.3 mmol/24-h (3 g/day salt) were more than 40%. The misclassification rate were all >55% for the six methods at the individual level. Although the Tanaka method could offer a plausible estimation for surveillance of the population sodium excretion in Shandong province, caution remains when using the Tanaka formula for other provincial populations in China. However, these predictive methods were inadequate to evaluate individual sodium excretion.

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