Prenatal exposure to pesticides and risk of preeclampsia among pregnant women: Results from the ELFE cohort.

BACKGROUND: Preeclampsia is a pregnancy-specific syndrome caused by abnormal placentation. Although environmental chemicals, including some pesticides, are suspected of impairing placentation and promoting preeclampsia, its relationship with preeclampsia has been insufficiently explored. OBJECTIVES: We aimed to investigate the relation between non-occupational exposure to pesticides during pregnancy and the risk of preeclampsia. METHODS: The study cohort comprised 195 women with and 17,181 without preeclampsia from the ELFE birth cohort. We used toxicogenomic approaches to select 41 pesticides of interest for their possible influence on preeclampsia. We assessed household pesticide use (self-reported data), environmental exposure to agricultural pesticides (geographic information systems), and dietary exposure (food-frequency questionnaire with data from monitoring pesticide residues in food and water). Dietary exposures to pesticides were grouped into clusters of similar exposures to resolve collinearity issues. For each exposure source, pesticides were mutually adjusted, and odds ratios estimated with logistic regression models. RESULTS: The quantity of prochloraz applied within a kilometer of the women's homes was higher in women with than without preeclampsia (fourth quartile vs. others; adjusted odds ratio [aOR] = 1.54; 95%CI: 1.02, 2.35), especially when preeclampsia was diagnosed before 34 weeks of gestation (aOR = 2.25; 95%CI: 1.01, 5.06). The reverse was observed with nearby cypermethrin application (aOR = 0.59, 95%CI: 0.36, 0.96). In sensitivity analyses, women with preeclampsia receiving antihypertensive treatment had a significantly higher probability of using herbicides at home during pregnancy than women without preeclampsia (aOR = 2.20; 95%CI: 1.23, 3.93). No statistically significant association was found between dietary exposure to pesticide residues and preeclampsia. DISCUSSION: While the most of the associations examined remained statistically non-significant, our results suggest the possible influence on preeclampsia of residential exposures to prochloraz and some herbicides. These estimations are supported by toxicological and mechanistic data.

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.

Relevance of integrating agricultural practices in pesticide dietary intake indicator.

The aim of this study is to develop a new indicator of pesticide dietary intake to screen pesticides to include in monitoring programs. This new indicator called the adjusted TMDI (TMDI_Ad), taking account actual pesticide agricultural uses in France, is more precise than the theoretical maximum dietary intake (TMDI), based on maximum residue levels (MRLs) that is usually used. This new modeling of dietary intake is refined according to actual agricultural pesticide uses on 44 raw agricultural commodities (RAC), among the most consumed in France, and the rate of food importation of these RAC. The TMDI_Ad was below the TMDI for 322 pesticides (79%). The TMDI was above the ADI, for 46 substances. Although 43 of them had a TMDI_Ad below the TMDI, still 36 had a TMDI_Ad above the ADI, which corresponded to substances with the lowest ADIs. Overall, these results indicate that the TMDI_Ad is a useful tool to plan monitoring programs and to refine dietary exposure, according to actual pesticide uses. However, for very toxic substances, having a very low ADI, such as unauthorized substances, other studies have to be conducted in order to better estimate consumer dietary intakes.

Validation and application of analytical method for glyphosate and glufosinate in foods by liquid chromatography-tandem mass spectrometry.

A reliable and sensitive method was developed for simultaneous determination of glyphosate and glufosinate in various food products by liquid chromatography-tandem mass spectrometry. Based on extraction, derivatization with 9-fluorenylmethylchloroformate and purification on solid phase extraction column, quantification was done by using isotopic-labeled analytes as internal standard and calibration in matrix. Good selectivity and sensitivity were achieved with a limit of quantification of 5 µg/kg. The recoveries of these two pesticides ranged from 91% to 114% with inter-day and relative standard deviation of 3.8-6.1% in five matrices of cereal group spiked at 5, 10, and 20 µg/kg. An accuracy profile was performed for method validation, demonstrating the accuracy and precision of the method for the studied food groups. The verification results in expanded food groups indicated extensive applicability for the analysis of glyphosate and glufosinate. Finally, the developed method was applied to analyze 136 food samples including milk-based baby foods from the French Agency for Food, Environmental and Occupational Health & Safety. Glyphosate residues were detected in two breakfast cereal samples (6.0 and 34 µg/kg). Glufosinate residues were found in a sample of boiled potatoes (9.8 µg/kg). No residues were detected in the other samples, including milk-based baby foods with limits of detection ranging from 1 to 2 µg/kg. The method has been applied for routine national monitoring of glyphosate and glufosinate in various foods.

