Surveillance des expositions alimentaires aux résidus de pesticides : développement d’une méthode globale d’appréciation quantitative du risque pour optimiser l’évaluation et la gestion du risque sanitaire

L'évaluation des produits phytopharmaceutiques, leur mise sur le marché et la surveillance des résidus de pesticides dans les aliments sont harmonisés au niveau européen. Les estimations des expositions alimentaires a posteriori réalisées en Europe sont cependant incomplètes au regard du nombre de denrées et de pesticides évalués, et les données de consommation utilisées sont souvent anciennes. L’amélioration des connaissances sur les risques alimentaires liés aux pesticides constitue l’un des enjeux majeurs de santé publique. L’objectif de cette thèse est de construire un système national de surveillance a posteriori des expositions et des risques alimentaires afin de guider (1) d’une part les gestionnaires du risque dans le cadre de l’élaboration de leurs programmes de surveillance et des mesures préventives et correctives ; (2) d’autre part les évaluateurs du risque dans l’orientation des travaux de recherche et d’expertise en métrologie, expologie et toxicologie. Ce système de surveillance comprend deux outils complémentaires : (1) une méthode d’appréciation quantitative du risque dite « globale » basée sur quatre indicateurs chroniques et aigus actualisés annuellement à partir des résultats des derniers plans de surveillance et des limites maximales de résidus ; (2) des études pluriannuelles dites études de l’alimentation totale (EAT) dont la première EAT française sur les pesticides. Ces deux approches sont basées sur les données de l’étude individuelle et nationale des consommations alimentaires Inca 2 de l’Anses. La méthode globale annuelle intègre une échelle de priorités ayant permis de hiérarchiser les risques pour 519 pesticides. Les niveaux d’exposition estimés dans l’EAT2 sont globalement plus réalistes que ceux issus de la méthode annuelle. Cependant, les deux outils n’ont pas permis initialement d’affiner suffisamment l’évaluation pour certains pesticides. Par conséquent, la méthode a été ajustée afin de mieux gérer les résultats d’analyse censurés. Après ajustement, 14% des pesticides sont identifiés comme prioritaires en termes d’évaluation et/ou de gestion du risque (niveaux 2 à 6), compte tenu de dépassements des valeurs toxicologiques de référence. A partir des couples prioritaires pesticide/denrée, un plan d’échantillonnage est défini pour les prochains plans de surveillance. Des mesures de gestion correctives et une intensification des contrôles à la production et à la distribution sont recommandés pour 11 pesticides de niveau de risque maximal (niveau 6) en lien avec 16 couples pesticide/denrée. Au final, ce système national est plus complet et plus adapté à la population française que l’évaluation communautaire annuelle. Les résultats obtenus sont par ailleurs cohérents avec ceux de la première étude nationale de biosurveillance sur les pesticides. Enfin, la méthode globale annuelle intégrera les évolutions méthodologiques communautaires récentes pour l’évaluation des risques cumulés. ABSTRACT : The evaluation of plant protection products, their marketing and the monitoring of pesticide residues in food are harmonized in the European Union. Nevertheless, the assessment of dietary exposure at post-regulation level is incomplete due to the small number of foods and pesticides taken into account. In addition, consumption data are often obsolete. Improving knowledge on the dietary risk of pesticide residues is one of the major challenges to public health. The aim of this thesis is to build a national system for the ex post monitoring of dietary exposure and risk to the general population in order to guide (1) risk managers in the development of their monitoring programmes and preventive and corrective measures; (2) risk assessors in guiding research and expertise in metrology, exposure assessment and toxicology. This monitoring system includes two complementary tools: (1) an annual method of quantitative risk assessment based on four chronic and acute indicators updated each year and based on the results of the latest monitoring plans and maximum residue levels; (2) multi-year total diet studies (TDS), including the first TDS on pesticide residues (TDS2). These two approaches are based on the results of ANSES’s INCA2 individual and national consumption survey. This annual method includes a 6-level risk scale that enables the prioritization of risk for 519 pesticides. The exposure levels estimated in TDS2 are in general more realistic than those of the annual method. However, for certain pesticides it was not possible to sufficiently refine exposure levels using these two tools. Consequently, the annual method was adjusted to improve management of left-censored analytical results. After adjustment, 14% of pesticides were identified as a priority in terms of risk assessment and/or risk management (levels 2 to 6), given that they exceeded the toxicological reference values. Based on priority pesticide/foodstuff pairs, a sampling plan has been established for subsequent monitoring programmes. Corrective management measures and intensified controls of production and distribution are recommended for 11 pesticides scored at maximal risk level (level 6) in association with 16 pesticide/foodstuff pairs. In the end, this national system is more comprehensive and better suited to the French population than the annual EU assessment. The results are also consistent with those of the first national biomonitoring study on pesticides. The annual method will also incorporate recent European methodological developments for cumulative risk assessment

