Quantification of chlorinated paraffins by chromatography coupled to high-resolution mass spectrometry - Part A: Influence of gas chromatography and ionisation source parameters.

The analysis of chlorinated paraffins (CPs) has become a major analytical challenge. GC-ECNI-HRMS coupling is often used to analyse and quantify them. However, the influence of certain GC and ECNI parameters on the responses of polychlorinated n-alkanes (PCAs), the dominant components of CPs, has hardly been studied. In this paper, we investigated not only the influence of GC column characteristics, but also oven, GC inlet and source temperatures for simultaneous analysis of PCAs with chain-length ranging from 10 up to 20 carbon atoms (PCAs-C10-20). Particular attention was paid to the absolute response and PCA homologue group pattern obtained for a CP technical mixture. The optimum conditions for a wide homologue group determination were GC inlet, final gradient and ion source temperatures set at 220-240 °C, 340 °C and 200 °C. At the same time, a higher response was obtained with the Optima 5HT column compared to Optima 1 column, and with a length and film thickness of 12.5 m and 0.25 µm, respectively. The homologue group pattern of the technical mixture studied was significantly modified as a function of the source and GC inlet temperatures, film thickness and composition of the stationary phase. Here we recommend conditions that will improve the overall PCA pattern, in order to better characterise their occurrence in future environmental monitoring and exposure assessment.

Deeper insights into the effects of low dietary levels of polychlorinated biphenyls on pig metabolism using gas chromatography-high resolution mass spectrometry metabolomics.

Polychlorinated biphenyls (PCBs) are a class of contaminants of great concern, linked to the development of many chronic diseases. Adverse effects of PCBs have been documented in humans after accidental and massive exposure. However, little is known about the effect of chronic exposure to low-dose PCB mixtures, and studies regarding scattered lifetime exposures to non-dioxin-like (NDL)-PCBs are especially missing. In this work, serum samples from pigs chronically exposed through their diet during 22 days to Aroclor 1260 (i.e. a commercially available mixture of NDL-PCBs) underwent a metabolomics analysis using gas chromatography-high resolution mass spectrometry (GC-HRMS), with the objective to investigate the effect of exposure to low doses of NDL-PCBs (few ng/kg body weight (b.w.) per day). The study showed that the serum profiles of 84 metabolites are significantly altered by the administration of Aroclor 1260, of which 40 could be identified at level 1. The aggregate interpretation of the results of this study, together with the outcome of a previous one involving LC-HRMS profiling, provided a substantial and concise overview of the effect of low dose exposure to NDL-PCBs, reflecting the hepatotoxic and neurotoxic effects already reported in literature at higher and longer exposures. These results are intended to contribute to the debate on the current toxicological reference values for these substances.

Exposure of the general French population to herbicides, pyrethroids, organophosphates, organochlorines, and carbamate pesticides in 2014-2016: Results from the Esteban study.

Esteban is a nationwide cross-sectional study conducted in France in 2014-2016, including 2503 adults aged 18-74 years old and 1104 children aged 6-17 years old, as part of the French Human Biomonitoring programme. The present paper describes the biological levels of five families of pesticides analysed on random sub-samples of 900 adults and 500 children for urine concentrations, and 759 adults and 255 children for serum concentrations, and the determinants of exposure. Organophosphates, carbamates and herbicides were measured in urine by UPLC-MS/MS; chlorophenols and pyrethroids were measured in urine by GC-MS/MS; specific organochlorines were measured in serum by GC-HRMS. Multivariate analyses were performed to identify the determinants of exposure using a generalized linear model. Pyrethroid metabolites were quantified in 99% of adults and children, with the exeption of F-PBA, which was quantified in 31% of adults and 27% of children, respectively. Carbamates and some specific organophosphates were barely or not quantified. DMTP was quantified in 82% of adults and 93% of children, and γ-HCH (lindane) was quantified in almost 50% of adults and children. Concentration levels of pesticide biomarkers were consistent with comparable international studies, except for ß-HCH, DMTP, and the deltamethrin metabolite Br2CA, whose levels were sometimes higher in France. Household insecticide use and smoking were also associated with higher levels of pyrethroids. All pyrethroids concentration levels were below existing health-based HBM guidance values, HBM-GVsGenPop, except for 3-PBA, for which approximately 1% and 10% of children were above the lower and upper urine threshold values of 22 µg/L and 6.4 µg/L, respectively. Esteban provides a French nationwide description of 70 pesticide biomarkers for the first time in children. It also describes some pesticide biomarkers for the first time in adults, including glyphosate and AMPA. For the latter, urine concentration levels were overall higher in children than in adults. Our results highlight a possible beneficial impact of existing regulations on adult exposure to organochlorine and organophosphate pesticides between 2006 and 2016, as concentration levels decreased over this period.