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

BACKGROUND: 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.

Use of EFSA Pesticide Residue Intake Model (EFSA PRIMo revision 3).

Since 2007, the EFSA PRIMo (Pesticide Residue Intake Model), an Excel-based calculation spreadsheet, is the standard tool used at EU level to perform the dietary risk assessment for pesticide residues in the framework of setting and reviewing of maximum residue levels for pesticides under Regulation (EC) No 396/2005 and in the peer review of pesticides under Regulation (EU) No 1107/2009. The model was now updated with regard to food consumption data derived from some recent dietary food surveys. In addition, new functionalities were included in the calculation spread sheet to make the tool more user-friendly and to allow automatic integration of the EFSA PRIMo in the workflows where dietary risk assessments are performed.

Setting of a maximum residue level for cyantraniliprole in leeks.

In accordance with Article 53 of Regulation (EC) 1107/2009, the United Kingdom granted a 120-day emergency authorisation for the use of cyantraniliprole in leek. In order to accommodate for the new use, the Agriculture & Horticulture Development Board submitted an application to raise the existing maximum residue level (MRL) for the crop concerned. The United Kingdom, as evaluating Member State, summarised the data provided by the applicant in an evaluation report which was submitted to the European Commission and forwarded to EFSA. Sufficient residue trials are available to derive an MRL proposal of 0.6 mg/kg for leeks in accordance with the emergency authorised good agricultural practice (GAP). Adequate analytical methods for enforcement are available to control the residues of cyantraniliprole in the commodities under consideration. Based on the risk assessment results, EFSA concluded that intake of residues resulting from the use of cyantraniliprole according to the reported agricultural practice is unlikely to present a risk to consumer health.

Modification of the existing maximum residue level for metazachlor in Chinese cabbage.

In accordance with Article 6 of Regulation (EC) No 396/2005, the evaluating Member State (EMS), France, received an application from BASF SE to modify the existing maximum residue level (MRL) for the active substance metazachlor in Chinese cabbage. To accommodate for the intended use of metazachlor, France proposed to raise the existing MRL from the value of 0.2 mg/kg to 0.6 mg/kg. France drafted an evaluation report in accordance with Article 8 of Regulation (EC) No 396/2005, which was submitted to the European Commission and forwarded to EFSA. According to EFSA, the data are sufficient to derive a MRL proposal of 0.6 mg/kg for the proposed use on Chinese cabbage. Adequate analytical enforcement methods are available to control the residues of metazachlor on the commodity under consideration. Based on the risk assessment results, EFSA concludes that the proposed use of metazachlor on Chinese cabbage will not result in a consumer exposure exceeding the toxicological reference values and therefore is unlikely to pose a consumer health risk.

Setting of import tolerances for flubendiamide in apricots, peaches, nectarines, plums and soya beans.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Bayer CropScience AG submitted a request to the competent national authority in Greece to set import tolerances for the active substance flubendiamide in apricots, peaches, nectarines, plums and soya beans. The data submitted in support of the request were found to be sufficient to derive maximum residue level (MRL) proposals for apricots, peaches/nectarines, plums. For soya beans, further risk management considerations are required to decide the import tolerance to be set. Adequate analytical methods for enforcement are available to control the residues of flubendiamide in plant matrices. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the use of flubendiamide according to the reported agricultural practices is unlikely to present a risk to consumer health.

Modification of the existing maximum residue level for fluopicolide in chards.

In accordance with Article 6 of Regulation (EC) No 396/2005, the competent national authority in Belgium sent an application to modify the existing maximum residue level (MRL) for the active substance fluopicolide in chards. In order to accommodate for the intended use of fluopicolide, the evaluating Member State (EMS) proposed to raise the existing MRLs from 4 mg/kg to 6 mg/kg. Belgium drafted the evaluation report in accordance with Article 8 of Regulation (EC) No 396/2005, which was submitted to the European Commission and forwarded to EFSA. According to EFSA, the data are sufficient to derive a MRL proposal of 6 mg/kg on chards. Adequate analytical enforcement methods are available to control the residues of fluopicolide in chards at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the proposed use of fluopicolide on chards will not result in a consumer exposure exceeding the toxicological reference values and therefore is unlikely to pose a consumer health risk.

