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Development and application of a generalized physiologically-based toxicokinetic model for environmental risk assessment
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Development and application of a generalized physiologically-based toxicokinetic model for environmental risk assessment
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ETD_2268
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http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.000052148
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eng
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theses
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Chemical and Biochemical Engineering
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(authority = ETD-LCSH)
Topic
Biochemical toxicology
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(ID = SBJ-3);
(authority = ETD-LCSH)
Topic
Environmental risk assessment
Subject
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(authority = ETD-LCSH)
Topic
Environmental toxicology
Subject
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(authority = ETD-LCSH)
Topic
Pharmacokinetics
Abstract
This thesis presents the development, evaluation, and application of a generalized toxicokinetic model for mixtures of chemicals. Humans are exposed to mixtures of chemicals that are found together in multiple exposure media (soil, food, and air), and at levels that have been shown to cause adverse effects due to toxic interactions. Although several physiologically based toxicokinetic (PBTK) models exist
for different environmental chemicals, using them in assessing risks to co-occurring contaminants is often impractical.
This is especially true for the case of toxic metals, where half-lives in the human body span days (e.g. arsenic), months (e.g. methylmercury), and decades (e.g. lead, cadmium). Several differences in the formulation of these models exist with respect to (a) physiological structure (e.g. body tissue volumes and blood flow ratios), (b) general modeling assumptions (e.g. for transport and transformation of the chemicals within the body), and (c) exposure-relevant parameters. Since assumptions made for one metal or metal compound can be incompatible with the assumptions made for another metal, current formulations are inadequate for use in assessing health risks from mixtures of toxic metals. Further complications arise when assessing risks of both metals and nonmetals, which also interact at the toxicokinetic and toxicodynamic levels. The issues of consistent representation of physiology and chemical interactions across different classes of chemicals such as mixtures of metals and mixtures of metals and organics are addressed through the development of a Generalized Toxicokinetic Model for Mixtures of chemicals (GTMM).
The GTMM resolves inconsistencies by standardizing the physiology across all models, and by allowing simulations of different models to be done simultaneously. It has been implemented as a set of modules in Matlab and as a user-oriented graphical interface in Matlab-Simulink. The GTMM has been evaluated with multiple existing PBTK models for individual chemicals, and the results demonstrate that the GTMM produces identical results as the original published formulations. Subsequently, the GTMM has been applied to different problems relevant to population risk assessment.
for different environmental chemicals, using them in assessing risks to co-occurring contaminants is often impractical.
This is especially true for the case of toxic metals, where half-lives in the human body span days (e.g. arsenic), months (e.g. methylmercury), and decades (e.g. lead, cadmium). Several differences in the formulation of these models exist with respect to (a) physiological structure (e.g. body tissue volumes and blood flow ratios), (b) general modeling assumptions (e.g. for transport and transformation of the chemicals within the body), and (c) exposure-relevant parameters. Since assumptions made for one metal or metal compound can be incompatible with the assumptions made for another metal, current formulations are inadequate for use in assessing health risks from mixtures of toxic metals. Further complications arise when assessing risks of both metals and nonmetals, which also interact at the toxicokinetic and toxicodynamic levels. The issues of consistent representation of physiology and chemical interactions across different classes of chemicals such as mixtures of metals and mixtures of metals and organics are addressed through the development of a Generalized Toxicokinetic Model for Mixtures of chemicals (GTMM).
The GTMM resolves inconsistencies by standardizing the physiology across all models, and by allowing simulations of different models to be done simultaneously. It has been implemented as a set of modules in Matlab and as a user-oriented graphical interface in Matlab-Simulink. The GTMM has been evaluated with multiple existing PBTK models for individual chemicals, and the results demonstrate that the GTMM produces identical results as the original published formulations. Subsequently, the GTMM has been applied to different problems relevant to population risk assessment.
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electronic resource
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xix, 238 p. : ill.
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Ph.D.
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Includes bibliographical references (p. 209-237)
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by Alan F. Sasso
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Sasso
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Alan F.
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1981-
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Alan F. Sasso
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Georgopoulos
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Panos
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chair
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Panos G Georgopoulos
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Isukapalli
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Sastry
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co-chair
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Sastry S Isukapalli
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Androulakis
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Yannis
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Yannis Androulakis
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Yee
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Roy
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Amit
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Amit Roy
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Rutgers University
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Graduate School - New Brunswick
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2010
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2010-01
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xx
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Rutgers University Electronic Theses and Dissertations
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Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
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doi:10.7282/T3XW4JXP
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ETD doctoral
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Rights
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The author owns the copyright to this work.
Copyright
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Copyright protected
Notice
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Open
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Permission or license
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Sasso
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Alan
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2009-12-01 20:36:09
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Alan Sasso
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Rutgers University. Graduate School - New Brunswick
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Author Agreement License
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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