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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
231

Sustainable Innovation in Forklift Design : Exploring the Mechanical Properties and Design Implications of Recycled Plastic

Wallén Hansen, Maja, Jonsson, Albert January 2024 (has links)
This master’s thesis was conducted at Linköping University in collaboration with ToyotaMaterial Handling in Mjölby to explore potential applications of recycled plastic in forklifttrucks. The primary objective was to identify the most suitable recycled plastic to be usedon the top cover of the BT Levio LWI160, which served as the focal point of this project.This was done in order to address the research questions: "What types of mechanical- andindustrial design requirements are affected when using recycled plastic (of various composi-tions), and to which new requirements and changes will result from this?" and "What are themajor mechanical- and industrial design challenges, advantages & disadvantages of switchingto recycled plastic material, considering economic and sustainability factors." The study concludes that the requirements of the top cover will largely remain unchanged.The use of PP 20GF necessitates further testing for structural integrity and quality con-sistency in recycled material. This material’s harder, less ductile nature may require newimpact testing and recycling processes. Industrial design benefits include simplified colourchoices due to the material’s transparent base hue, although the dark brown colour of re-cycled plastics limits options. Ensuring consistency across batches, minimising costs, andaddressing surface defects and purity issues are critical challenges. Despite uncertainties,switching to recycled plastic can reduce CO2 emissions by up to 24% and attract environ-mentally conscious customers
232

Investigating Rainwater Harvesting as a Stormwater Best Management Practice and as a Function of Irrigation Water Use

Shannak, Sa'D Abdel-Halim 2010 December 1900 (has links)
Stormwater runoff has negative impacts on water resources, human health and environment. In this research the effectiveness of Rain Water Harvesting (RWH) systems is examined as a stormwater Best Management Practice (BMP). Time-based, evapotranspiration-based, and soil moisture-based irrigation scheduling methods in conjunction with RWH and a control site without RWH were simulated to determine the effect of RWH as a BMP on a single-family residence scale. The effects of each irrigation scheduling method on minimizing water runoff leaving the plots and potable water input for irrigation were compared. The scenario that reflects urban development was simulated and compared to other RWH-irrigation scheduling systems by a control treatment without a RWH component. Four soil types (sand, sandy loam, loamy sand, silty clay) and four cistern sizes (208L, 416L, 624L, 833L) were evaluated in the urban development scenario. To achieve the purpose of this study; a model was developed to simulate daily water balance for the three treatments. Irrigation volumes and water runoff were compared for four soil types and four cistern sizes. Comparisons between total volumes of water runoff were estimated by utilizing different soil types, while comparisons between total potable water used for irrigation were estimated by utilizing different irrigation scheduling methods. This research showed that both Curve Number method and Mass-Balance method resulted in the greatest volumes of water runoff predicted for Silty Clay soil and the least volumes of water runoff predicted for Sand soil. Moreover, increasing cistern sizes resulted in reducing total water runoff and potable water used for irrigation, although not at a statistically significant level. Control treatment that does not utilize a cistern had the greatest volumes of predicted supplemental water among all soil types utilized, while Soil Moisture-based treatment on average had the least volume of predicted supplemental water.
233

Well testing in gas hydrate reservoirs

Kome, Melvin Njumbe 13 March 2015 (has links) (PDF)
Reservoir testing and analysis are fundamental tools in understanding reservoir hydraulics and hence forecasting reservoir responses. The quality of the analysis is very dependent on the conceptual model used in investigating the responses under different flowing conditions. The use of reservoir testing in the characterization and derivation of reservoir parameters is widely established, especially in conventional oil and gas reservoirs. However, with depleting conventional reserves, the quest for unconventional reservoirs to secure the increasing demand for energy is increasing; which has triggered intensive research in the fields of reservoir characterization. Gas hydrate reservoirs, being one of the unconventional gas reservoirs with huge energy potential, is still in the juvenile stage with reservoir testing as compared to the other unconventional reservoirs. The endothermic dissociation hydrates to gas and water requires addressing multiphase flow and heat energy balance, which has made efforts to develop reservoir testing models in this field difficult. As of now, analytically quantifying the effect on hydrate dissociation on rate and pressure transient responses are till date a huge challenge. During depressurization, the heat energy stored in the reservoir is used up and due to the endothermic nature of the dissociation; heat flux begins from the confining layers. For Class 3 gas hydrates, just heat conduction would be responsible for the heat influx and further hydrate dissociation; however, the moving boundary problem could also be an issue to address in this reservoir, depending on the equilibrium pressure. To address heat flux problem, a proper definition of the inner boundary condition for temperature propagation using a Clausius-Clapeyron type hydrate equilibrium model is required. In Class 1 and 2, crossflow problems would occur and depending on the layer of production, convective heat influx from the free fluid layer and heat conduction from the cap rock of the hydrate layer would be further issues to address. All these phenomena make the derivation of a suitable reservoir testing model very complex. However, with a strong combination of heat energy and mass balance techniques, a representative diffusivity equation can be derived. Reservoir testing models have been developed and responses investigated for different boundary conditions in normally pressured Class 3 gas hydrates, over-pressured Class 3 gas hydrates (moving boundary problem) and Class 1 and 2 gas hydrates (crossflow problem). The effects of heat flux on the reservoir responses have been addressed in detail.
234