Persistent organochlorine pesticides in periprostatic adipose tissue from men with prostate cancer: Ethno-geographic variations, association with disease aggressiveness.

Although several studies have examined the relationship between organochlorine pesticides (OCPs) and prostate cancer (PCa) risk, no data are available concerning the association between OCPs concentrations in periprostatic adipose tissue (PPAT), which reflects cumulative exposure, and PCa aggressiveness. Moreover, no previous study has compared OCPs exposure in two distinct ethno-geographical populations. The objectives were to analyze OCPs in PPAT of PCa patients from either Mainland France or French West Indies in correlation with features of tumor aggressiveness, after adjusting for potential confounders such age, BMI, and polyunsaturated fatty acid (PUFA) content of PPAT. PPAT was analyzed in 160 patients (110 Caucasians and 50 African-Caribbeans), 80 with an indolent tumor (ISUP group 1 + pT2), and 80 with an aggressive tumor (ISUP group more than 3 + pT3). The concentrations of 29 OCPs were measured in PPAT concomitantly with the characterization of PUFA content. Exposure patterns of OCPs differed according to the ethno-geographical origin. Most OCPs were found at higher concentration in Caucasian patients, whereas pp'-DDE content was twice as high in African-Caribbeans. Chlordecone was only detected in PPAT from African-Caribbean patients. Most OCP concentrations were positively correlated with age, and some with BMI. After adjusting for age, BMI, and PUFA composition of PPAT, no significant association was found between OCPs content and risk of aggressive disease, except of mirex which appeared inversely associated with aggressive features of PCa in Caucasian patients. These results highlight a significant ethno-geographic variation in internal exposure to OCPs, which likely reflects differences in consumption patterns. The inverse relationship observed between mirex concentration and markers of PCa aggressiveness need to be further investigated.

Mixtures of persistent organic pollutants and ovarian function in women undergoing IVF.

RESEARCH QUESTION: Do internal levels of persistent organic pollutants (POP) in serum and follicular fluid affect ovarian function of women attending IVF? DESIGN: This cohort study included 136 women undergoing IVF in the assisted reproductive technology (ART) service of University Hospital from Nantes (France). Representative POP were measured using gas and liquid chromatography coupled with tandem mass spectrometry. Polyfluoroalkylated and perfluoroalkylated substances were measured in serum and polychlorinated biphenyls and organochlorinated pesticides in follicular fluid. Statistical associations between POP and ovarian reserve markers (anti-Müllerian Hormone [AMH] and antral follicle count [AFC], and ovarian responsiveness markers (Ovarian Sensitivity Index [OSI] and Follicular Output RaTe [FORT]), were explored in single and multipollutant regression models. RESULTS: Twenty-seven out of 53 POP congeners were frequently detected in almost all women attending IVF. Adjusted models did not show statistically significant associations between POP and ovarian reserve markers. Positive associations were found between some POP, i.e. hexachlorobenzene with FORT (ß 0.42, 95% CI 0.13 to 0.71, P = 0.005) or PCB52 with Ovarian Sensitivity Index (ß 0.22; 95% CI, 0.07 to 0.38, P = 0.005). Negative associations between some polyfluoroalkylated and perfluoroalkylated substances, PCB189 and trans-nonachlor with AFC and AMH were found among current smokers. CONCLUSIONS: Globally, associations between POP and the markers of ovarian function or responsiveness were lacking. Nonetheless, the stratification analysis suggested that current smoking could be a risk modifier, and extension of the study to a larger population sample size is needed.

Optimization and validation of a fast supercritical fluid chromatography tandem mass spectrometry method for the quantitative determination of a large set of PFASs in food matrices and human milk.