Review of the existing maximum residue levels for bispyribac according to Article 12 of Regulation (EC) No 396/2005.

According to Article 12 of Regulation (EC) No 396/2005, EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substance bispyribac. To assess the occurrence of bispyribac residues in plants, processed commodities, rotational crops and livestock, EFSA considered the conclusions derived in the framework of Directive 91/414/EEC as well as the European authorisations reported by Member States (including the supporting residues data). Based on the assessment of the available data, MRL proposals were derived and a consumer risk assessment was carried out. All information required by the regulatory framework was present and a risk to consumers was not identified.

Review of the existing maximum residue levels for flurochloridone according to Article 12 of Regulation (EC) No 396/2005.

According to Article 12 of Regulation (EC) No 396/2005, EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substance flurochloridone. To assess the occurrence of flurochloridone residues in plants, processed commodities, rotational crops and livestock, EFSA considered the conclusions derived in the framework of Commission Regulation (EC) No 33/2008 as well as the European authorisations reported by Member States (including the supporting residues data). Based on the assessment of the available data, MRL proposals were derived and a consumer risk assessment was carried out. Although no apparent risk to consumers was identified, some information required by the regulatory framework was missing. Hence, the consumer risk assessment is considered indicative only and some MRL proposals derived by EFSA still require further consideration by risk managers.

Modification of the existing maximum residue levels for mandestrobin in apricots, cherries, peaches/nectarines and plums.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Sumitomo Chemical Agro Europe S.A.S. submitted a request to the competent national authority in France, to modify the existing maximum residue levels (MRL) for the active substance mandestrobin in apricots, cherries, peaches/nectarines and plums. The data submitted in support of the request were found to be sufficient to derive MRL proposals for apricots, cherries, peaches/nectarines and plums. Adequate analytical methods for enforcement are available to control the residues of mandestrobin in the commodities under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. A short-term dietary risk assessment was not required. Based on the long-term risk assessment results, EFSA concluded that the long-term intake of residues resulting from the use of mandestrobin according to the agricultural practices reported in the good agricultural practice (GAP) for applications at growth stages BBCH 77-87 is unlikely to present a risk to consumer health. The GAP for applications at growth stages BBCH 57-69 is not adequately supported by residue trials data. The reliable end points appropriate for use in regulatory risk assessment are presented.

Modification of the existing maximum residue levels for clopyralid in spring/green/Welsh onions and leeks.

In accordance with Article 6 of Regulation (EC) No 396/2005, the Agriculture and Horticulture Development Board (AHDB) submitted a request to the competent national authority in the United Kingdom, to modify the existing maximum residue levels (MRL) for the active substance clopyralid in spring onions and leeks. The data submitted in support of the request were found to be sufficient to derive MRL proposals for spring onions/green onions and Welsh onions and for leeks based on the residue definition for enforcement in Regulation (EC) No 396/2005. An adequate analytical method for enforcement is available to control the residues on the commodities under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the available information, EFSA concluded that the long-term intake of residues resulting from the use of clopyralid according to the reported agricultural practices is unlikely to present a risk to consumer health. The reliable end points, appropriate for use in regulatory risk assessment, are presented.

Modification of the existing maximum residue level for deltamethrin in kale.

In accordance with Article 6 of Regulation (EC) No 396/2005, the Agriculture and Horticulture Development Board (AHDB) submitted a request to the competent authority in the United Kingdom (evaluating Member State (EMS)) to modify the existing maximum residue level (MRL) for the active substance deltamethrin in kale. To accommodate for the intended use of deltamethrin, it was considered necessary to raise the existing MRL. Based on the evaluation report prepared by the EMS in accordance with Article 8 of Regulation (EC) No 396/2005, EFSA concludes that the applicant provided sufficient data to derive an MRL proposal of 0.15 mg/kg for the proposed uses in kale. Adequate analytical enforcement methods are available to control compliance with the proposed MRL for deltamethrin in kale. In a tentative risk assessment, no consumer concern has been identified; however, the risk assessment was affected by non-standard uncertainties. Further risk management considerations are required to decide whether the MRL proposal is acceptable.

