La prima parte dell’elaborato presenta le origini e lo sviluppo delle politiche di valutazione del rischio per le sostanze chimiche. Dopo un primo inquadramento storico, l’attenzione è stata dedicata a temi emergenti come la valutazione delle incertezze, la necessità di integrazione delle valutazioni del rischio per l’uomo e per l'ambiente. La seconda parte presenta l’evoluzione delle politiche di valutazione del rischio dei prodotti fitosanitari, soprattutto a livello europeo (dall’applicazione della direttiva 91/414 all’attuale regolamento 1107/2009), con particolare attenzione all’applicazione del principio di precauzione. Il terzo capitolo approfondisce le fasi e gli approcci delle attuali procedure di valutazione ambientale del rischio dei pesticidi usati a livello europeo e americano; è stato in particolar modo esplorato il tema dell’individuazione degli obiettivi specifici di protezione in fase preliminare di valutazione del rischio. Il quarto capitolo tratta di un tema attualmente molto dibattuto, ovvero la valutazione dei potenziali effetti combinati sugli organismi non bersaglio esposti a più sostanze attive simultaneamente. Infine, l’obiettivo del quinto capitolo è quello di valutare la contaminazione ambientale dovuta all’applicazione di fungicidi a base rame su melo. A tale scopo è stato testato un nuovo modello per il calcolo integrato dell’esposizioni umana e ambientale MERLIN – Expo, sviluppato grazie al progetto europeo 4FUN. I risultati ottenuti per le acque superficiali e il sedimento sono stati confrontati con i risultati degli attuali modelli usati in Unione Europea, i modelli FOCUS. Le simulazioni probabilistiche hanno anche permesso di effettuare valutazioni di incertezza e sensitività sui parametri utilizzati nelle simulazioni. / This PhD thesis is a multidisciplinary work on the risk assessment of plant protection products including both legislative and scientific aspects. The first part of the thesis introduces the origin of risk assessment procedures with a wide glance on the whole process of risk analysis to protect the humans and the environment. The accent is put on emerging issues and trends, such as the uncertainties appraisal, the necessity of integration between human and environmental impacts without ignoring socio- economic and behavioural factors. The second chapter deals with the origin and development of global risk assessment policies on pesticides. It focuses in particular on European policies, from the original Directive 91/414 to the current Regulation 1107/2009 and the application of the precautionary principle. A brief comparison with US approaches for risk assessment is also presented. The third chapter gives an overview on the risk assessment procedures that nowadays provide the highest achievable protection for the environment, starting with the definition of clear and specific protection goals. The fourth chapter addresses the issue of combined risk assessment of pesticides: current approaches for the evaluation of effects on non-target organisms are analysed. The last chapter is dedicated to the estimation of the environmental contamination following the application of copper –based fungicides sprayed on orchards by using MERLIN - Expo, which is a multimedia model developed in the frame of the FP7 EU project 4FUN. The performance of the MERLIN- Expo software in estimating the contamination of the metal is also analysed through a comparison with the currently used FOCUS standard models for the calculation of pesticides concentrations in surface water and sediment. Both deterministic and probabilistic simulations have been run; the latter has allowed to perform uncertainty and sensitivity assessment.

La chair de poisson et de mammifères marins constitue une source importante de protéines et de bons nutriments, tels que le sélénium (Se), la vitamine E et les acides gras polyinsaturés à longues chaînes. Cependant, la chair de ces animaux peut aussi bioaccumuler la forme organique de mercure (Hg), le méthylmercure (MeHg). Ce contaminant a fait l’objet de plusieurs études épidémiologiques, notamment en raison de sa neurotoxicité résultant d’une exposition in utero, étroitement reliée à l’ingestion de poissons fortement contaminés en MeHg. En réponse à ce risque toxicologique, les autorités sanitaires ont émis des lignes directrices quant à la consommation de poissons dans le but de protéger la population. Cependant, ces recommandations présentent certaines limites qui sont liées aux prémisses et aux omissions de l’équation déterministe utilisée pour évaluer l’exposition au MeHg par Santé Canada: (1) elles considèrent que 100% du Hg présent dans la chair de poisson est sous forme de MeHg, (2) elles supposent que le MeHg est distribué de façon homogène à l’intérieur de la chair de poisson, (3) elles prennent pour acquis que 100% du MeHg sera absorbé par le consommateur et (4) par l’utilisation d’une approche déterministe, elles omettent la potentielle incertitude et variabilité intra-populationnelle au niveau des données. L’objectif de cette thèse visait à explorer ces limites, afin de mieux comprendre l’exposition du consommateur au MeHg. Nous avons tout d’abord évalué la distribution du MeHg, du Se (antagoniste du MeHg) et de l’arsenic (As : antagoniste du Se) à l’intérieur de l’appareil musculaire d’un même poisson, en fonction de sa composition en biomolécules (protéines et lipides). Nos résultats démontrent que la présence concomitante de muscles