An Ultra-High Performance Supercritical Fluid Chromatography coupled with tandem Mass Spectrometry analytical method (UHPSFC-MS/MS) was developed for the determination of 34 perfluoroalkylated substances (PFASs) in food-related matrices. Two parameters (i.e. stationary phase and co-solvent) were selected and optimized using a step-by-step method, while a design of experiment (DoE) method using a central composite design (CCD) was implemented to optimize column temperature, mobile phase flow rate, co-solvent concentration and automated back pressure regulator (ABPR). The Torus 2-PIC column was selected along with ammonium acetate AcoNH4 as additive in the co-solvent. DoE optimization of both peak width and resolution enabled validating an optimized model (desirability 0.613) and setting column temperature at 38.7 °C, AcoNH4 concentration at 8 mM, mobile phase flow rate of 1.9 mL/min and ABPR at 1654 psi. The validated resulting method enabled reaching limits of quantification below 0.2 ng/g (w.w.) for 97 % PFASs in accordance with current EU requirements. The strategy was successfully applied to the characterization of a range (n > 30) of food-related matrices (red meat, poultry meat, eggs, fish and breast milk) collected in Algeria in 2019. PFOA and PFBA were observed as the most frequently detected PFASs, i.e. in 96.96 % and 90.9 % of the samples respectively. The highest concentrations were determined in fishery products up to 4.42 ng/g (w.w.) for PFTeDA and 0.75 ng/g (w.w.) for PFOS.

Nandrolone and estradiol biomarkers identification in bovine urine applying a liquid chromatography high-resolution mass spectrometry metabolomics approach.

With the aim of specifically investigating patterns associated with three steroid treatments (17ß-nandrolone, 17ß-estradiol, and 17ß-nandrolone + 17ß-estradiol) in bovine, an reversed phase liquid chromatography (RPLC)-electrospray ionization (ESI)(+/-)-high-resolution mass spectrometry (HRMS) study was conducted to characterize the urinary profiles of involved animals. Although specific fingerprints with strong differences could be highlighted between urinary metabolite profiles within urine samples collected on control and treated animals, it appeared further that significant discriminations could also be observed between steroid treatments, evidencing thus specific patterns and candidate biomarkers associated to each treatment. An MS-2 structural elucidation step enabled level-1 identification of two biomarkers mainly involved in energy pathways, in relation to skeletal muscle functioning. These results make it possible to envisage a global strategy for the detection of anabolic practices involving steroids, while at the same time providing clues as to the compounds used, which would facilitate the confirmation stage to follow.

Associations between Exposure to Organochlorine Chemicals and Endometriosis: A Systematic Review of Experimental Studies and Integration of Epidemiological Evidence.

BACKGROUND: Growing epidemiological evidence suggests that organochlorine chemicals (OCCs), including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), may play a role in the pathogenesis of endometriosis. OBJECTIVES: We aimed to systematically review the experimental evidence (in vivo and in vitro) on the associations between exposure to OCCs and endometriosis-related end points. METHODS: A systematic review protocol was developed following the National Toxicology Program /Office of Health Assessment and Translation (NTP/OHAT) framework and managed within a web-based interface. In vivo studies designed to evaluate the impact of OCCs on the onset or progression of endometriosis and proliferation of induced endometriotic lesions were eligible. Eligible in vitro studies included single-cell and co-culture models to evaluate the proliferation, migration, and/or invasion of endometrial cells. We applied the search strings to PubMed, Web of Science, and Scopus®. A final search was performed on 24 June 2020. Assessment of risk of bias and the level of evidence and integration of preevaluated epidemiological evidence was conducted using NTP/OHAT framework Results: Out of 812 total studies, 39 met the predetermined eligibility criteria (15 in vivo, 23 in vitro, and 1 both). Most studies (n=27) tested TCDD and other dioxin-like chemicals. In vivo evidence supported TCDD's promotion of endometriosis onset and lesion growth. In vitro evidence supported TCDD's promotion of cell migration and invasion, but there was insufficient evidence for cell proliferation. In vitro evidence further supported the roles of the aryl hydrocarbon receptor and matrix metalloproteinases in mediating steroidogenic disruption and inflammatory responses. Estrogen interactions were found across studies and end points. CONCLUSION: Based on the integration of a high level of animal evidence with a moderate level of epidemiological evidence, we concluded that TCDD was a known hazard for endometriosis in humans and the conclusion is supported by mechanistic in vitro evidence. Nonetheless, there is need for further research to fill in our gaps in understanding of the relationship between OCCs and their mixtures and endometriosis, beyond the prototypical TCDD. https://doi.org/10.1289/EHP8421.

