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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

Background: Endometriosis is a gynaecological disease characterized by the presence of ectopic endometrial tissue that affects women during their reproductive years, having a strong impact on their lives, fertility and healthcare costs. The aetiology remains largely unknown, but current evidence suggests that it is multi-causal and oestrogen-dependent. Many epidemiologic studies have explored associations between organochlorine chemicals (OCCs) and endometriosis, but the findings are inconsistent. Objectives: A systematic review (SR) and meta-analysis were conducted to gather and synthesize all the available evidence from human epidemiological studies about the associations between OCCs and endometriosis. Data sources: The searches were conducted in PubMed and Web of Science in June 2016 with a final follow-up in August 2018. Study eligibility criteria: Only human epidemiological studies were considered, independent of participant age, body mass index or life-stage. Studies reporting individual measures of exposure to OCCs were included, considering but not limited to polychlorinated dibenzodioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), or organochlorine pesticides (OCPs). The primary health outcome was presence of endometriosis, including all sub-types. Eligibility criteria excluded articles not written in English, conference papers, reviews and studies with overlapping information. Study appraisal and synthesis methods: A SR protocol pre-registered at PROSPERO was applied in duplicate to gather and extract all eligible original papers from PUBMED and Web of Science databases. Odds ratios were pooled using the inverse variance method for random effects meta-analysis for each group of OCCs. Risk of bias was assessed using the National Toxicology Program/Office of Health Assessment and Translation (NTP/OHAT) Risk of Bias Rating Tool for Human and Animal Studies adapted to the review question. The confidence in the body of evidence and related level of evidence was measured by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) based NTP/OHAT framework. The results were structured and presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Of the 51 studies retained for the full-text screening, 17 provided effect sizes and metrics sufficient for pooling estimates through meta-analysis. The overall odds ratios and 95% confidence intervals were 1.65 (1.14; 2.39) for dioxins (n = 10), 1.70 (1.20; 2.39) for PCBs (n = 9), and 1.23 (1.13; 1.36) for OCPs (n = 5). Despite being statistically significant, these estimates should be considered with caution given the notable heterogeneity and small estimated effect size. Misclassification of exposure, due to varying laboratory detection rate capabilities, and disease status, due to varying definitions of endometriosis, were identified as major sources of uncertainty. Limitations, conclusions, and implications of key findings: The level of evidence was considered to be “moderate” with “serious” risk of bias according the NTP/OHAT criteria, supporting the need for further well-designed epidemiological research to fill lingering data gaps. Given the complexity of endometriosis and lack of known biomarkers suitable for population-based research, carefully designed observational studies play an important role in better understanding the aetiology of endometriosis, as will evolving mixture modeling approaches capable of handling various environmental chemical exposures. Attention to critical windows of exposure will shed further light on the possible developmental origin of endometriosis. Considering the high economic and societal cost associated with endometriosis, further research on this field is urged. Systematic review registration number: CRD42018080956 Keywords: Endometriosis, Endocrine-disrupting chemicals, Dioxins, Polychlorinated biphenyls, Biomarkers, Meta-analysis

Humans are exposed daily to complex mixtures of chemical pollutants through their environment and diet, some of which have the potential to disrupt the bodies’ natural endocrine functions and contribute to reproductive diseases like endometriosis. Increasing epidemiological and experimental evidence supports the association between endometriosis and certain persistent organic pollutants (POPs) like dioxins; however, little is known about the underlying linking mechanisms. The main objective of this study is to proof the methodological applicability and discovery potential of integrating ultra-trace mass spectrometry (MS) profiling of POP biomarkers and endogenous biomarker profiling (MS metabolomics and cytokines) in a case-control study for the etiological research of endometriosis. The approach is applied in a pilot clinical-based study conducted in France where women with and without surgically confirmed endometriosis were recruited. Serum samples were analysed with high-resolution MS for about 30 polychlorinated biphenyls (PCBs), organochlorinated pesticides and perfluoroalkyl substances (PFAS). About 600 serum metabolites and lipids were identified with targeted metabolomics using tandem MS with the Biocrates MxP® Quant 500 Kit. A panel of 4 pro-inflammatory cytokines were analysed using ELISA-based 4-PLEX analyser. Statistical analysis included a battery of variable selection approaches, multivariate logistic regression for single-chemical associations, Bayesian kernel machine regressions (BKMR) to identify mixture effects of POPs and a multiblock approach to identify shared biomarker signatures among high risk clusters. The results showed the positive associations between some POPs and endometriosis risk, including the pesticide trans-nonachlor Odds Ratio (95% Confidence Interval) 3.38 (2.06–5.98), p