rouges et blancs induit un gradient important de biomolécules à l’intérieur de l’appareil musculaire d’un même individu, provoquant par le fait même une variation moyenne de 2.2 fois quant à la distribution des métal(loide)s, qui se distribuent en fonction de leurs affinités biochimiques. Ces résultats confirment que le MeHg peut se distribuer de façon hétérogène à l’intérieur du muscle de poisson, ce qui pourrait mener à une sous- ou surestimation de l’exposition au MeHg pour le consommateur, en fonction de la partie du poisson qui est consommée. Par la suite, nous nous sommes attardés à l’hypothèse stipulant que 100% du MeHg est absorbé par le consommateur. Une des méthodes utilisées pour estimer la fraction de MeHg qui serait disponible à être absorbée par la paroi intestinale consiste à mesurer la bioaccessibilité, c’est-à-dire la fraction soluble de MeHg, à l’aide d’un modèle de digestion in vitro. Plusieurs études ayant utilisé cette approche observent que la cuisson de la chair de poisson diminue significativement la bioaccessibilité du MeHg, ce qui diminuerait sa potentielle absorption intestinale. Nous avons donc conduit une expérience in vivo en utilisant un modèle porcin et en parallèle, nous avons utilisé un modèle de digestion in vitro. Selon les profils sanguins porcins, la biodisponibilité orale du MeHg provenant de la chair de thon cuite n’est pas moins élevée que celle mesurée avec la chair de thon crue. En contraste, nous avons obtenu une bioaccessibilité de MeHg moins élevée avec la chair de thon cuite. Nos résultats démontrent que les modèles de digestion in vitro actuels ne sont pas suffisamment optimisés pour être utilisés directement dans les calculs d’exposition au MeHg, tels que proposés récemment dans la littérature. Finalement, nous avons testé l’impact d’ajout de variables supplémentaires dans l’équation déterministe actuellement utilisée par Santé Canada pour évaluer l’exposition du consommateur au MeHg, en conduisant une évaluation probabiliste du risque. Notamment, nous avons considéré (1) la proportion de Hg méthylée par rapport à la quantité de Hg, (2) la bioaccessibilité et (3) l’augmentation de la concentration du MeHg suite à la cuisson de la chair de poisson, créée par la perte d’humidité. Nos résultats sont clairs : chaque ajout de variable indépendante augmente ou diminue significativement l’exposition calculée, soulignant la sensibilité de l’équation utilisée pour évaluer l’exposition au MeHg. Ceci suggère que de plus amples recherches devront être conduites avant d’effectuer une quelconque modification dans l’équation de l’exposition au MeHg, par souci de ne pas sous-estimer celle-ci. Cette thèse illustre que les recommandations sont difficilement généralisables puisque la chair de poisson et de mammifères présente des propriétés différentes, en fonction de l’espèce animale considérée. Cette thèse démontre que l’équation déterministe utilisée par Santé Canada dans l’évaluation de l’exposition au MeHg devrait être mieux approfondie par la sphère scientifique, particulièrement dans le cas des mammifères marins. / Fish flesh and marine mammals is an important source of proteins and nutrients, such as selenium (Se), vitamin E and long chain polyunsaturated fatty acids. However, flesh of those animals may bioaccumulate the organic form of mercury (Hg), methylmercury (MeHg). This contaminant has been the subject of various epidemiological studies, namely because of its neurotoxicity through in utero exposure, closely related to highly MeHg contaminated fish consumption. In response to this toxicological risk, health authorities have set fish consumption guidelines in order to protect the population. Still, those guidelines present limits that are related to premises and omissions of the determinist equation used by Health Canada in order to assess the exposure to MeHg: (1) it considers that 100% of Hg in fish flesh is MeHg, (2) it supposes that MeHg is homogeneously distributed within fish flesh, (3) it takes for granted that 100% of MeHg will be absorbed by the consumer and (4) by using a determinist approach, they omit the potential uncertainty and intra-population variability in the data. The aim of this thesis was to address these limits, in order to better understand the exposure of MeHg for consumers. We first assessed the distribution of MeHg, Se (MeHg antagonist) and arsenic (As, Se antagonist) within fish musculature, as a function of its biomolecule composition (proteins and lipids). Our results demonstrated that the concomitant presence of white and red muscle induces a large gradient of protein and lipid within the muscular apparatus of the same individual. This in turn causes on average a variation by 2.2-fold regarding MeHg, Se and As bioaccumulation, which are distributed according to their biochemical affinity. Those results confirmed that MeHg can distribute heterogeneously within fish muscle, which could lead to an under- or overestimation of MeHg exposure for consumers, as function of the part of the fish consumed. Subsequently, we focused on the hypothesis stipulating that 100% of MeHg is absorbed by the consumer. A method used to assess the fraction of MeHg that would be available to be further absorbed by the gut wall consists of measuring the bioaccessibility, i.e. the soluble fraction of MeHg, using an in vitro digestion model. Several studies that assessed the bioaccessibility of cooked fish flesh observed a decreased of MeHg