Sustained bloodstream release of persistent organic pollutants induced by extensive weight loss after bariatric surgery: Implications for women of childbearing age.

BACKGROUND: Lipophilic persistent organic pollutants (POPs) are stored in adipose tissues and released in case of weight loss. OBJECTIVES: To analyze the kinetics and characteristics of this release during drastic weight loss after bariatric surgery and compare the results in case of women of childbearing age (WCBA) with critical blood concentration thresholds. METHODS: 100 morbidly obese patients (73 women including 53 of childbearing age and 27 men) were screened before and 3, 6 and 12 months after bariatric surgery for serum concentrations of 67 congeners or metabolites of banned or not yet banned organohalogenated persistent pollutants, including highly lipophilic polychlorobiphenyls (PCBs), organochlorine pesticides (OCPs), brominated flame retardants (BFRs), and less lipophilic perfluorinated alkylated substances (PFASs). RESULTS: Circulating levels of all chemicals, except PFASs, increased progressively after surgery, reaching after one year an increase between 30 and 139% compared to initial pre-surgical levels; median levels increased for PCB153 from 36.8 to 86.4 ng/g lw (+130%), for dichlorodiphenyldichloroethylene (p,p'-DDE) from 59.8 to 136.1 ng/g lw (+120%), and for hexachlorobenzene (HCB) from 9.8 to 20.3 ng/g lw (+110%). Weight loss averaging 30% of initial body weight at 12 months in both sexes (mean: 40.0 kg for men, 36.1 kg for women), was the main parameter related to the concentration increases (3.1 to 3.6% per kilogram weight loss). They were not dependent on initial BMI, presence of metabolic syndrome or type of surgical procedure but influenced by gender and biochemical properties such as degree of chlorination for PCBs and/or lipophilicity since PFASs did not increase at all. ∑PCB6 in blood after one year exceeded the critical concentration threshold for 24.5% women of childbearing age (13/53) versus 3.6% (2/53) before surgery. DISCUSSION: Massive weight loss within the first year following bariatric surgery is associated with a sustained increase of circulating lipophilic POPs. Short- and long-term consequences should be considered, mostly for childbearing age obese women, because of potential health risks for the future fetus and breastfeeding infant.

Auto-deconvolution and molecular networking of gas chromatography-mass spectrometry data.

We engineered a machine learning approach, MSHub, to enable auto-deconvolution of gas chromatography-mass spectrometry (GC-MS) data. We then designed workflows to enable the community to store, process, share, annotate, compare and perform molecular networking of GC-MS data within the Global Natural Product Social (GNPS) Molecular Networking analysis platform. MSHub/GNPS performs auto-deconvolution of compound fragmentation patterns via unsupervised non-negative matrix factorization and quantifies the reproducibility of fragmentation patterns across samples.

Adipose Tissue Properties in Tumor-Bearing Breasts.

The tissue stroma plays a major role in tumors' natural history. Most programs for tumor progression are not activated as cell-autonomous processes but under the conditions of cross-talks between tumor and stroma. Adipose tissue is a major component of breast stroma. This study compares adipose tissues in tumor-bearing breasts to those in tumor-free breasts with the intention of defining a signature that could translate into markers of cancer risk. In tumor-bearing breasts, we sampled adipose tissues adjacent to, or distant from the tumor. Parameters studied included: adipocytes size and density, immune cell infiltration, vascularization, secretome and gene expression. Adipose tissues from tumor-bearing breasts, whether adjacent to or distant from the tumor, do not differ from each other by any of these parameters. By contrast, adipose tissues from tumor-bearing breasts have the capacity to secrete twice as much interleukin 8 (IL-8) than those from tumor-free breasts and differentially express a set of 137 genes of which a significant fraction belongs to inflammation, integrin and wnt signaling pathways. These observations show that adipose tissues from tumor-bearing breasts have a distinct physiological status from those from tumor-free breasts. We propose that this constitutive status contributes as a non-cell autonomous process to determine permissiveness for tumor growth.

Human dietary exposure to chemicals in sub-Saharan Africa: safety assessment through a total diet study.