The impact of environmental chemicals like persistent organic pollutants (POPs) on reproductive health is still poorly understood, despite the high societal and economical costs. The aim of the present study was to systematically review and evaluate the human evidence on the associations between internal levels of POPs and in vitro Fertilization (IVF) outcomes among women. We applied a protocol based on the National Toxicology Program Office of Health Assessment and Translation's guidelines for the study search, selection and quality assessment. Fifteen studies were finally retained in the present work. The results showed that main families of POPs are still pervasive in follicular fluid and serum of women undergoing IVF treatments. Globally, we found inconsistent findings across studies for specific exposure-outcome dyads, suggesting that adverse effects of POPs on IVF outcomes cannot be ruled out. Specifically, there is evidence that POPs, notably some polychlorinated biphenyls and organochlorine pesticides, may impair embryo quality and pregnancy rates. Most studies have been performed in small cohorts (n

Endometriosis is a gynaecological disease characterised by the presence of endometriotic tissue outside of the uterus impacting a significant fraction of women of childbearing age. Evidence from epidemiological studies suggests a relationship between risk of endometriosis and exposure to some organochlorine persistent organic pollutants (POPs). However, these chemicals are numerous and occur in complex and highly correlated mixtures, and to date, most studies have not accounted for this simultaneous exposure. Linear and logistic regression models are constrained to adjusting for multiple exposures when variables are highly intercorrelated, resulting in unstable coefficients and arbitrary findings. Advanced machine learning models, of emerging use in epidemiology, today appear as a promising option to address these limitations. In this study, different machine learning techniques were compared on a dataset from a case-control study conducted in France to explore associations between mixtures of POPs and deep endometriosis. The battery of models encompassed regularised logistic regression, artificial neural network, support vector machine, adaptive boosting, and partial least-squares discriminant analysis with some additional sparsity constraints. These techniques were applied to identify the biomarkers of internal exposure in adipose tissue most associated with endometriosis and to compare model classification performance. The five tested models revealed a consistent selection of most associated POPs with deep endometriosis, including octachlorodibenzofuran, cis-heptachlor epoxide, polychlorinated biphenyl 77 or trans-nonachlor, among others. The high classification performance of all five models confirmed that machine learning may be a promising complementary approach in modelling highly correlated exposure biomarkers and their associations with health outcomes. Regularised logistic regression provided a good compromise between the interpretability of traditional statistical approaches and the classification capacity of machine learning approaches. Applying a battery of complementary algorithms may be a strategic approach to decipher complex exposome-health associations when the underlying structure is unknown.

International audience; The use of exposure biomarkers has been growing during the last decades, being considered the 'gold-standard' approach for individual exposure assessment to environmental chemicals. However, lipophilic endocrine disrupting chemicals (LEDC) have specific physicochemical and biological properties implying particular analytical challenges and interpretative caveats. The epidemiological literature is therefore afflicted by methodological inconsistencies and results divergences, in part due to recognised sources of exposure measurement error and misinterpretation of results. The aim of the present review is to identify external and endogenous sources of variability and uncertainty associated with the LEDC blood biomarkers in epidemiological studies. The dynamic nature of blood and an overview of the known mechanisms of transport, storage and partition of LEDCs in the organism are first described. The external sources of variability and uncertainty introduced at pre-analytical and analytical level are subsequently presented. Subsequently, we present some specific cases where the dynamics of lipids and LEDCs may be substantially modified and thus, the interpretation of biomarkers can be particularly challenging. The environmental obesogens as source of biomarkers variability is also discussed in the light of the most recent findings. Finally, different modelling approaches (statistical and pharmacokinetic models) proposed to improve the use and interpretation of biomarkers are appraised.

