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Abstract: Owing to the intensive use of pesticides and their potential persistence in the environment, various pesticide residues can be found in the diet. Consumers are therefore exposed to complex pesticide mixtures which may have combined adverse effects on human health. By modelling food exposure to multiple pesticides, this paper aims to determine the main mixtures to which the general population is exposed in France. Dietary exposure of 3337 individuals from the INCA2 French national consumption survey was assessed for 79 pesticide residues, based on results of the 2006 French food monitoring programmes. Individuals were divided into groups with similar patterns of co-exposure using the clustering ability of a Bayesian nonparametric model. In the 5 groups of individuals with the highest exposure, mixtures are formed by pairs of pesticides with correlations above 0.7. Seven mixtures of 2–6 pesticides each were characterised. We identified the commodities that contributed the most to exposure. Pesticide mixtures can either be components of a single plant protection product applied together on the same crop or be from separate products that are consumed together during a meal. Of the 25 pesticides forming the mixtures, two—DDT and Dieldrin—are known persistent organic pollutants. The approach developed is generic and can be applied to all types of substances found in the diet in order to characterise the mixtures that should be studied first because of their adverse effects on health. [Copyright &y& Elsevier]

Abstract: Due to the broad spectrum of pesticide usages, consumers are exposed to mixtures of residues, which may have combined effects on human health. The PERICLES research program aims to test the potential combined effects of pesticide mixtures, which are likely to occur through dietary exposure. The co-exposure of the French general population to 79 pesticide residues present in the diet was first assessed. A Bayesian nonparametric model was then applied to define the main mixtures to which the French general population is simultaneously and most heavily exposed. Seven mixtures made of two to six pesticides were identified from the exposure assessment. An in vitro approach was used for investigating the toxicological effects of these mixtures and their corresponding individual compounds, using a panel of cellular models, i.e. primary rat and human hepatocytes, liver, intestine, kidney, colon and brain human cell lines. A set of cell functions and corresponding end-points were monitored such as cytotoxicity, real-time cell impedance, genotoxicity, oxidative stress, apoptosis and PXR nuclear receptor transactivation. The mixtures were tested in equimolar concentrations. Among the seven mixtures, two appeared highly cytotoxic, five activated PXR and depending on the assay one or two were genotoxic. In some experiments, the mixture effect was quantitatively different from the effect expected from the addition concept. The PERICLES program shows that, for the most pesticides mixtures to which the French general population is exposed, the toxic effects observed on human cells cannot be easily predicted based on the toxic potential of each compound. Consequently, additional studies should be carried on in order to more accurately define the mixtures of chemicals to which the consumers are exposed, as well as to improve the investigation, prediction and monitoring of their potential human health effects. [Copyright &y& Elsevier]

To assess human health risks related to the environment, it is necessary to aggregate exposure from multiple sources. The objective of this paper was to propose a relevant approach to combine data from heterogeneous populations and methodologies. Five different methods based on Monte-Carlo simulations were tested and compared. Differences were: taking into account or not stratification variable, timeline to assign exposure factors and concentration and way to account for concentration correlations. The methods were applied to estimate lead exposure from food, dust, soil, air, and tap water or French children aged between six months and three years old. Comparing results' uncertainty, it is recommended to 1) select a reference population representative of the target population, 2) select stratification variables to combine surveys, and 3) simulate a new population by randomly sampling individuals in the reference population and simultaneously assigning human exposure factors and environmental concentrations from other surveys in integrating correlations (MC1S). No difference was observed when taking into account correlations using vectors of determinist data from one survey or rank of correlations with the Iman-Conover method. Regardless the methods used to combine data, dust was the main exposure source, followed by soil and in a less extent by food. Exposures from air and tap water were found to be insignificant for most children., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: This paper deals with the dietary daily intakes of main polyunsaturated fatty acids (PUFA) in French children and adolescents., Methods: Dietary intakes of main PUFA were determined from a general French population of 1500 children (3-10 years) and adolescents (11-17 years) by using the most recent set of national robust data on food (National Survey INCA 2 performed in 2006 and 2007)., Results: Main results showed that mean daily intakes of total fat and n-6 PUFA linoleic acid (LA, 18:2n-6) were close to current recommended values for children and adolescent populations. However, 80% (children) to 90% (adolescents) of our French populations not only ingested low quantities of n-3 long-chain PUFA (docosahexaenoic (22:6n-3) and eicosapentaenoic (20:5n-3) acids) but also very low quantities of alpha-linolenic acid (ALA, 18:3n-3) at the origin of a non-balanced n-6/n-3 ratio. Inadequate consumption of EPA + DHA was also observed in subgroups of infants and adolescent who consumed more than two servings/week of fish., Conclusions: Such disequilibrium in PUFA dietary intakes in favor of n-6 PUFA could have adverse impact on cell membrane incorporation of long-chain n-3 PUFA and deleterious impacts on the health of children and adolescents. Promoting the consumption of both vegetable oils and margarines rich in ALA, and oily fish rich in long-chain n-3 PUFA might improve such PUFA disequilibrium.