BACKGROUND: Human dietary exposure to chemicals can result in a wide range of adverse health effects. Some substances might cause non-communicable diseases, including cancer and coronary heart diseases, and could be nephrotoxic. Food is the main human exposure route for many chemicals. We aimed to assess human dietary exposure to a wide range of food chemicals. METHODS: We did a total diet study in Benin, Cameroon, Mali, and Nigeria. We assessed 4020 representative samples of foods, prepared as consumed, which covered more than 90% of the diet of 7291 households from eight study centres. By combining representative dietary surveys of countries with findings for concentrations of 872 chemicals in foods, we characterised human dietary exposure. FINDINGS: Exposure to lead could result in increases in adult blood pressure up to 2·0 mm Hg, whereas children might lose 8·8-13·3 IQ points (95th percentile in Kano, Nigeria). Morbidity factors caused by coexposure to aflatoxin B1 and hepatitis B virus, and sterigmatocystin and fumonisins, suggest several thousands of additional liver cancer cases per year, and a substantial contribution to the burden of chronic malnutrition in childhood. Exposure to 13 polycyclic aromatic hydrocarbons from consumption of smoked fish and edible oils exceeded levels associated with possible carcinogenicity and genotoxicity health concerns in all study centres. Exposure to aluminium, ochratoxin A, and citrinin indicated a public health concern about nephropathies. From 470 pesticides tested across the four countries, only high concentrations of chlorpyrifos in smoked fish (unauthorised practice identified in Mali) could pose a human health risk. INTERPRETATION: Risks characterised by this total diet study underscore specific priorities in terms of food safety management in sub-Saharan Africa. Similar investigations specifically targeting children are crucially needed. FUNDING: Standards and Trade Development Facility.

Undernutrition combined with dietary mineral oil hastens depuration of stored dioxin and polychlorinated biphenyls in ewes. 1. Kinetics in blood, adipose tissue and faeces.

Food safety crises involving persistent organic pollutants [POPs, e.g. dioxins, polychlorinated biphenyls (PCBs), organochlorine pesticides] lead to systematic slaughter of livestock to prevent their entry into the food chain. Therefore, there is a need to develop strategies to depurate livestock moderately contaminated with POPs in order to reduce such economic and social damages. This study aimed to test a POPs depuration strategy based on undernutrition (37% of energy requirements) combined with mineral oil (10% in total dry matter intake) in nine non-lactating ewes contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and PCBs 126 and 153. In order to better understand the underlying mechanisms of the depuration process, POPs kinetics and body lipids dynamics were followed concomitantly over 57-day of depuration in POPs storage (adipose tissue, AT), central distribution (blood) and excretion (faeces) compartments. Faecal POPs concentrations in underfed and mineral oil supplemented ewes increased by 2.0 to 2.6-fold, but not proportionally to lipids concentration which increased by 6-fold, compared to the control ewes. Nonetheless, after 57 days of depuration in undernutrition and mineral oil supplementation, AT POPs concentrations were 1.5 to 1.6-fold higher while serum concentrations remained unchanged compared to the control ewes. This was concomitant with a decrease by 2.7-fold of the AT estimated lipids weight along the depuration period. This reduction of the volume of the storage compartment combined with the increase of POPs faecal excretion in underfed and mineral oil supplemented ewes led to a reduction by 1.5-fold of the PCB 126 AT burden, while no changes were observed for TCDD and PCB 153 burdens (vs. no change for PCB 126 and increases for TCDD and PCB 153 AT burdens in control ewes). The original approach of this study combining the fine description at once of POPs kinetic and of body lipids dynamic improved our understanding of POPs fate in the ruminant.

Undernutrition combined with dietary mineral oil hastens depuration of stored dioxin and polychlorinated biphenyls in ewes. 2. Tissue distribution, mass balance and body burden.