solubility, that would potentially diminish its intestinal absorption. However, those results have not been yet validated in vivo. To that end, we conducted an in vivo experience using the pig model and, in parallel, we used an in vitro digestion model. According to the pig’s blood profile, the oral bioavailability of MeHg from cooked tuna flesh is not less bioavailable than the MeHg from the raw tuna. Contrasting results have been found with the in vitro model, with a decrease of MeHg bioaccessibility observed when fish flesh is cooked. Our results demonstrated that in vitro digestion models are not optimized to be directly used in MeHg exposure calculus as recently proposed in the literature. Finally, we tested the impact of adding variables to the deterministic equation currently used by Health Canada to assess consumer exposure to MeHg, by conducting a probabilistic risk assessment. We considered (1) the proportion of Hg that is MeHg, (2) the MeHg bioaccessibility and (3) the increased of MeHg level after the cooking of fish flesh due to moisture loss. Our results showed that each individual variable significantly increases or decreases the calculated exposure. Thereby, it highlights the sensitivity of the equation used to assess the exposure of MeHg. It strongly suggests that more research is needed to improve Hg exposure calculation to avoid underestimating the potential health risks of MeHg exposure. This thesis presents important results regarding the exposure of MeHg through fish and marine mammals’ consumption. This thesis shows that the recommendations are difficult to generalize since the flesh of fish and mammals has different properties, depending on the animal species considered. The conclusions of this thesis demonstrate that the premises and omissions of the deterministic equation used by Health Canada in the assessment of exposure to Hg should be better investigated by the scientific sphere, especially in the case of marine mammals.

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Svenska kraftnät (Swedish National Grid) is the transmission system operator in Sweden and is responsible for maintaining and developing the Swedish transmission grid. One of the tasks included in this responsibility is transmission expansion planning, which means analyzing and planning the capacity in the future transmission grid for the requested load and generation. Historically, the N-1-criterion has been used to evaluate the reliability in transmission grid expansion planning. This criterion is deterministic, which means that all failures in the grid are considered equally, regardless of the differences in probability. In a system with an increased share of intermittent energy sources and load, it is increasingly demanding to plan and build a system that is N-1-secure in all situations. Probabilistic Risk Assessment (PRA) is a complementing method that takes the probability and consequence of different faults into consideration. The possible benefits of using PRA are higher utilization of the power grid, greater system operating flexibility, better support for system planning, and an overall optimization of socio-economic benefits. In this master thesis project, a method for PRA in transmission expansion planning at Svenska kraftnät is proposed. The method consists of three steps: generation of operating states, contingency analysis, and reliability assessment. Historical frequency and duration of faults in the transmission grid are used to estimate the probability of different contingencies. The method results in three reliability measures for the system: expected energy not supplied (MWh/year), expected duration of outages (h/year), and expected duration of overloads (h/year). The three reliability measures are combined into a composite comparison index, which can be used to compare different alternatives in transmission expansion planning. The proposed method is tested on a PSS/E model of the Swedish transmission grid and 14 different operating states. Four different investment alternatives are analyzed, including changes in load and generation, and grid reinforcements. The conclusion is that the proposed method is a useful tool for power system analysis at Svenska kraftnät and that the process for generating the operating states must be further developed. / Historiskt har det deterministiska N-1-kriteriet använts för att bedöma transmissionsnätets tillförlitlighet vid långsiktig nätplanering. Detta innebär att systemet ska dimensioneras för att klara ett bortfall av någon systemkomponent under värsta tänkbara driftfall, exempelvis topplasttimmen. I ett elsystem med alltmer intermittent förbrukning och produktion kan det dels vara svårt att veta vad som är det värsta tänkbara fallet, och dels kan det bli mycket kostsamt att dimensionera ett system som är N-1-säkert i alla lägen. Därför är det intressant att införa kompletterande probabilistiska verktyg. I detta examensjobb föreslås en metod för att beräkna och använda probabilistiska mått för att bedöma transmissionsnätets tillförlitlighet. Metoden använder flera tänkbara driftfall med varierande sannolikhet och värden på hur sannolika olika typer av fel i systemet är. Tänkbara fel analyseras och resulterar i mått på systemets förväntade överlaster och avbrott, uttryckt i timmar per år och energi per år. Dessa nyckeltal kombineras till ett sammanvägt mått, som kan användas för att jämföra olika nätanslutningar och investeringsalternativ.