Dietary exposure to pesticide residues and associated health risks in infants and young children – Results of the French infant total diet study

A total diet study (TDS) was undertaken to estimate the chronic dietary exposure to pesticide residues and health risks for the French infants and young children below 3 years old. As a whole, 516 pesticides and metabolites were analysed in 309 food composite samples including 219 manufactured baby foods and 90 common foods, which cover 97% of infants and young children's diet. These composite samples were prepared using 5,484 food products purchased during all seasons from 2011 to 2012 and processed as consumed. Pesticide residues were detected in 67% of the samples and quantified in 27% of the baby food samples and in 60% of the common foods. Seventy-eight different pesticides were detected and 37 of these quantified at levels ranging from 0.02 to 594 µg/kg. The most frequently detected pesticides (greater than 5% samples) were (1) the fungicides 2-phenylphenol, azoxystrobin, boscalid, captan and its metabolite tetrahydrophthalimide, carbendazim, cyprodinil, difenoconazole, dodine, imazalil, metalaxyl, tebuconazole, thiabendazole, (2) the insecticides acetamiprid, pirimiphos-methyl and thiacloprid, (3) the herbicide metribuzin and (4) the synergist piperonyl butoxide. Dietary intakes were estimated for each of the 705 individuals studied and for 431 pesticides incl. 281 with a toxicological reference value (TRV). In the lower-bound scenario, which tends to underestimate the exposure, the TRV were never exceeded. In the upper-bound scenario that overestimates exposure, the estimated intakes exceeded the TRV for dieldrin and lindane (two persistent organic pollutants) and propylene thiourea, a metabolite of propineb. For these three substances, more sensitive analyses are needed to refine the assessment. For 17 other detected and/or prioritised pesticides, the risk could not be characterised due to the lack of a valid TRV, of certain food analyses or the absence of analytical standards for their metabolites. Keywords: Food safety, Infants and young children, Pesticide residues, Total diet study, Exposure assessment, Risk characterizatio

Monitoring of dietary exposure to pesticide residues : development of a method of quantitative risk assessment to optimize the evaluation and management of health risks