Food safety crises involving persistent organic pollutants (POPs) lead to systematic slaughter of livestock to prevent contaminants from entering the food chain. Therefore, there is a need to develop strategies to depurate livestock moderately contaminated with POPs to reduce economic and social damage. This study aimed to test undernutrition (37% of energy requirements) combined with mineral oil (10% in total dry matter intake) in nine non-lactating ewes contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) 126 and 153 as a strategy to enhance the depuration of POPs through faecal excretion. To better understand the underlying mechanisms of the depuration process, lipophilic POPs and lipid fluxes were co-monitored in various body and excretion compartments. Body compartments (adipose tissues, muscle, liver and blood) and the total empty body were analyzed for lipids and POPs concentrations and burdens at slaughter, as well as excretion compartments (faeces and wool) collected during the depuration period. Decreases in empty body total and lipid weights were 6-fold higher in underfed and supplemented ewes compared to control ewes. In addition, over the depuration period undernutrition and supplementation treatment increased faecal TCDD, PCBs 126 and 153 excretions by 1.4- to 2.1-fold but tended to decrease wool PCB 153 excretion by 1.4-fold. This induced 2- to 3-fold higher decreases in the empty body POPs burdens for underfed and supplemented ewes. Nonetheless, when expressed relative to the calculated initial empty body burdens, burdens at slaughter decreased only slightly from 97%, 103% and 98% for control ewes to 92%, 97% and 94% for underfed and supplemented ones, for TCDD, PCBs 126 and 153, respectively. Fine descriptions at once of POPs kinetic (companion paper 1) and mass balance (companion paper 2), and of body lipid dynamics were very useful in improving our understanding of the fate of POPs in the ruminants.

A method to assess lifetime dietary risk: Example of cadmium exposure.

Usually health risk related to food contaminants is assessed based on consumption data collected on a few days. Consequently, this approach considers neither the evolution of exposures over time nor the potential accumulation of the substance. The aim of the present study was to develop a method to assess lifetime dietary risk due to cadmium exposure. Three methods were compared, respectively based on age, dietary pattern and sociodemographic characteristics. Additionally, exposure trajectories were converted into cadmium body burden trajectories using a PBTK-TD model ultimately predicting the occurrence of renal effects. It was shown that dietary exposures to cadmium, as well as exceedances of health based guidance values, greatly vary with age and individual profiles. The developed methods allowed identifying parameters affecting dietary exposure to cadmium and distinguishing at-risk subpopulations. Furthermore, this study demonstrated that it is necessary to consider individual changes through life and kinetic of the substance to assess risk properly.

Levels of persistent organic pollutants (POPs) in foods from the first regional Sub-Saharan Africa Total Diet Study.

For the first time, a multi-centre Total Diet Study was carried out in Benin, Cameroon, Mali and Nigeria. We collected and prepared as consumed 528 typical fatty foods from those areas and pooled these subsamples into 44 composites samples. These core foods were tested for a wide spectrum of POPs, including polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), brominated flame-retardants (BFRs), organochlorine compounds (OCs), perfluoro alkyl substances (PFAS) and chlorinated flame retardants (CFRs). The POPs contamination levels were similar or lower than those reported in total diet studies previously conducted worldwide. In most cases, core foods belonging to fish food group presented higher POPs concentrations than the other food groups. Interestingly, we observed a difference in both contamination profile and concentration for smoked fish compared to non-smoked fish. Such finding suggests that the smoking process itself might account for a large proportion of the contamination. Further investigation would require the assessment of combustion materials used to smoke fish as a potential vehicle, which may contribute to the dietary exposure of the studied populations to POPs.

WiPP: Workflow for Improved Peak Picking for Gas Chromatography-Mass Spectrometry (GC-MS) Data.

Lack of reliable peak detection impedes automated analysis of large-scale gas chromatography-mass spectrometry (GC-MS) metabolomics datasets. Performance and outcome of individual peak-picking algorithms can differ widely depending on both algorithmic approach and parameters, as well as data acquisition method. Therefore, comparing and contrasting between algorithms is difficult. Here we present a workflow for improved peak picking (WiPP), a parameter optimising, multi-algorithm peak detection for GC-MS metabolomics. WiPP evaluates the quality of detected peaks using a machine learning-based classification scheme based on seven peak classes. The quality information returned by the classifier for each individual peak is merged with results from different peak detection algorithms to create one final high-quality peak set for immediate down-stream analysis. Medium- and low-quality peaks are kept for further inspection. By applying WiPP to standard compound mixes and a complex biological dataset, we demonstrate that peak detection is improved through the novel way to assign peak quality, an automated parameter optimisation, and results in integration across different embedded peak picking algorithms. Furthermore, our approach can provide an impartial performance comparison of different peak picking algorithms. WiPP is freely available on GitHub (https://github.com/bihealth/WiPP) under MIT licence.