L’altération des minéraux dans les sols forestiers du Bouclier Canadien : quels facteurs environnementaux affectent la variabilité spatiale et temporelle de la mise en solution des cations basiques?

Augustin, Fougère 07 1900 (has links)
No description available.
235

Nutrient limitation for coastal areas and estuaries in the Baltic Sea : Applying linear regression analysis and TN/TP ratio to determine the limiting nutrient / Det begränsande näringsämnet för kustområden i Östersjön : Användning av linjär regressionsanalys och TN/TP kvot för att bestämma det begränsande näringsämnet

Persson, Magnus January 2017 (has links)
The purpose of this study was to determine the limiting nutrient in a set of coastal areas and estuaries in the Baltic Sea. Although the subject as been studied for several decades, no clear consensus has been reached in the scientific community as to whether primary production is limited by phosphorus or nitrogen. A total of five coastal areas, all located on the east coast of Sweden, were assessed regarding their limiting nutrient by using three methods. The first method was applying linear regression analysis on measured TP and TN concentration together with chlorophyll-a and Secchi depth. The data was collected from sampling programs stretching back to the 1970s and 80s, studying the summer period May to September for all sites but one, were the period April to October was studied. The second method calculated the TN/TP ratio during the summer period and compared it to the Redfield ratio. Thirdly, basic mass-balance calculations were carried out, with empirical data on the external loads and calibrated with the yearly average concentration in the surface water (0–10 m). From the calculations, both the annual external and internal load of TP and TN was obtained. The different TP and TN loads were likewise tested for a correlation with the measured summer chlorophyll-a concentration and Secchi depth. The results of using linear regression analysis on measured concentrations were mostly inconclusive, as the TP and TN concentrations for all sites and most years were related to each other. Consequently both nutrients often gave equal correlation coefficients. Similarly the TP and TN loads also matched each other for most sites and years, inherently obtaining the same inconclusive, but also contradictory results, as when using the measured concentrations. The TN/TP ratio indicated, for one site that it was limited by phosphorus and another site possibly nitrogen limitation. The ratio in the other sites periodically dropped between nitrogen and phosphorus limitation over the years. Thus it was difficult to draw an overall conclusion as to what nutrient was the limiting one for all the sites. However analysing the results from the individual sites showed that three of the five sites had signs of phosphorus limitation. Two factors were deemed as being the main reasons as to why the methods did not achieve more conclusive results. The first factor was the empirical data, which varied in frequency and extent over the studied time periods and between sites, making representative concentrations difficult to calculate and evaluate. The second was the matching trends between both the concentrations and the loads of TP and TN. To achieve a better result one nutrient could be increased or decreased while one remains relatively constant. The problem with such an experiment would be controlling the inflow of nutrients from the adjacent sea. / Syftet med detta projekt var att bestämma det begränsande näringsämnet för ett antal kustområden i Östersjön. Frågan huruvida fosfor eller kväve är det begränsande näringsämnet i kustområden runt Östersjön har varit omdiskuterad under flera år och undersökts vid ett flertal tillfällen. I denna studie testades tre metoder, i fem olika kustområden, med syftet att fastställa det begränsande näringsämnet. Först användes linjär regressionsanalys med uppmätta värden på TP och TN koncentrationer tillsammans med klorofyll-a och Secchidjup. Empirisk data insamlades från övervakningsprogram där prover tagits sedan 1970- och 80-talet. Medelvärden beräknades för perioden maj till september för alla områden förutom ett, där undersöktes perioden april till oktober. Sommarmedelvärdena för TN/TP kvoten analyserades också för alla områden med avseende på Redfield kvoten. Slutligen genomfördes massbalansberäkningar med data för de externa belastningarna av TP och TN, dessa beräkningar kalibrerades sedan med uppmätta värden på koncentrationen i ytvattnet (0–10 m). Utifrån beräkningarna erhölls värden på den externa och den interna belastningen. Dessa belastningar testades med linjär regression för ett samband med de uppmätta värdena på Secchidjup och klorofyll-a. Metoden att använda linjär regressionsanalys med empiriskt uppmätta koncentrationer och djup, gav generellt ett oklart resultat. Detta var en följd av att halterna av både TP och TN i regel följdes åt, vilket fick konsekvensen att korrelationskoefficienterna för TP och TN ofta var lika stora. Samma problem uppstod för regressionsanalysen med belastningarna, då även dessa ofta följde varandra, men även motsade resultatet med koncentrationerna. Analysen av TN/TP kvoten tydde på att ett område var fosforbegränsat och ett område möjligen var kvävebegränsat. För de övriga tre områdena skiftade TN/TP kvoten under åren mellan kväve- och fosforbegränsning. De oklara resultaten gjorde det svårt att dra en övergripande slutsats. Däremot vid analysen av de enskilda områdena uppvisade tre av de fem områdena tecken på fosforbegränsning, även om detta inte kunde med säkerhet fastställas. Det var huvudsakligen två faktorer vars inverkan anses ha haft stor betydelse för det oklara resultatet. Den första faktorn var uppmätt data, vars frekvens och omfattning skiljde sig avsevärt mellan år och platser. Följaktligen försvårades beräkningarna av koncentrationerna och tillförlitligheten i hur representativa värdena var. Den andra och avgörande faktorn var de matchande trenderna hos både koncentrationerna och belastningarna. För att förbättra resultatet kan ett näringsämne ändras, medan det andra näringsämnet hålls relativt konstant. Problemet med att genomföra ett sådant experiment skulle vara att kontrollera inflödet av näringsämnen från närliggande hav.
236