Background: The French National survey INCA2 pointed out that the majority of the French population (children, adolescents, adults and elderly) ingest low quantities of n-3 polyunsaturated fatty acid (PUFA) in the form of both precursor (alpha-linolenic acid, ALA) and long-chain (mainly docosahexaenoic acid, DHA). However, we don't know whether such inadequate n-3 PUFA consumption is also found again in pregnant and lactating women., Methods: Dietary lipid and PUFA intakes were determined from 28 pregnant and 21 lactating French women by using the most recent set of national robust data on food (National Survey INCA2 performed in 2006 and 2007), and compared with that of 742 women of childbearing age., Results: Main results showed that mean daily intakes of n-3 PUFA were very low in this French woman population because no pregnant and lactating women met recommended dietary intakes (RDIs). Moreover, some of them ingested quantities 4 times (ALA) to 10 times (DHA) lower than RDIs. Very similar dietary intakes were observed in women of childbearing age., Conclusion: French pregnant and lactating women did not change their dietary habits to favor ALA and n-3 long-chain PUFA consumption via rich-ALA vegetable oils and fish and oily fish consumption, and have low n-3 PUFA dietary consumption typical of French women of childbearing age. Such PUFA intakes could have adverse impact on long-chain n-3 PUFA incorporation in brain membranes of fetus and infants, but also on cognitive and visual development of infants during the first years of life., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Quantity and quality of fatty acids (FA) in diet influence CVD risk. Consequently, health authorities promote recommended dietary intakes for FA, looking for optimal intakes in a primary prevention of CVD perspective. In parallel, a few data are available detailing intakes in national populations. The objective of the present study was to perform a large analysis combining the data of the French National Survey INCA 2 on food consumption performed in 2006 and 2007, and the nutritional content of food consumed in France updated in 2013 by the French Information Centre on Food Quality, to explore in details the FA intakes in French adults using the most recent available data. To compare the discrepancies in the observed intake levels with the French recommended levels, a weighted fat adherence score was built combining intakes of the different FA. Individual scores were computed in relation to official recommendations, and potential explanatory factors were identified. These data show that SFA intakes are persistently higher than national recommendations, combined with low intakes of MUFA and PUFA, particularly long-chain n-3 FA. Only 14·6 % of the French population met DHA intake recommendation, 7·8 % for EPA and 21·6 % for SFA. This situation remains unfavourable in terms of primary prevention of CVD. Consuming fish and other sources of n-3 FA, living in the south of France, being female, having a higher education level, and low alcohol consumption were associated with a healthier fat adherence score.

Within the food risk assessment procedure, the characterisation of the risk consists in the comparison of the dietary exposure with a health based guidance value established in a previous step. One of the identified weaknesses of this comparison is that the time is not considered in the description. The aim of this paper is to describe the dietary exposure as a dynamic process determined by the accumulation phenomenon due to successive dietary intakes and by the pharmacokinetics ruling the elimination process in between intakes. Such a process belong to the category of piecewise deterministic Markov processes, which are widely used in a large variety of applications in insurance risk or in operations research, ranging from queuing systems to inventory/storage models. The inputs of the Kinetic Dietary Exposure Model are the probability distributions governing intakes and inter-intake times, as well as the half-life of the contaminant in the human body. In this paper, an application to methyl mercury is considered, with exponential distributions for both the intakes and the inter-intake times, fitted from the French national consumption survey INCA, and a fixed half-life of 6 weeks for the elimination process. Within this framework, the process settles to a steady-state after approximately 5 years. A "Kinetic Tolerable Intake" (KTI), derived from the "Provisional Tolerable Weekly Intake" (PTWI) of 1.6 microg/kg bw, is set to 14.6 microg/kg and the probability of exceeding this threshold in the long run in the French adult female population is 1.22 E-15.

This article proposes statistical tools for quantitative evaluation of the risk due to the presence of some particular contaminants in food. We focus on the estimation of the probability of the exposure to exceed the so-called provisional tolerable weekly intake (PTWI), when both consumption data and contamination data are independently available. A Monte Carlo approximation of the plug-in estimator, which may be seen as an incomplete generalized U-statistic, is investigated. We obtain the asymptotic properties of this estimator and propose several confidence intervals, based on two estimators of the asymptotic variance: (i) a bootstrap type estimator and (ii) an approximate jackknife estimator relying on the Hoeffding decomposition of the original U-statistics. As an illustration, we present an evaluation of the exposure to Ochratoxin A in France.