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. Keywords: Breast cancer, Environmental exposure, Adipose tissue, Serum, Organochlorine pesticides, Endocrine disrupting chemicals, Polychlorinated biphenyls, Perfluoroalkyl acid, Dioxins

Background: Endometriosis is a hormone-dependent gynaecological disease characterised by the presence and growth of endometrial tissues outside of the uterus. There is growing experimental evidence that suggests environmental endocrine disrupting chemicals, specifically organochlorine chemicals (OCCs), may play a role in the pathogenesis of endometriosis, but to date, there are no studies attempting to gather and synthesise the published literature systematically. Objectives: The main objective of this SR is to evaluate the associations between the exposure to OCCs and endometriosis in experimental models (in vivo and in vitro). Methods: The SR framework has been developed following the guidelines established in National Toxicology Program/ Office of Health Assessment and Translation (NTP/OHAT) Handbook for Conducting a Literature-Based Health Assessment, which provides a standardised methodology to implement the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to environmental health assessments. The review process will be managed and documented through HAWC, an open-source content management system, to guarantee transparency. Eligibility criteria: Only experimental studies, in vivo, ex vivo or in vitro, exploring associations between controlled exposures to OCCs and endometriosis and related outcomes will be included. Eligible studies will include peer reviewed articles of any publication date which are sources of primary data. Only studies published in English will be considered. Information sources: We will apply the search strings to the scientific literature databases NCBI PubMed, Web of Science and SCOPUS. Manual searches will be performed through the list of references of included articles. Data extraction and synthesis or results: Data will be extracted according to a pre-defined set of forms and synthesised in a narrative report. Given sufficient commensurate data, a meta-analysis may also be performed. Risk of bias: A quality assessment will be performed for in vivo and in vitro studies using the NTP/OHAT Risk of Bias Rating Tool for Human and Animal Studies. Level of evidence rating: Following a comprehensive assessment of the quality of evidence for both in vivo and in vitro studies, a confidence rating will be assigned to the body of literature and subsequently translated into a rating on the level of evidence (high, moderate, low, or inadequate) regarding the research question.Systematic review registration: PROSPERO CRD42018102618. Keywords: Endometriosis, Organochlorine, Dioxins, Endocrine disrupting chemicals, In vivo, In vitro, Systematic review

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.

International audience; Endocrine-disrupting chemicals are proposed to increase breast cancer (BC) incidence. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), two perfluorinated alkylated substances (PFASs), are suspected to be ubiquitously present in the blood of human population worldwide. We investigated the associations between serum concentrations of these substances and BC risk. Etude Epidémiologique auprès de femmes de l'Education Nationale is a cohort of 98,995 French women born in 1925-1950 and followed up since 1990. We sampled 194 BC cases and 194 controls from women with available blood samples. Serum concentrations of PFASs were measured by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Adjusted conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two sided. While PFASs concentrations were not associated with BC risk overall, we found positively linear associations between PFOS concentrations and the risk of ER+ (3rd quartile: OR = 2.22 [CI = 1.05-4.69]; 4th quartile: OR = 2.33 [CI = 1.11-4.90]); Ptrend = 0.04) and PR+ tumors (3rd quartile: OR = 2.47 [CI = 1.07-5.65]; 4th quartile: OR = 2.76 [CI = 1.21-6.30]; Ptrend = 0.02). When considering receptor-negative tumors, only the 2nd quartile of PFOS was associated with risk (ER-: OR = 15.40 [CI = 1.84-129.19]; PR-: OR = 3.47 [CI = 1.29-9.15]). While there was no association between PFOA and receptor-positive BC risk, the 2nd quartile of PFOA was positively associated with the risk of receptor-negative tumors (ER-: OR = 7.73 [CI = 1.46-41.08]; PR-: OR = 3.44 [CI = 1.30-9.10]). PFAS circulating levels were differentially associated with BC risk. While PFOS concentration was linearly associated with receptor-positive tumors, only low concentrations of PFOS and PFOA were associated with receptor-negative tumors. Our findings highlight the importance of considering exposure to PFASs as a potential risk factor for BC.