PCB i Oxundasjön och Rosersbergsviken : Prediktiv modellering av återhämtningsscenarier

Hållén, Joakim January 2016 (has links)
A regional survey of environmentally harmful substances in fish in autumn 2013 revealed elevated levels of polychlorinated biphenyls (PCBs) in perch from Lake Oxundasjön, north of Upplands Väsby in Stockholm County. Follow-up studies have shown that the quantity of PCBs contained in the lake is unique of its kind in Sweden, and that the area of influence also includes downstream Rosersbergsviken, a bay of Lake Mälaren. The elevated concentrations in fish exceed today's market limits and environmental quality standards for PCBs, as of this, responsible authorities discourage from consumption of fish from Lake Oxundasjön and Rosersbergsviken. The aim has been to use statistical analyses and mass-balance modelling to study the current state of the lake system and how it may evolve in the future under different circumstances. There is a statistically significant correlation between PCB levels in sediment and perch from 21 different sites in the Stockholm-Mälaren region, including Lake Oxundasjön and Rosersbergsviken, this was demonstrated with a linear regression model. With the multivariate analysis method principal component analysis (PCA), it was illustrated how the contaminant levels in fish from Lake Oxundasjön and Rosersbergsviken differed on contaminant levels in fish from other sites. The difference mainly concerned the size and composition of PCBs. Mass-balance modelling of quantities and flows of PCBs in Lake Oxundasjön and Rosersbergsviken was made in the simulation program STELLA®. The modelling indicated that the system currently serves as a secondary distribution source of PCBs to the environment. The recovery of PCB levels is slow in the system, it will take more than 25 years for concentrations in fish to reach today’s market limits and environmental quality standards for PCBs. The model was used to evaluate three different treatment methods for Lake Oxundasjön: dredging, capping and activated carbon treatment. Simulations of these treatments led to a substantial improvement of the PCB situation in Lake Oxundasjön. Moreover, they also had a positive impact on the recovery process in the downstream Rosersbergsviken. Future climate changes, with warmer temperatures and higher run off, led to a slightly faster recovery progress of PCBs in the system.
237