L'évaluation des produits phytopharmaceutiques, leur mise sur le marché et la surveillance des résidus de pesticides dans les aliments sont harmonisés au niveau européen. Les estimations des expositions alimentaires a posteriori réalisées en Europe sont cependant incomplètes au regard du nombre de denrées et de pesticides évalués, et les données de consommation utilisées sont souvent anciennes. L’amélioration des connaissances sur les risques alimentaires liés aux pesticides constitue l’un des enjeux majeurs de santé publique. L’objectif de cette thèse est de construire un système national de surveillance a posteriori des expositions et des risques alimentaires afin de guider (1) d’une part les gestionnaires du risque dans le cadre de l’élaboration de leurs programmes de surveillance et des mesures préventives et correctives ; (2) d’autre part les évaluateurs du risque dans l’orientation des travaux de recherche et d’expertise en métrologie, expologie et toxicologie. Ce système de surveillance comprend deux outils complémentaires : (1) une méthode d’appréciation quantitative du risque dite « globale » basée sur quatre indicateurs chroniques et aigus actualisés annuellement à partir des résultats des derniers plans de surveillance et des limites maximales de résidus ; (2) des études pluriannuelles dites études de l’alimentation totale (EAT) dont la première EAT française sur les pesticides. Ces deux approches sont basées sur les données de l’étude individuelle et nationale des consommations alimentaires Inca 2 de l’Anses. La méthode globale annuelle intègre une échelle de priorités ayant permis de hiérarchiser les risques pour 519 pesticides. Les niveaux d’exposition estimés dans l’EAT2 sont globalement plus réalistes que ceux issus de la méthode annuelle. Cependant, les deux outils n’ont pas permis initialement d’affiner suffisamment l’évaluation pour certains pesticides. Par conséquent, la méthode a été ajustée afin de mieux gérer les résultats d’analyse censurés. Après ajustement, 14% des pesticides sont identifiés comme prioritaires en termes d’évaluation et/ou de gestion du risque (niveaux 2 à 6), compte tenu de dépassements des valeurs toxicologiques de référence. A partir des couples prioritaires pesticide/denrée, un plan d’échantillonnage est défini pour les prochains plans de surveillance. Des mesures de gestion correctives et une intensification des contrôles à la production et à la distribution sont recommandés pour 11 pesticides de niveau de risque maximal (niveau 6) en lien avec 16 couples pesticide/denrée. Au final, ce système national est plus complet et plus adapté à la population française que l’évaluation communautaire annuelle. Les résultats obtenus sont par ailleurs cohérents avec ceux de la première étude nationale de biosurveillance sur les pesticides. Enfin, la méthode globale annuelle intégrera les évolutions méthodologiques communautaires récentes pour l’évaluation des risques cumulés.The evaluation of plant protection products, their marketing and the monitoring of pesticide residues in food are harmonized in the European Union. Nevertheless, the assessment of dietary exposure at post-regulation level is incomplete due to the small number of foods and pesticides taken into account. In addition, consumption data are often obsolete. Improving knowledge on the dietary risk of pesticide residues is one of the major challenges to public health. The aim of this thesis is to build a national system for the ex post monitoring of dietary exposure and risk to the general population in order to guide (1) risk managers in the development of their monitoring programmes and preventive and corrective measures; (2) risk assessors in guiding research and expertise in metrology, exposure assessment and toxicology. This monitoring system includes two complementary tools: (1) an annual method of quantitative risk assessment based on four chronic and acute indicators updated each year and based on the results of the latest monitoring plans and maximum residue levels; (2) multi-year total diet studies (TDS), including the first TDS on pesticide residues (TDS2). These two approaches are based on the results of ANSES’s INCA2 individual and national consumption survey. This annual method includes a 6-level risk scale that enables the prioritization of risk for 519 pesticides. The exposure levels estimated in TDS2 are in general more realistic than those of the annual method. However, for certain pesticides it was not possible to sufficiently refine exposure levels using these two tools. Consequently, the annual method was adjusted to improve management of left-censored analytical results. After adjustment, 14% of pesticides were identified as a priority in terms of risk assessment and/or risk management (levels 2 to 6), given that they exceeded the toxicological reference values. Based on priority pesticide/foodstuff pairs, a sampling plan has been established for subsequent monitoring programmes. Corrective management measures and intensified controls of production and distribution are recommended for 11 pesticides scored at maximal risk level (level 6) in association with 16 pesticide/foodstuff pairs. In the end, this national system is more comprehensive and better suited to the French population than the annual EU assessment. The results are also consistent with those of the first national biomonitoring study on pesticides. The annual method will also incorporate recent European methodological developments for cumulative risk assessment

Exposure to pesticide residues and contaminants of the vegetarian population—French data