International audience; The gold-standard matrix for measuring the internal levels of persistent organic pollutants (POPs) is the adipose tissue, however in epidemiological studies the use of serum is preferred due to the low cost and higher accessibility. The interpretation of serum biomarkers is tightly related to the understanding of the underlying causal structure relating the POPs, serum lipids and the disease. Considering the extended benefits of using serum biomarkers we aimed to further examine if through statistical modelling we would be able to improve the use and interpretation of serum biomarkers in the study of endometriosis. Hence, we have conducted a systematic comparison of statistical approaches commonly used to lipid adjust the circulating biomarkers of POPs based on existing methods, using data from a pilot case control study focused on severe deep infiltrating endometriosis. The odds ratios (ORs) obtained from unconditional regression for those models with serum biomarkers were further compared to those obtained from adipose tissue. The results of this exploratory study did not support the use of blood biomarkers as proxy estimates of POPs in adipose tissue to implement in risk models for endometriosis with the available statistical approaches to correct for lipids. The current statistical approaches commonly used to lipid-adjust circulating POPs, do not fully represent the underlying biological complexity between POPs, lipids and disease (especially those directly or indirectly affecting or affected by lipid metabolism). Hence, further investigations are warranted to improve the use and interpretation of blood biomarkers under complex scenarios of lipid dynamics.

Background: The prevalence of obesity is increasing in all countries, becoming a substantial public health concern worldwide. Increasing evidence has associated obesity with persistent pollutants such as the pesticide DDT and its metabolite p,p′-DDE. Objectives: Our objective was to systematically review the literature on the association between exposure to the pesticide DDT and its metabolites and obesity to develop hazard identification conclusions. Methods: We applied a systematic review-based strategy to identify and integrate evidence from epidemiological, in vivo, and in vitro studies. The evidence from prospective epidemiological studies was quantitatively synthesized by meta-analysis. We rated the body of evidence and integrated the streams of evidence to systematically develop hazard identification conclusions. Results: We identified seven epidemiological studies reporting prospective associations between exposure to p,p′-DDE and adiposity assessed by body mass index (BMI) z-score. The results from the meta-analysis revealed positive associations between exposure to p,p′-DDE and BMI z-score (β=0.13 BMI z-score (95% CI: 0.01, 0.25) per log increase of p,p′-DDE). Two studies constituted the primary in vivo evidence. Both studies reported positive associations between exposure to p,p′-DDT and increased adiposity in rodents. We identified 19 in vivo studies and 7 in vitro studies that supported the biological plausibility of the obesogenic effects of p,p′-DDT and p,p′-DDE. Conclusions: We classified p,p′-DDT and p,p′-DDE as “presumed” to be obesogenic for humans, based on a moderate level of primary human evidence, a moderate level of primary in vivo evidence, and a moderate level of supporting evidence from in vivo and in vitro studies. https://doi.org/10.1289/EHP527

The presence of two main mycotoxins, ochratoxin A (OTA) and deoxynivalenol (DON), is widespread in cereal-based foodstuffs marketed in Europe. The objectives of this study were to develop and validate a multi-detection analytical methodology to simultaneously assess the urinary concentrations of OTA, DON and their metabolites, and to apply this methodology in a preliminary follow-up trial in Catalonia (Spain). Hence, an ultra-performance liquid chromatography with tandem mass spectrometry method was developed to simultaneously assess the urinary levels of OTA, DON, deoxynivalenol-3-glucoside (DON-3-glucoside), deoxynivalenol-3-glucuronide (DON-3-glucuronide), 3-acetyldeoxynivalenol (3-ADON) and de-epoxy-deoxynivalenol (DOM-1). Urine mycotoxins levels and food dietary intake were prospectively monitored in a group of volunteers throughout a restriction period followed by a free-diet period. The proposed multi-detection methodology for urinary OTA and DON metabolites was validated, providing suitable recovery, linearity and precision. The results from the pilot trial showed that urinary OTA, DON and its metabolites were detected in most background samples, displaying moderate reductions after the restriction period and subsequently recovering the background levels. Despite the restriction period, some DON metabolites, such as 3-ADON or DOM-1, were still found in urine samples, placing alternative sources of DON exposure other than the ones considered in the study under suspicion. DON and DON-3-glucuronide were significantly associated with consumption of bread, pasta and pastries, while OTA was only associated with consumption of wine and breakfast cereals. The urinary levels of OTA were significantly correlated with plasmatic levels of OTA and ochratoxin α, supporting the results from the multidetection method in urine. The results also showed that the high exposure to DON could be held throughout the time by the same person, exceeding the tolerable daily intake systematically instead of eventually. The estimates of OTA exposure through urine are largely higher than those obtained with the dietary approach. The background levels found in urine revealed that the exposure to DON and OTA could be of concern for the Catalonian population, thus, further studies applying this biomonitoring methodology in a larger sample of Catalonian population are needed to accurately characterise the human health risks at population level.