Well testing in gas hydrate reservoirs

Kome, Melvin Njumbe 16 January 2015 (has links)
Reservoir testing and analysis are fundamental tools in understanding reservoir hydraulics and hence forecasting reservoir responses. The quality of the analysis is very dependent on the conceptual model used in investigating the responses under different flowing conditions. The use of reservoir testing in the characterization and derivation of reservoir parameters is widely established, especially in conventional oil and gas reservoirs. However, with depleting conventional reserves, the quest for unconventional reservoirs to secure the increasing demand for energy is increasing; which has triggered intensive research in the fields of reservoir characterization. Gas hydrate reservoirs, being one of the unconventional gas reservoirs with huge energy potential, is still in the juvenile stage with reservoir testing as compared to the other unconventional reservoirs. The endothermic dissociation hydrates to gas and water requires addressing multiphase flow and heat energy balance, which has made efforts to develop reservoir testing models in this field difficult. As of now, analytically quantifying the effect on hydrate dissociation on rate and pressure transient responses are till date a huge challenge. During depressurization, the heat energy stored in the reservoir is used up and due to the endothermic nature of the dissociation; heat flux begins from the confining layers. For Class 3 gas hydrates, just heat conduction would be responsible for the heat influx and further hydrate dissociation; however, the moving boundary problem could also be an issue to address in this reservoir, depending on the equilibrium pressure. To address heat flux problem, a proper definition of the inner boundary condition for temperature propagation using a Clausius-Clapeyron type hydrate equilibrium model is required. In Class 1 and 2, crossflow problems would occur and depending on the layer of production, convective heat influx from the free fluid layer and heat conduction from the cap rock of the hydrate layer would be further issues to address. All these phenomena make the derivation of a suitable reservoir testing model very complex. However, with a strong combination of heat energy and mass balance techniques, a representative diffusivity equation can be derived. Reservoir testing models have been developed and responses investigated for different boundary conditions in normally pressured Class 3 gas hydrates, over-pressured Class 3 gas hydrates (moving boundary problem) and Class 1 and 2 gas hydrates (crossflow problem). The effects of heat flux on the reservoir responses have been addressed in detail.
238

Optimisation des marais filtrants pour l’abattement du pesticide chlorantraniliprole du ruissellement agricole

Abas, Khalil 02 1900 (has links)
Au cours des dernières décennies, une grande variété de pesticides émergents, tels que le chlorantraniliprole (CAP), ont été introduits malgré le manque de connaissance approfondie de leur risque écotoxicologique. Les marais filtrants (TW) sont des technologies écologiques et durables qui ont montré un grand potentiel d’atténuation des polluants agricoles communs, tels que les pesticides dans le ruissellement. L’objectif de cette étude était d’optimiser l’utilisation du marais filtrant sous-surfacique à écoulement horizontal (HSSF) en déterminant: a) l'effet d’un amendement de biochar au substrat et b) la performance de trois espèces de macrophytes (Phragmites australis subsp. americanus, Scirpus cyperinus et Sporobolus michauxianus) dans l'abattement du CAP du ruissellement agricole. L'efficacité d'abattement a été calculée en utilisant la méthode du bilan de masse dans des mésocosmes HSSF matures alimentés avec un ruissellement agricole synthétique contenant du CAP pendant une période d'un mois. Les mésocosmes avec l’ajout de biochar se sont avérés très efficaces dans l’abattement du CAP (90 à 99%) et ils le sont restés tout au long de la période expérimentale. Cette efficacité est probablement due à la grande capacité d’adsorption du biochar, bien que ce mécanisme n’ait pas été directement mesuré. En revanche, l'abattement du CAP dans les mésocosmes plantés sans biochar était faible et limité et il n’y avait pas de différence entre les espèces, bien qu’elles aient eu des différences dans leur biomasse aérienne et leur taux d'évapotranspiration (ET). Cependant, les traitements plantés ont agi comme zone tampon, en atténuant la masse du CAP de l'influent et en la libérant lentement dans l'effluent. Le taux d'ET de Scirpus et Phragmites était plus élevé que celui de Sporobolus, ce qui s’est traduit par un meilleur effet tampon. Cette étude suggère que l'ajout de biochar au substrat HSSF TW est prometteur pour l'atténuation du CAP dans le ruissellement agricole, mais leur efficacité à long terme reste à être étudiée. Malgré tout, les TW devraient être utilisés comme un outil complémentaire, dans le cadre d'actions plus larges visant à réduire la pression des polluants sur les écosystèmes aquatiques. / Over the past decades, a wide variety of emergent pesticides, such as chlorantraniliprole (CAP), have been introduced despite the lack of in-depth knowledge of their ecotoxicological risk. Treatment wetlands (TWs) are environmentally friendly and sustainable technologies that have shown great potential to mitigate common agricultural pollutants, such as pesticides in runoff. The objective of this study was to optimize the use of the horizontal subsurface flow treatment wetlands (HSSF TWs) by determining a) the effect of biochar amendment to the substrate and b) the performance of three species of macrophytes (Phragmites australis subsp. americanus, Scirpus cyperinus and Sporobolus michauxianus) in CAP removal from agricultural runoff. The removal efficiency was calculated using the mass balance method in mature HSSF mesocosms fed with synthetic agricultural runoff containing CAP for a period of one month. Mesocosms with the addition of biochar were very effective in removing CAP (90-99%) and remained so throughout the experimental period. This efficiency is likely due to the high adsorption capacity of biochar, although this mechanism has not been directly measured. In contrast, CAP removal in mesocosms planted without biochar was low and limited and there was no difference between species, although there were differences in their above-ground biomass and their evapotranspiration (ET) rate. However, the planted mesocosms acted as buffer zones, reducing the CAP mass of the influent and slowly releasing it into the discharge. The ET rate of S. cyperinus and P. australis was higher than that of S. michauxianus, resulting in a better buffering effect. This study suggests that adding biochar to the HSSF TW substrate is promising for CAP attenuation in agricultural runoff, but their long-term effectiveness remains to be investigated. Nevertheless, TWs should be used as a complementary tool, as part of wider actions aimed at reducing the pressure of pollutants on aquatic ecosystems.
239

