Selecting mixtures on the basis of dietary exposure and hazard data: application to pesticide exposure in the European population in relation to steatosis

Abstract

33Populations are exposed to mixtures of pesticides through their diet on a daily basis. The 34 question of which substances should be assessed together remains a major challenge due to the 35 complexity of the mixtures. In addition, the associated risk is difficult to characterise. The 36EuroMix project (European Test and Risk Assessment Strategies for Mixtures) has developed 37 a strategy for mixture risk assessment. In particular, it has proposed a methodology that 38 combines exposures and hazard information to identify relevant mixtures of chemicals 39 belonging to any cumulative assessment group (CAG) to which the European population is 40 exposed via food. For the purposes of this study, food consumption and pesticide residue data 41 in food and drinking water were obtained from national surveys in nine European countries. 42Mixtures of pesticides were identified by a sparse non-negative matrix underestimation 43 (SNMU) applied to the specific liver steatosis effect in children from 11 to 15 years of age, and 44 in adults from 18 to 64 years of age in nine European countries. Exposures and mixtures of 144 45 pesticides were evaluated through four different scenarios: (1) chronic exposure with a merged 46 concentration dataset in the adult population, (2) chronic exposure with country-specific 47 concentration datasets in the adult population, (3) acute exposure with a merged concentration 48 dataset in the adult population, and (4) chronic exposure with a merged concentration dataset 49in the paediatric population. The relative potency factors of each substance were calculated to 50 2 express their potency relative to flusilazole, which was chosen as the reference compound. The 51 selection of mixtures and the evaluation of exposures for each country were carried out using 52 the Monte Carlo Risk Assessment (MCRA) software. 53Concerning chronic exposure, one mixture explained the largest proportion of the total variance 54 for each country, while in acute exposure, several mixtures were often involved. The results 55showed that there were 15 main pesticides in the mixtures, with a high contribution of imazalil 56 and dithiocarbamate. Since the concentrations provided by the different countries were merged 57 in the scenario using merged concentration data, differences between countries result from 58 differences in food consumption behaviours. These results support the approach that using 59 merged concentration data to estimate exposures in Europe seems to be realistic, as foods are 60 traded across European borders. The originality of the proposed approach was to start from a 61 CAG and to integrate information from combined exposures to identify a refined list of mixtures 62 with fewer components. As this approach was sensitive to the input data and required significant 63 resources, efforts should continue regarding data collection and harmonisation among the 64 different aspects within the pesticides regulatory framework, and to develop methods to group 65 substances and mixtures to characterise the r...

Cumulative dietary exposure assessment of pesticides that have acute effects on the nervous system using MCRA software

“…In accordance with Article 36 of Regulation (EC) No 178/2002, this task has been carried out exclusively by the authors in the context of a grant agreement between the European Food Safety Authority and the authors. In the EU-funded project EuroMix (Grant Agreement Number 633172) 10 useful tools have been surveyed, developed and/or implemented in the MCRA software, such as the Maximum Cumulative Ratio (MCR) method and the SNMU method, to diagnose mixtures of concern and the persons exposed to multiple pesticides (Crépet, 2019). It cannot be considered as an output adopted by the Authority.…”

“…Consequently, it is relevant to distinguish between exposures of persons that are exposed to multiple pesticides as listed in Table 14: and the persons that are exposed to one pesticide with a high residue concentration as shown in Table 15: . In the EU-funded project EuroMix (Grant Agreement Number 633172) 10 useful tools have been surveyed, developed and/or implemented in the MCRA software, such as the Maximum Cumulative Ratio (MCR) method and the SNMU method, to diagnose mixtures of concern and the persons exposed to multiple pesticides (Crépet, 2019 The present document has been produced and adopted by the bodies identified above as authors. In accordance with Article 36 of Regulation (EC) No 178/2002, this task has been carried out exclusively by the authors in the context of a grant agreement between the European Food Safety Authority and the authors.…”

Combined effects of maternal exposure to fungicides on behavioral development in F1‐generation mice: 2. Fixed‐dose study of thiabendazole

“…They suggest that these pesticides would need a high control as well as a refinement of the risk assessment to ensure their safety for the population. IMZ contributes one of the most to the European pesticide mixture exposure from national surveys in nine European countries (Crépet et al, 2019).…”

Potential impact of prioritisation methods on the outcome of cumulative exposure assessments of pesticides

“…According to EFSA, it is likely that even within large AGs the cumulative exposure is mainly driven by a few substances. Indeed, CRA performed for AGs based on phenomenological effect showed that cumulative exposure could be driven by only a few substances (EFSA, 2020a;Crépet et al, 2019). Therefore, EFSA proposed a prioritisation system based as described in section 1.1 and displayed in Figure 1: .…”

“…Annex A presents an overview hazard metrics of specific effects (van Klaveren et al, 2019(van Klaveren et al, , 2019b and critical effects (OpenFoodTox database complemented with EU pesticide database)…”