Thèses sur le sujet « Toxicodynamie »
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Mit, Corentin. « Modélisation mécaniste de la dynamique de biomarqueurs chez les poissons téléostéens : lien entre exposition et effetsprécoces ». Electronic Thesis or Diss., Paris, AgroParisTech, 2023. http://www.theses.fr/2023AGPT0001.
Texte intégralBiomarkers are useful tools for the diagnosis of environmental risk in aquatic ecosystems. Nevertheless, the measurement of these sub-individual markers still presents some limitations for the assessment of ecosystem health, including the characterisation of the complex dynamics of responses of these non-lethal effects as a function of time or dose, or the extrapolation of responses from one scale of biological organisation to another. One of the solutions that seems promising for characterising the dynamics of these responses from a change of scale perspective would be to integrate the biomarkers into mechanistic models that make it possible to predict these dynamics and explain the mechanisms underlying the effects. This thesis proposes to build mechanistic models of physiologically based toxicokinetics and toxicodynamics (PBTK-TD) to better characterise and understand the response dynamics of biomarkers. In this context, the problem of biomarker dynamics was divided in two. First, the "toxico-kinetic" or TK makes it possible to link the external dose, present in the environment, to the internal dose, present in the organism. Second, the "toxico-dynamic" or TD, makes the link between the internal dose and the effect. Accordingly, the first step in this thesis was to collect a set of TK and TD data in our model species, the three-spined stickleback, on a family of compounds, the bisphenols, and more specifically, BPA, BPS and BPF. These data, collected from short-term exposures (seven days of contamination and seven days of depuration) and long-term exposure (21 days), were used to compare the modulating effects of bisphenols on biomarkers. In particular, markers of innate immunity were strongly impacted by these substances. Differences in kinetics between BPA and BPS were also highlighted. Subsequently, the data collected during the exposures were used to build a physiologically based TK model (PBTK) for BPA, then a PBTK model coupled with TD sub-models (PBTK-TD) describing the dynamics of certain immunomarkers in the stickleback. Finally, a last PBTK-TD model was built to demonstrate the feasibility of this modelling approach for integrating exposure conditions more representative of those in the natural environment, i.e. for a mixture of substances. Taken as a whole, this thesis demonstrates the attractiveness of coupling the experimental approach consisting in measuring biomarkers and modelling
Chaumet, Betty. « Transfert et distribution des pesticides dans les biofilms en lien avec les effets toxiques associés ». Thesis, Bordeaux, 2018. http://www.theses.fr/2018BORD0223/document.
Texte intégralIn 2000, the Water Framework Directive required the return of rivers to good chemical and ecological status. In particular, it has classified 45 substances as priority for this assessment (Directive 2013/39/EU), including a large proportion of pesticides. Indeed, due to their massive use, these contaminants are now found in all compartments of the environment. In addition, given its ability to integrate contamination, biofilm is considered an excellent bioindicator for water quality assessment. It is at the base of the trophic chain in aquatic environments and is composed of microorganisms (microalgae, bacteria, fungi, etc...) embedded in a matrix of extracellular polymeric substances (EPS).This thesis focused on the analysis of mechanisms of pesticide transfer and distribution in biofilms related to toxic impacts. This work was carried out using a toxicokinetic approach whereby the bioaccumulation of diuron (a photosynthesis inhibitor herbicide) was monitored in the different compartments of the biofilm. This assessment was carried out under several abiotic conditions (flow velocity, temperatures and photoperiods) under varying exposure durations. In parallel, functional and structural descriptors were measured as photosynthetic (for autotrophic communities) and enzymatic (for heterotrophic communities) activities, as well as biofilm biomass and protein and polysaccharide production.All the experiments performed during this thesis made it possible to highlight the sorption mechanisms of diuron in biofilm, i.e. absorption processes by cells and adsorption phenomenon within the EPS matrix. Then the influence of the different environmental parameters studied was emphasized. This work demonstrates the relevance of the toxicokinetic-toxicodynamic approach to the study of the impact of pesticides on fluvial biofilms
Lewandowski, Thomas A. « Toxicokinetic and toxicodynamic modeling of the effects of methyl mercury on development of the embryonic rat midbrain / ». Thesis, Connect to this title online ; UW restricted, 2000. http://hdl.handle.net/1773/8450.