Ochratoxin A (OTA) as well as its metabolite ochratoxin α (OTα) were detected in human urine in order to assess the exposure to OTA of a group of 72 adult inhabitants of the city of Lleida (Spain). Urine samples were enzymatically treated; OTA and OTα were separated by liquid–liquid extraction, and detected by HPLC-fluorescence. Exposure to OTA was also evaluated by the estimation of its daily intake from food contamination data from the literature and from food consumption data provided by the participants, who filled in a food frequency questionnaire (FFQ) and a three-day food consumption record (3DR). OTA occurrence (12.5%, limit of detection = 0.034 ng/mL) was lower than OTα occurrence (61.1%, limit of detection = 0.023 ng/mL). The range of concentrations was 0.057–0.562 ng/mL and 0.056–2.894 ng/mL for OTA and for OTα, respectively. It could be observed for positive samples that the FFQ data were related to the OTA concentration in urine, whereas the 3DR data were related to the OTα levels in urine. The OTA estimated daily intake of the participants was lower than 30% of the latest provisional tolerable daily intake of 14 ng/kg body weight/day in the worst cases of exposure.

Consumption of seafood is one of the most relevant pathways of exposure to environmental pollutants present in food. The list of toxic compounds in seafood is very extensive, including heavy metals, polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs). In order to quantify the importance of the problem, tools to combine and simplify large data collections are mandatory for risk managers and decision-makers. In this study, the development of a prioritization setting focusing on chemical hazards taken up through seafood was aimed. For this purpose, the toxicity data of several chemicals was integrated with concentration and seafood consumption data, building an integrated risk index for seafood contaminants (IRISC) able to draw a map of risk for each chemical and family of chemicals. A pilot trial was performed on a sample of 74 pollutants, four seafood species and five European countries (Belgium, Ireland, Italy, Portugal and Spain). The preliminary results revealed that Portugal and Spain presented the highest IRISC, while Belgium was the region with the lowest IRISC. The contribution of each group of contaminants to the IRISC was very similar among countries, with heavy metals being the major contributor, followed by PCBs, PCDD/Fs and endocrine disrupting compounds. When the contribution of different seafood species to the Risk Indexes (RIs) was compared, the results elucidated the high input from sardines, showing the highest rates (54.9-76.1) in the five countries. The IRISC provides a friendly approach to the chemical risk scene in Europe, establishing normalized prioritization criteria considering toxicity and consumption as well as concentration of each chemical.

Marine pollution gives rise to concern not only about the environment itself but also about the impact on food safety and consequently on public health. European authorities and consumers have therefore become increasingly worried about the transfer of contaminants from the marine environment to seafood. So-called "contaminants of emerging concern" are chemical substances for which no maximum levels have been laid down in EU legislation, or substances for which maximum levels have been provided but which require revision. Adequate information on their presence in seafood is often lacking and thus potential risks cannot be excluded. Assessment of food safety issues related to these contaminants has thus become urgent and imperative. A database (www.ecsafeseafooddbase.eu), containing available information on the levels of contaminants of emerging concern in seafood and providing the most recent data to scientists and regulatory authorities, was developed. The present paper reviews a selection of contaminants of emerging concern in seafood including toxic elements, endocrine disruptors, brominated flame retardants, pharmaceuticals and personal care products, polycyclic aromatic hydrocarbons and derivatives, microplastics and marine toxins. Current status on the knowledge of human exposure, toxicity and legislation are briefly presented and the outcome from scientific publications reporting on the levels of these compounds in seafood is presented and discussed The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under the EC safe SEAFOOD project (Grant agreement no.311820)