Sub-Saharan Africa total diet study in Benin, Cameroon, Mali and Nigeria: Pesticides occurrence in foods.

In the framework of the first regional Total Diet Study in Sub-Saharan Africa, 3696 foodstuffs, commonly consumed in Benin, Cameroon, Mali and Nigeria were purchased, prepared as consumed and pooled into 308 composite samples. Those core foods were tested for up to 470 pesticides residues by liquid and gas chromatography coupled with tandem mass spectrometry. 39 pesticides were detected with 294 total occurrences, including 47.3% organophosphate pesticides and 35.7% pyrethroids. More specifically, 6 substances represented 75.5% of all 3 organophosphates and 3 pyrethroids: chlorpyrifos (22.4%) cypermethrin (18.0%) dichlorvos (13.6%), lambda cyhalothrin (8.2%), permethrin (7.5%) and profenofos (5.8%). One pesticide or more was detected in 45.8% of samples. Strikingly, several pesticides were quantified in 2 composite samples of smoked fish from Mali: chlorpyrifos (5236-18 084 µg/kg), profenofos (30-182 µg/kg), cypermethrin (22-250 µg/kg), cyfluthrin (16-117 µg/kg), lambda cyhalothrin (9-17 µg/kg) and permethrin (3-6 µg/kg).

Associations between persistent organic pollutants and risk of breast cancer metastasis.

BACKGROUND: Breast cancer (BC) is a major public health concern with over 2 million new cases diagnosed and over 600,000 deaths in 2018 in women worldwide. When distant metastases are present at diagnosis, the 5-year survival rate is only 26%. Recent studies have suggested that persistent organic pollutants (POPs) that accumulate in adipose tissue (AT) can influence tumor phenotype and stimulate cellular processes important for metastasis such as invasion. We, therefore, tested the hypothesis that POP exposure is associated with BC metastasis. METHODS: We conducted an exploratory case-control study in which the concentrations of 49 POPs were measured in both AT and serum samples from BC patients, with or without lymph node metastasis, who underwent partial or total mastectomies, lymph node biopsies and sampling of the adipocytic tumor microenvironment. Adjusted, unconditional logistic models were used to study the associations between the POP concentrations and the risk of metastasis and other hallmarks of cancer aggressiveness. RESULTS: 2.3.7.8-TCDD concentrations in AT are positively associated with the risk of metastasis in 43 patients who have BMIs equal or higher than 25 kg/m2 (odds ratio: 4.48 (1.32-20.71)). Furthermore, the concentrations of 2.3.7.8-TCDD and two coplanar PCBs (77&169) in AT also were positively associated with the risk of lymph node metastasis and the tumor size. CONCLUSION: Our study suggests that 2.3.7.8-TCDD and some PCBs contribute to the development of tumor metastasis and other hallmarks of cancer aggressiveness. While these results should be considered with caution, this is the first study to identify such potential risk factors. Larger longitudinal studies are necessary to confirm our results. Clinical Trial Protocol Record: 2013-A00663-42.

French infant total diet study: Dietary exposure to heat-induced compounds (acrylamide, furan and polycyclic aromatic hydrocarbons) and associated health risks.

A total diet study (TDS) was conducted between 2010 and 2016 to assess the risk associated with chemicals in food of non-breast-fed children from 1 to 36 months living in France. Food samples were collected, prepared "as consumed", and analyzed for chemicals of public health interest. Acrylamide, furan and polycyclic aromatic hydrocarbons (PAHs) were analyzed as heat-induced compounds produced mainly during thermal processing of foods. Dietary exposure was assessed for 705 representative children using food consumptions recorded through a 3-consecutive-days record. As all calculated margins of exposure (MOE) for PAHs exceeded 10 000, dietary exposure of the infant and toddler population was deemed tolerable with regard to the carcinogenic risk. Conversely, the exposure levels to acrylamide and furan were considered as of concern, requiring management measures to reduce the exposure essentially by reducing the formation of heat-induced compounds during food production or preparation processes. Efforts should mainly focus on major contributors to the exposure, i.e. sweet and savoury biscuits and bars, and potatoes and potato products for acrylamide, baby jars of vegetables, with or without meat or fish for acrylamide and furan.