Texte intégralEverett, Scott D. « The Pharmacodynamics and Toxicodynamics of Inotropic Drugs in Calves With Natural and Artificial Hearts ». DigitalCommons@USU, 1994. https://digitalcommons.usu.edu/etd/4103.
Texte intégralBerggren, Kristina. « Toxicity of chlorantraniliprole to the Collembola Folsomia candida : toxicodynamics and effects of organic matter content ». Thesis, Mittuniversitetet, Avdelningen för naturvetenskap, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:miun:diva-24243.
Texte intégralHeine, Simon [Verfasser]. « Development and specification of a toxicokinetic and toxicodynamic growth model of Myriophyllum spicatum for use in risk assessment / Simon Heine ». Aachen : Hochschulbibliothek der Rheinisch-Westfälischen Technischen Hochschule Aachen, 2014. http://d-nb.info/1065353502/34.
Texte intégralDogruer, Gulsah. « Assessing the impact of chemical exposure on the health of endangered sea turtles through toxicokinetics and toxicodynamics ». Thesis, Griffith University, 2022. http://hdl.handle.net/10072/420901.
Texte intégralThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Environment and Sc
Science, Environment, Engineering and Technology
Full Text
Collet, Séverine. « Développement d’une approche toxicocinétique/toxicodynamique basée sur des mécanismes physiologiques pour évaluer les effets oestrogéniques du Bisphénol A ». Thesis, Toulouse, INPT, 2012. http://www.theses.fr/2012INPT0001/document.
Texte intégralThe goal of this thesis was to analyse through toxicokinetic (TK) and mechanistic approaches the estrogeno-mimetic effects of bisphenol A (BPA) on a precocious and sensitive biomarker: LH secretion in ovariectomized female lambs. The lowest plasma BPA concentrations associated to an inhibition of LH secretion appeared to be close to the highest one reported in human. LH suppression could be mediated by an inhibition of hypothalamic kisspeptin systems. The multispecies TK approach showed that BPA clearance is always high and equivalent to the liver blood flow. For an exposure scheme corresponding to the tolerable daily intake, this approach allows to predict human BPA concentration much lower than the one associated to LH inhibition in our highly sensitive lamb model
Black, Paleah. « Interactions of Dietary Antioxidants and Methylmercury on Health Outcomes and Toxicodynamics : Evidence from Developmental Rat Model Studies and Human Epidemiology ». Thèse, Université d'Ottawa / University of Ottawa, 2011. http://hdl.handle.net/10393/19874.
Texte intégralGajewska, Monika Anna [Verfasser], Karl-Werner [Akademischer Betreuer] [Gutachter] Schramm et Heiko [Gutachter] Briesen. « Physiologically-based toxicokinetic and toxicodynamic modelling of single and repeated dose toxicity / Monika Anna Gajewska. Betreuer : Karl-Werner Schramm. Gutachter : Karl-Werner Schramm ; Heiko Briesen ». München : Universitätsbibliothek der TU München, 2015. http://d-nb.info/1101695188/34.
Texte intégralUrtizberea, Michel. « Intoxication aigûe par les hétérosides cardiotoniques : contribution à son traitement par le développement d'un fragment monoclonal anti-digitoxine et modélisation toxicocinétique-toxicodynamique ». Paris 5, 1990. http://www.theses.fr/1990PA05P621.
Texte intégralSchmidt, Jens. « Wirkung von Umweltchemikalien auf Gammarus fossarum - Populationsexperimente und individuenbasiertes Reproduktionsmodell ». Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2004. http://nbn-resolving.de/urn:nbn:de:swb:14-1090321181000-52636.
Texte intégralSchmidt, Jens. « Wirkung von Umweltchemikalien auf Gammarus fossarum - Populationsexperimente und individuenbasiertes Reproduktionsmodell ». Doctoral thesis, Technische Universität Dresden, 2003. https://tud.qucosa.de/id/qucosa%3A24352.
Texte intégralSilva, Bárbara Sofia Poléri da. « Enantioselectivity of pentedrone and methylone : enantioresolution by liquid chromatography and in vitro toxicokinetic/toxicodynamic studies ». Tese, 2021. https://hdl.handle.net/10216/136398.
Texte intégralSilva, Bárbara Sofia Poléri da. « Enantioselectivity of pentedrone and methylone : enantioresolution by liquid chromatography and in vitro toxicokinetic/toxicodynamic studies ». Doctoral thesis, 2021. https://hdl.handle.net/10216/136398.