In the present chapter, dietary exposures of different vegetarian populations to pesticide residues as well as those to contaminants are discussed, based on French data. For 48 pesticide residues out of 421, it was shown that, based on theoretical calculation of the exposure, vegetarians could have higher exposures than those of the general population, the pescetarian population being very close to the situation observed for the general population. On the other hand, biomonitoring studies demonstrated that there was a trend toward lower organochlorine contamination in the vegan population compared to that of the general population. With regard to contaminants, exposures to phytoestrogens or to some trace elements (Cd, Al, Ni) were higher for the vegetarian population compared to those of the general population. Otherwise, the vegetarian population studied in the present study was less exposed than the general population to other contaminants such as some persistent organic pollutants, some mycotoxins, and some trace elements

Multiple pesticide analysis in hair samples of pregnant French women Results from the ELFE national birth cohort

International audienceBackground - A growing body of evidence suggests that prenatal exposure to pesticides might impair fetal development. Nonetheless, knowledge about pesticide exposure of pregnant women, especially in Europe, is largely restricted to a limited panel of molecules. Aim - To characterize the concentration of 140 pesticides and metabolites in hair strands from women in the ELFE French nationwide birth cohort. Methods - Among cohort members who gave birth in northeastern and southwestern France in 2011, we selected those with a sufficient available mass of hair (n = 311). Bundles of hair 9 cm long were collected at delivery. We screened 111 pesticides and 29 metabolites, including 112 selected a priori based on their reported usage or detection in the French environment. The bundles of hair from 47 women were split into three segments to explore the intraindividual variability of the exposure. Intraclass correlation coefficients (ICCs) were computed for the chemicals with a detection frequency >70%. Results - We detected a median of 43 chemicals per woman (IQR 38-47). Overall, 122 chemicals (>20 chemical families) were detected at least once, including 28 chemicals detected in 70-100% of hair samples. The highest median concentrations were observed for permethrin (median: 37.9 pg/mg of hair), p-nitrophenol (13.2 pg/mg), and pentachlorophenol (10.0 pg/mg). The ICCs for the 28 chemicals studied ranged from 0.59 to 0.94. Conclusion - Pregnant women are exposed to multiple pesticides simultaneously from various chemical families, including chemicals suspected to be reproductive toxicants or endocrine disruptors. The ICCs suggest that the intraindividual variability of pesticide concentrations in hair is lower than its interindividual variability

Chronic dietary exposure to pesticide residues and associated risk in the French ELFE cohort of pregnant women

International audienceDietary exposure to pesticide residues may present a risk to public health, especially for sensitive populations such as pregnant women. To characterize this risk, this study assessed chronic dietary exposure to pesticide residues based on the French ELFE cohort. A self-administered food frequency questionnaire (FFQ) about the last three months of pregnancy filled in by pregnant women in 2011 was used in combination with occurrence data from French Total Diet Studies completed by the results of national monitoring programs on pesticide residues in food. The dietary intake of pesticides (μg/kg of body weight/day) was estimated for 14,099 pregnant women with a complete FFQ, for 317 substances under two occurrence scenarios to handle left-censored data: a lower-bound scenario (LB), where undetected results were set to zero, and an upper-bound scenario (UB), where undetected results were set to the detection limit if the substance was expected to be found in food and zero if it was not. The risk was assessed for 284 substances with a toxicological reference value (TRV) and a good coverage level of the diet potentially contributing to pesticide intake. The cumulative risk was also assessed for seven effects on nervous and thyroid systems using the hazard index and the Cumulative Assessment Groups defined by EFSA. Substances with the highest exposure levels under the LB scenario were, in decreasing order, imazalil, piperonyl butoxide, chlorpropham, thiabendazole, iprodione and propargite. Under the LB scenario, only for lindane did women have a statistically significant probability of exceeding the TRV (2.4%). Under the UB scenario, risk could not be excluded for nine other substances. A better management of left-censored data and more sensitive analyses of the main food contributors might help to refine the UB exposure and risk assessments. A statistically significant cumulative risk was found for neurochemical effects related to high intake levels of three organophosphate insecticides (chlorpyrifos, pirimiphos-methyl and dimethoate) mainly detected in fruits and cereal