Lean production in the aggregate stone industry: The road to becoming more sustainable and productive : A case study for a Swedish construction company

Abrahamsson, Ludwig, Ramsten, Oscar January 2022 (has links)
The aggregate stone industry produces stone – a critical material for the construction industry value chain, and is, thus, a valuable resource for building materials, highlighting the society’s need for critical products. The stone is mined and refined in so-called quarries. Yet, the industry is classified as an environmentally hazardous activity as it has traditional ways of consuming fossil fuels. Given that the industry is hazardous, the aggregate stone business needs to become more sustainable.  This master's thesis was carried out at a large Swedish construction company and the aggregate stone industry. Where perceptions of challenges around sustainability, and productivity were studied, these three pillars have permeated the work. Due to the hazardous industry, there is a need to reconcile and implement related tensions concerning Lean principles and circular economy in the traditional industries as construction. Because sustainability is the praxis in today's society. Since the process changes have a significant role in Lean, which strives to create flows and minimise waste of resources through various efficiencies. In order to make the industry more sustainable, the circular economy is an approach for maintaining a favourable environment and reducing waste, as well as adopting useful mechanisms and processes as recycling and reuse. This study focuses on the economic and environmental aspects of sustainability. Based on the study results, the aggregate stone industry should adapt its organisation to work towards the Lean principles and circular economy to be more favourable in these two aspects. Data were collected through interviews with experts in the aggregate stone industry and through observations at selected facilities. Production and workflow in the industry should be prioritised to focus on developing the six themes examined across the value-chain: location, machinery, resources, communication and information, the employees and finally, the end-user. Increased awareness and knowledge in these areas and sustainability would mean better conditions for the companies to invest in financial and environmental resources to achieve a competitive advantage – a leading role in the industry. / Stenindustrin producerar sten – vilket är ett kritiskt material för byggbranschens värdekedja, och är därmed en värdefull resurs för byggmaterial som lyfter fram samhällets behov av kritiska produkter. Stenen bryts och förädlas i så kallade stenbrott. Trots allt klassas branschen som en miljöfarlig verksamhet eftersom den har traditionella sätt att konsumera fossila bränslen, vilket leder till att stenverksamheten behöver bli mer hållbar. Detta examensarbete har genomförts på ett stort svenskt byggföretag och inom stenindustrin. Där uppfattningar om utmaningar kring hållbarhet och produktivitet har studerats vilket har genomsyrat arbetet. I och med den miljöfarliga branschen finns det ett behov av att förena och implementera förändringar relaterade till teorier. Teorierna Lean och cirkulär ekonomi kan anses som ett traditionellt sätt för att motverka den miljöfarliga branschen som bygg- och anläggningsbranschen upprätthåller, då hållbarhet är en praxis i dagens samhälle. Givet de betraktade teorier, har processförändringar en betydande roll inom Lean, som strävar efter att skapa flöden och minimera slöseri med resurser genom olika effektiviseringar. För att göra branschen mer hållbar är den cirkulära ekonomin ett tillvägagångssätt för att upprätthålla en gynnsam miljö och minska avfallet, samt upprätthålla användbara mekanismer och processer som återvinning och återanvändning. Denna studie fokuserar på de ekonomiska och miljömässiga aspekterna inom hållbarhet. Baserat på studieresultaten bör stenmaterialsindustrin anpassa sin organisation för att arbeta mot Lean-principerna och den cirkulära ekonomin för att vara mer gynnsam i dessa två aspekter. Data samlades in genom intervjuer med experter inom bergtäktsindustrin och genom observationer på utvalda anläggningar. Produktion och förvaltning bör prioriteras i branschen för att fokusera på att utveckla de sex teman som granskas över hela värdekedjan: plats, maskiner, resurser, kommunikation och information, de anställda och slutligen slutanvändaren. Ökad medvetenhet och kunskap inom dessa områden och hållbarhet skulle innebära bättre förutsättningar för företagen att investera i ekonomiska och miljömässiga resurser för att uppnå en konkurrensfördel– en ledande roll inom branschen.
240