Texte intégralChen, Chi-Yun, et 陳季芸. « Toxicokinetic/toxicodynamic modeling and exposure risk assessment for aquatic organisms and mice posed by polystyrene microplastics ». Thesis, 2019. http://ndltd.ncl.edu.tw/handle/c3g4ws.
Texte intégral國立臺灣大學
生物環境系統工程學研究所
107
Microplastics (MPs), are defined as tiny plastics with particle size less than 5 mm. Ecological concerns and health risks of MPs contamination have been attracting a worldwide attention within a decade. While a large body of literature has shown that MPs are highly likely to be accumulated in aquatic and terrestrial biota, information about the toxic interactions of MPs on organisms from a mechanistic point of view is more limited. This thesis filled this knowledge gap by assessing polystyrene (PS)-MPs in zebrafish, red tilapia, and mice systems based on a toxicokinetic/toxicodynamic (TK/TD) modeling to quantify organ-bioaccumulation and biomarker responses appraised with published datasets. Exposure risks for aquatic model organisms including bivalves were also presented by utilizing the published environmentally relevant concentration data of PS-MPs in marine and freshwater ecosystems. The organ-specific TK-parameters and mean residence times for zebrafish, red tilapia, and mice posed by size-specific PS-MPs could be obtained. The highest uptake rates were in the liver of zebrafish, in the gut of red tilapia and mice, respectively. Results showed that steady-state bioconcentration factors (BCFsss) of PS-MPs among all organs were much greater than 1, indicating the bioaccumulating potential of PS-MPs in animals. In comparison to mice, zebrafish have commonly much greater BCFsss in organs. The sensitivities of biomarkers regarding immunological response, oxidative stress, detoxification, and energy and lipid metabolisms to PS-MPs in liver of organisms were determined by the TD assessment. These concentration-effect relationships based on the Hill model varied with species used, exposure time, and particle size of PS-MPs in each system. As the result, toxicity thresholds of PS-MPs were in a large variability. Results demonstrated that the most sensitive biomarkers in bivalves, zebrafish, red tilapia, and mice systems, based on strict threshold concentrations, were phagocytic cells, superoxide dismutase (SOD), 7-ethoxyresorufin O-deethylase, and SOD, respectively. A risk-based probabilistic model was further used to characterize the potential hazards of marine bivalves and freshwater fish in response to predicted environmental concentrations of PS-MPs quantified by exceedance risks and risk quotients. Among five global plastic-filled gyres, the highest and lowest risks were occurred in the North Pacific and South Pacific Oceans for bivalves, respectively. For freshwater fish, the Winyah Bay in USA appeared to be the greatest risks among the selected local areas. The present results warranted further attention on worldwide MPs pollution posing hazards to aquatic organisms, particularly sensitive species like zebrafish taking the brunt of the long-term toxicity risk. Moreover, the mice-based TK parameters and threshold criteria greatly assist in designing robust researches to evaluate MPs consumption by humans. An extrapolation framework was proposed for mechanistically estimating toxicity thresholds of MPs from mice to humans in a health risk assessment perspective. Overall, results derived from the TK/TD assessment, the Weibull threshold model, and the ecotoxicological risk assessment could be adopted to rapidly evaluate MPs-induced toxicities at various concentrations. The strict thresholds could be recommended as criteria for environmental management of MPs and offer a tool-kit in establishing the scheme for risk assessment of human consumption.
Ju, Yun-Ru, et 朱韻如. « Subcellular Partitioning Links Toxicokinetic/toxicodynamic Models to Assess the Susceptibility Risk in Farmed Fish Exposed to Metal Stressors ». Thesis, 2012. http://ndltd.ncl.edu.tw/handle/38765924750544317348.