The goals of the present work were, on the one hand, to assess the effect of baking on the stability of zearalenone (ZEA) and deoxynivalenol (DON), as well as the transfer of DON from pasta to boiling water, and, on the other hand, to quantify the impact of DON depletion, during cooking of pasta, on overall exposure estimates. Therefore, the bread-making process was simulated on a pilot-plant scale by using naturally contaminated flour with DON and ZEA. Transfer of DON from pasta to water was evaluated at different boiling times. Pasta was prepared on a pilot-plant scale by using naturally contaminated durum wheat flour; subsequently, it was boiled simulating home cooking. The experiments examined the stability of DON and ZEA during the bread-making process, including fermentation with Saccharomyces cerevisiae and baking at 200°C. Our results showed a high transfer of DON from pasta to boiling water, reaching depletion levels of almost 75%, which correlated with levels found in water. Accordingly, these cooking depletion rates were computed through a stochastic exposure model to weight their impact on the final exposure estimates. Finally, statistically significant differences were found in most of the parameters and populations assessed, but these were not enough to consider the process as protective because the contribution of pasta to the overall DON intake was commonly low.

Ochratoxin A (OTA) was analysed in composite samples of cereal-based baby foods, beer, breakfast cereals (corn- and rice and wheat-based), loaf bread, peanuts and pistachios. Foodstuffs were collected in hypermarkets and supermarkets from 12 cities in the Spanish region of Catalonia, and composite samples were prepared for analysis involving liquid–liquid extraction, followed by immunoaffinity column clean-up and HPLC with fluorescence detection. Consumption data for the selected foodstuffs were collected by means of a food-frequency questionnaire. The studied population was grouped by age in infants, children, adolescents and adults; and exposure to OTA through the specified foodstuffs, and through wine and coffee, was assessed. Exposure assessment was done through deterministic and probabilistic modelling of the contamination and consumption data. OTA occurrence and mean of positive samples (ng g−1 or ng ml−1, for beer) were the following: 8.7% and 0.233 in baby foods; 88.7% and 0.022 in beer; 2.8% and 0.728 in corn-based breakfast cereals; 25% and 0.293 in wheat-based breakfast cereals; 12.9% and 0.283 in loaf bread; 41.7% and 0.241 in peanuts; and 2.9% and 0.228 in pistachios. The median estimated daily intake of OTA through the foodstuffs by each age group were below the latest provisional tolerable daily intakes (PTDIs) of 17 and 14 ng kg−1 bw day−1 recommended by the European Food Safety Authority (EFSA) in 2006 and the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 2007, respectively, ranging from 1% and 2% of those values in adolescents and children, to 3% and 11% in adults and infants. The authors are grateful to the Spanish Government (CICYT, Comisión Interministerial de Ciencia y Tecnología, Project AGL 2008-05030-C02-01) and to the Catalonian Food Safety Agency of the Generalitat de Catalunya Health Department for funding this work in the framework of a safety programme to assess the exposition of the Catalonian population to mycotoxins. M.B. Coronel thanks the Comissionat per a Universitats i Recerca del Departament d’Innovació , Universitats i Empresa of the Generalitat de Catalunya and the European Social Fund for the pre-doctoral grant.

International audience; The mycotoxin deoxynivalenol (DON) is one of the most common contaminants of cereals worldwide, and its occurrence has been widely reported in raw foods and foodstuffs, around the European region, including Catalonia. In the present work, a stochastic methodology has been applied to accurately assess the exposure of the Catalonian population (Spain) to DON through food consumption. Raw contamination data was provided by a large survey conducted in this region, in addition to the raw consumption data from a nutritional study specifically designed to assess the dietary intake of the main foodstuffs related to DON contamination for all population age groups. Contamination and consumption data were combined by simulation using an essentially parametric (P-P) method. The P-P method draws sampling values from distribution functions fitted to consumption and contamination datasets. Moreover, to quantify the accuracy and reliability of the statistics estimates, we built the related confidence intervals using a Pseudo-Parametric bootstrap method. Considering the results drawn from the P-P simulation method, the Catalonian population should be expected to be exposed at moderated levels of deoxynivalenol, the infants and individuals with ethnic dietary patterns being the most exposed population groups