Evaluating the use of dose-response relationships based on in vitro data in establishing acceptable exposure levels in humans

Bloch, Sherri 09 1900 (has links)
Avec plus de 350 000 produits chimiques utilisés et de nouveaux arrivant sur le marché chaque année, des outils rapides et à coûts réduits sont nécessaires pour l'étude de ces produits. L’évaluation des risques pour ces produits est généralement faite à partir d’études animales, mais celles-ci présentent plusieurs limitations. Par exemple, évaluer le potentiel cancérogène d’une substance prendre jusqu'à trois ans et coûter six millions de dollars. En outre, il a été démontré que les modèles animaux n'ont qu'un faible pouvoir prédictif par rapport aux effets chez l’humain. Pour surmonter ces obstacles, on assiste actuellement à un mouvement mondial en faveur du développement et de l'acceptation de nouvelles approches méthodologiques (NAM) pour la priorisation des produits chimiques et l'évaluation des risques. Notre objectif était d’élaborer et d'évaluer une nouvelle approche d’extrapolation in vitro à in vivo (IVIVE) pour établir des niveaux d'exposition acceptables chez l'homme en combinant des des études in vitro et des outils de modélisation toxicologique. À cette fin, nous avons développé et évalué un outil informatique utilisé dans l'approche IVIVE et mené des études de cas sur deux produits chimiques pour lesquels étaient disponibles des données in vitro, des modèles d'exposition, et des études épidémiologiques associant l’exposition à des effets néfastes chez l’humain. Dans le premier article, nous avons développé et évalué un modèle de bilan de masse dynamique (IV-MBM DP v1.0) pour estimer les concentrations intracellulaires au cours d'expériences in vitro avec administration répétée, incluant une description du transport facilité. Pour évaluer la précision du modèle, nous avons paramétré et appliqué le modèle à des scénarios de dose unique et de doses répétées, et évalué les concentrations estimées aux données empiriques. En outre, nous avons simulé des scénarios de dosage répété pour des produits chimiques organiques représentant une diversité de caractéristiques physico-chimiques, et nous avons comparé leur dispersion dans le système au fil du temps. Dans l'ensemble, pour les scénarios de dosage unique et répété, la concordance entre les données simulées et expérimentales a illustré le pouvoir prédictif du modèle. i Dans les deuxième et troisième articles, nous nous sommes concentrés sur l'utilisation et l'évaluation de notre nouvelle approche IVIVE en faisant deux études de cas impliquant l'exposition placentaire et lactationnelle à des polluants organiques persistants. La première étape de notre méthodologie a été la sélection d'un point de départ à partir d'une étude in vitro utilisant des cellules humaines. Ensuite, nous avons appliqué la modélisation benchmark dose pour obtenir la concentration associée à un changement relatif de 5% de la réponse par rapport au contrôle. Nous avons ensuite appliqué la modélisation de de bilan de masse pour déterminer la concentration cellulaire pour un point de départ conduisant à un changement de réponse de 5%. Un modèle toxicocinétique pour le transfert placentaire et par l’allaitement a ensuite été utilisé pour calculer la dose équivalente administrée et la concentration plasmatique associée, et des facteurs d'incertitude (variabilité interindividuelle (10) et sous-chronique à chronique (10)) ont été appliqués pour calculer les apports quotidiens tolérables et les équivalents de biosurveillance. Les équivalents de biosurveillance ont été comparés aux concentrations dans le sang de la mère et du cordon ombilical mesurées dans les études épidémiologiques. Nos études de cas portaient sur la neurotoxicité développementale du 2,2',4,4'-tétrabromodiphényléther (BDE-47) et sur l'obésogénicité du dichlorodiphényldichloroéthylène (p,p'-DDE). Pour les deux études, les apports quotidiens tolérables calculés en tenant compte des facteurs d’incertitude étaient plus faibles que les valeurs toxicologiques de référence déterminées sur la base d’études animales. En outre, les deux études de cas ont produit des équivalents de biosurveillance