Texte intégral國立臺灣大學
生物環境系統工程學研究所
100
Recently, subcellular metal partitioning has been used for assessing metal toxicity in aquatic organisms. In reality, the environmental metal concentration is tended to be fluctuation and pulse as a result of the site-specific water chemistry conditions. But little researches have been studied by using the subcellular partitioning for aquatic organisms exposed to pulsed metals in the field of ecotoxicology. Hence, the purposes of this dissertation were: (i) to develop an integrated toxicological model by linking subcellular partitioning and toxicokinetic/toxicodynamic (TK/TD) models with the experimental data of pulsed copper (Cu)-tilapia (Oreochromis mossambicus) system and published data of cadmium (Cd)-rainbow trout (Oncorhynchus mykiss) system, (ii) to investigate the trade-offs among ecophysiological parameters related to metals bioaccumulation, subcellular partitioning, and susceptibility in farmed fish of tilapia and rainbow trout, and (iii) to provide a probabilistic risk approach to assess susceptibility risks for farmed fish exposed to metals stressors. A 28-day pulsed Cu exposure experiment was conducted to provide the information on the subcellular partitioning of Cu in tilapia. The Cu bioaccumulation and the distributions of Cu in metabolically active (MAP) and detoxified pools (MDP) can be obtained from the pulsed Cu exposure experiment. The published data of rainbow trout exposed to waterborne and dietborne Cd were adopted to reanalyze and estimate susceptibility and detoxified capacity. This study estimated bioavailability, bioaccumulation, and internal damage of tilapia and rainbow trout in response to pulsed Cu and Cd, respectively. Toxicokinetic parameters of uptake rate (k1), elimination rate (k2), and detoxification rate constants (kd) were derived for tissues in tilapia (gill and muscle) and rainbow trout (gill, liver, and gut). The damage assessment model (DAM) was used to fit to data of time-varying percentage of metal in MAP to estimate killing rate constant (kk), recovery rate constant (kr), and susceptibility. A physiological-based TK model was used to predict tissue burdens for rainbow trout exposed to environmentally relevant Cd concentrations and tissue-specific susceptibility risks can be estimated. A probabilistic risk assessment model was presented to assess the metal exposure risks for tilapia and rainbow trout. The experimental results indicated that the percentage of Cu in MAP increased with time from 23% to 57% for gill, whereas for muscle, the percentage of Cu in MAP slightly decreased with time from 35% to 28% for tilapia in response to pulsed Cu exposure. Results showed that toxicokinetic parameters of k1s, k2s, and kds were 8.38 and 0.408 mL g-1 d-1, 0.244 and 0.031 d-1, and 0.178 and 0.033 d-1, respectively, for gill and muscle of tilapia exposed to pulsed waterborne Cu. Results showed that k2, kd, and kr ranged from 0.32 – 0.46 d-1, 0.45 – 1.72 d-1, and 1.08 – 1.45 d-1, respectively, for gill of rainbow trout exposed to waterborne Cd (5 – 50 ug L-1), whereas 0.07 – 0.19 d-1, 2.24 – 87.75 d-1, and 1.02×10-6 – 1.37×10-2 d-1, respectively, for gut exposed to dietborne Cd (0.6 – 30.3 ug g-1). This study implicated no significant susceptibility risk for tilapia exposed to waterborne Cu concentrations. The probability that 50% or more of the susceptibility risk in response to Cu exposure for tilapia was only 33.2% Cu in MAP. For rainbow trout exposed to Cd, a most likely probability of % Cd in MAP of gill and liver exceeding 47 – 49%. In contrast with gill and liver, gut had a relative lower Cd susceptibility risk (15 – 17% Cd in MAP). The trade-offs between elimination and detoxification in rainbow trout exposed to Cd, Cu, and zinc (Zn) based on recently published data were also examined. Results indicated that the relationships between k2 and kd were negative for rainbow trout. However, the relationships between kd and % metal in MDP were found to be positive. Results also indicated that rainbow trout had the higher accumulation (~ 60 – 90 %) in MAP when exposed to essential metals of Cu and Zn and had only 10 – 50 % accumulation in response to non-essential metal of Cd. This study found that metal accumulations of tissues varied with the patterns of exposure metal concentration in farmed fish. An integrated model to assess the susceptibility for farmed fish exposed to metal stressors was provided in this study. The trade-offs between elimination and detoxification were also quantified for providing the valuable insights into the ecotoxicology of farmed species. In conclusion, this study used exposed laboratory data of Cu and Cd to investigate the bioaccumulation, bioavailability, and metal distribution of subcellular partitioning for understanding of the susceptibility risks in framed fish of tilapia and rainbow trout. Hence, the probabilistic risk assessment framework linking with the proposed integrated ecotoxicological model can provide an advice for helping government based bioassessment and biomonitoring programs to protect the farmed fish from metal exposures.
