Epidemiological and toxicological evidence suggests that PFOA and PFOS elicit a decrease in BrthW both in humans and rodents. However, the effective animal extrapolated serum concentrations are 10-10 times higher than those in humans. Thus, there is no quantitative toxicological evidence to support the epidemiological association, thus reducing the biological plausibility of a causal relationship.

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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...