se situant dans la gamme des concentrations maternelles et du cordon ombilical mesurées dans les études épidémiologiques. Dans l'ensemble, l'évaluation de notre modèle de bilan de masse, ainsi que les valeurs conservatrices générées par l'approche IVIVE dans nos études de cas, renforcent la confiance dans les NAM, ce qui est essentiel pour leur adoption future par les organismes de réglementation. / With over 350,000 chemicals in use and more entering the market every year, cost-effective and time-efficient tools are necessary for the investigation of these products. Whole animal models are traditionally used and accepted by regulatory agencies; however, animal models carry multiple limitations. Specifically, animal models may take up to three years and six million dollars to investigate the carcinogenicity of a compound. Additionally, animal models have been shown to have poor predictive power for human safety. To overcome these obstacles, a global movement toward the development and acceptance of new alternative methods (NAMs) for chemical prioritization and risk assessment is taking place. Our objective was to develop and evaluate a novel in vitro to in vivo (IVIVE) approach to establish acceptable exposure levels in humans by combining novel in vitro and biological/computational modeling technologies for chemical safety assessment. To this end, we tested and evaluated a computational tool utilized in the IVIVE approach, and conducted proof-of-concept studies on two case chemicals with publicly available in vitro data, exposure models, and epidemiological studies demonstrating adverse health effects. In the first paper, we aimed to develop and evaluate a dynamic partitioning mass-balance model (IV-MBM DP v1.0) to estimate intracellular concentrations during in vitro experiments of repeat dosing, and incorporate facilitated transport into the model. To evaluate the model accuracy, we parametrized and applied the model to single dose and repeat dosing scenarios and assessed the output against empirical data. In addition, we simulated repeat dosing scenarios for organic chemicals with different properties and compared their dispersion within the system over time. Overall, for single and repeat dosing scenarios, concordance between simulated and experimental data illustrated the predictive power of the model. In the second and third papers, we focused on the use and evaluation of our novel IVIVE approach through case studies involving placental and lactational exposure to persistent organic pollutants. The first step of our methodology was the selection of a point of departure from an in vitro study utilizing human cells. Next, we applied benchmark dose modeling to obtain the nominal iv concentration at a 5% relative change in response from control. We subsequently applied mass- balance modeling to determine the cellular concentration for the POD leading to a 5% change in response. A toxicokinetic model for placental transfer and lactation was then used to calculate the administered equivalent dose and associated maternal and cord plasma concentration, and uncertainty factors (interindividual variability (10) and subchronic to chronic (10)) were applied to calculate tolerable daily intakes and biomonitoring equivalents. Biomonitoring equivalents were compared to concentrations in maternal and cord blood measured in epidemiological studies. Our case studies were on 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) developmental neurotoxicity and dichlorodiphenyldichloroethylene (p,p’-DDE) obesogenicity. For both studies, calculated tolerable daily intakes accounting for uncertainty factors were more conservative than the reference doses determined through the use of whole animal models. Moreover, both case studies produced biomonitoring equivalents within the range of maternal and cord levels measured in epidemiological studies. Overall, assessment of our IV-MBM DP v1.0 mass-balance model, as well as the demonstrated protective quality of the IVIVE approach in our case studies, enhances confidence in NAMs, which is essential for their future adoption by regulatory agencies.

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