Jeng-Wei, Tsai. « Bioenergetics- and Physiologically-Based Toxicokinetics/Toxicodynamics and Mode of Action of Arsenic Toxicity to Tilapia Oreochromis mossambicus ». 2005. http://www.cetd.com.tw/ec/thesisdetail.aspx?etdun=U0001-0507200510031600.
Texte intégralTsai, Jeng-Wei, et 蔡正偉. « Bioenergetics- and Physiologically-Based Toxicokinetics/Toxicodynamics and Mode of Action of Arsenic Toxicity to Tilapia Oreochromis mossambicus ». Thesis, 2005. http://ndltd.ncl.edu.tw/handle/97704139521026828513.
Texte intégral國立臺灣大學
生物環境系統工程學研究所
93
This dissertation proposes a physiologically and bioenergetics based algorithm to relate acute and chronic metal toxicities to the internal effect concentration (IEC) of arsenic (As) in tilapia Oreochromis mossambicus. The relationships among As exposure, uptake, accumulation, and toxicity to tilapia are investigated using toxicokinetic (TK) and toxicodynamic (TD) modeling. A 7-d exposure bioassay reveals that the organ-specific bioconcentration factor (BCF) values of tilapia are all above 1 (1.04 – 3.05), indicating that the tilapia is capable of accumulating waterborne As. The As acute toxicity is analyzed by determining the median external effect concentration (LC50) at different integration times, indicating that 96-h LC50 and LC50(∞) for tilapia are 28.68 (95% CI: 24.92-32.44) and 12.04 µg mL-1, respectively. To determine the mode of action (MOA) governing the As acute toxicity, this study assesses the proposed mechanistics base acute toxicity models, including the critical body residue (CBR) model, the critical area under the curve (CAUC) model, and the recently proposed damage assessment model (DAM). This study test the 3 toxicity models with observed data of tilapia exposed to As, to compare the observed and predicted LC50 and median internal effect concentration (CL,50). Result suggests that the DAM characterizes As acute toxicity well and indicates that the intrinsic MOA of As toxicity might act through the reversible reaction between As and specific receptors in target sites. A physiologically based toxicokinetic (PBTK) model is constructed to elucidate the major mechanisms, accounting for the organ-specific selected accumulation of As in tilapia and then utilize the model to predict the behavior of As in tilapia under different exposure scenarios. This study links kinetically DAM with IEC-based Hill equation model to derive dose-response relationships between equilibrium organ-specific As burdens and mortality effects. Organ-specific dose-response relationships suggest that the gill can be used as a surrogate to assess the As toxicity due to its higher sensibility to toxic effects. To assess As chronic toxicity to tilapia, a bioenergetics-based approach is presented to analyze effects and the MOA of growth inhibition when tilapia are chronically exposed to waterborne As. A 28-d growth bioassay is conducted to quantitatively determine the relationships between As exposures and the magnitudes of growth inhibition. A bioenergetics-based ontogenetic growth model is incorporated with the DEBtox theory to explore the MOA of As growth toxicity. Result shows that the specific growth rates are inversely proportional to As concentrations and are calculated to be 0.76 % d-1 in 0 µg mL-1, 0.54 % d-1 in 1 µg mL-1, 0.26 % d-1 in 2 µg mL-1, and 0.017 % d-1 in 4 µg mL-1, respectively. This study indicates that decreasing of feeding accounts for the As growth inhibition in the case of feeding ad libitum condition. The bioenergetics-based growth model also illustrates the growth trajectories of tilapia in the entire life cycle, suggesting that the maximum biomass of tilapia are 1100.82 g in uncontaminated water, 924.00 g in 1 µg mL-1, 421.51 g in 2 µg mL-1, and 352.13 g in 4 µg mL-1, respectively. The study shows that the proposed physiologically and bioenergetics-based assessment framework successfully links As exposure to TK and TD under varied exposure scenarios. This study also suggests that considering MOAs in ecotoxicology not only improves our understanding of the toxicities of chemicals but also is useful in setting up models and avoiding pitfalls in species- and site-specific environmental risk assessment. This study also supports the suggestion that replacing external concentrations by IECs is a first step toward a measurement for chemical toxicity and can be used to improve the construction of future environmental quality criteria programs, aimed at protecting and restoring the rapidly degrading aquacultural ecosystems.