Modification of the existing maximum residue levels for trifloxystrobin in various crops.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Bayer CropScience submitted a request to the competent national authority in the Netherlands to modify the existing maximum residue levels (MRL) for the active substance trifloxystrobin in small fruits and berries (whole group), lettuce and salad plants (whole group), purslanes, beans (without pods) and peas (with and without pods) and pulses. The data submitted in support of the request were found to be sufficient to derive MRL proposals for all crops under consideration. Adequate analytical methods for enforcement are available to control the residues of trifloxystrobin on the commodities under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg and in animal matrices at the validated LOQ of 0.01 mg/kg. The risk assessment included a preliminary assessment considering the acute reference dose proposed during the peer review. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the use of trifloxystrobin according to the reported agricultural practices is unlikely to present a risk to consumer health, except for escaroles. For escaroles, based on the recently proposed acute reference dose, EFSA concluded that a risk from short-term intake cannot be excluded. Therefore, no MRL has been proposed for this use.

Review of the existing maximum residue levels for fenoxycarb according to Article 12 of Regulation (EC) No 396/2005.

According to Article 12 of Regulation (EC) No 396/2005, EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substance fenoxycarb. To assess the occurrence of fenoxycarb residues in plants, processed commodities, rotational crops and livestock, EFSA considered the conclusions derived in the framework of Directive 91/414/EEC as well as the European authorisations reported by Member States (including the supporting residues data). Based on the assessment of the available data, MRL proposals were derived and a consumer risk assessment was carried out. Although no apparent risk to consumers was identified, some information required by the regulatory framework was missing. Hence, the consumer risk assessment is considered indicative only and some MRL proposals derived by EFSA still require further consideration by risk managers.

Modification of the existing maximum residue levels for fenhexamid in various crops.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Bayer CropScience SAS submitted a request to the competent national authority in Italy to modify the existing maximum residue levels (MRL) for the active substance fenhexamid in plums, blueberries, cranberries, currants, gooseberries and beans with pods. The data submitted in support of the request were found to be sufficient to derive MRL proposals for all crops under consideration. Adequate analytical methods for enforcement are available to control the residues of fenhexamid in plant matrices. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the use of fenhexamid according to the reported agricultural practices is unlikely to present a risk to consumer health.

Modification of the existing maximum residue level for pyrimethanil in cucurbits with edible peel.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Arysta LifeScience Benelux SPRL submitted a request to the competent national authority in Italy, to modify the existing maximum residue level (MRL) for the active substance pyrimethanil in cucurbits with edible peel. The data submitted in support of the request were found to be sufficient to derive a MRL proposal for cucurbits with edible peel. Adequate analytical methods for enforcement are available to control the residues of pyrimethanil on the commodities under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the use of pyrimethanil according to the reported agricultural practice is unlikely to present a risk to consumer health.

Modification of the existing maximum residue levels for fosetyl-Al in tree nuts, pome fruit, peach and potato.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicants Bayer CropScience Europe and Oxon Italia S.p.A. submitted requests to the competent national authority in Spain and Italy, respectively, to modify the existing maximum residue levels (MRLs) for fosetyl in peach and potato from the intended southern Europe (SEU) uses of fosetyl-Al. The applicants Adama Agriculture B.V., Fitosanitarios Bajo Riesgo AIE and Almond Board of California submitted each an application to the competent national authority in France to modify the MRLs for fosetyl-Al in pome fruits, peaches and tree nuts (except coconut) for the intended/authorised uses of the active substance potassium phosphonates. The data submitted in support of the requests were found to be sufficient to derive MRL proposals for all the crops under consideration. Adequate analytical methods for enforcement are available to control the residues of fosetyl-Al and phosphonic acid in plant matrices under consideration. EFSA concluded that the proposed use of fosetyl-Al on potatoes and the proposed uses of potassium phosphonates on pome fruits and peaches and the authorised use of potassium phosphonates on tree nuts in the United States are unlikely to result in a consumer exposure exceeding the toxicological reference values for phosphonic acid and fosetyl and therefore are unlikely to pose a risk to consumers' health. However, the risk assessment is considered to be tentative and has to be updated as soon as the approval of the renewal of fosetyl and the review of existing uses of potassium phosphonates and disodium phosphonate is finalised.