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Physiologically Based Toxicokinetic (PBTK) Model for Inhalation Exposure to Benzene and Its Engineering Applications

Title: A Physiologically Based Toxicokinetic (PBTK) Model for Inhalation Exposure to Benzene and Its Engineering Applications.
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Name(s): Kulkarni, Tara Aniket, author
Dzurik, Andrew, professor directing dissertation
Arora, Krishna, outside committee member
Kolta, Malak, committee member
Leszczynska, Danuta, committee member
Hilton, Amy Chan, committee member
Department of Civil and Environmental Engineering, degree granting department
Florida State University, degree granting institution
Type of Resource: text
Genre: Text
Issuance: monographic
Date Issued: 2004
Publisher: Florida State University
Place of Publication: Tallahassee, Florida
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Physiologically Based Parmacokinetic/Toxicokinetic (PBPK/TK) Models are commonly used in the pharmaceutical and toxicological sciences to understand the fate and disposition of drugs in the human body. However, they are not being applied in environmental engineering studies involving risk, except in some health risk assessment studies. The risk posed by the adverse effects of a xenobiotic on the human body can be quantified using PBPK/TK models and such numbers can be used in engineering situations such as determining clean up levels at remediation sites, locating hazardous waste facilities and installing pollution control and monitoring devices. Thus the PBPK/TK modeling can serve as an appropriate tool in global initiatives such as Risk Based Corrective Action (RBCA). This study presents two areas of new and contributory research. The first is a toxicological model for benzene and its major metabolites considering different doses and forms (continuous and intermittent) of inhalation exposure in male and female subjects of the human population. This model considers the bone marrow as a separate compartment and uses an extended version of the Michaelis- Menten kinetics for enzymes, both areas of study, not strongly addressed before. The results of this part of the study reveal that PBPK/TK models can successfully simulate intermittent exposures, which had not been done before. The benzene concentration levels are not significantly different in male and female exposures. The addition of the bone marrow as a separate compartment is recommended in all benzene models. The sensitivity analysis based on the Monte Carlo technique indicate that most of the rate constants tested, that are involved in the metabolic processes are stable; 2 are highly sensitive. The partition coefficient of benzene for the fat compartment is somewhat stable, but the model probably over-predicts the benzene concentrations in the fat compartment. The second part of the study is to determine the possible use of PBPK/TK models in environmental engineering studies. Verbal communication from personnel of the Florida Department of Environmental Protection encouraged the theory that the model developed in this study can be potentially used in RBCA aspects of environmental engineering. So, an environmental engineering case study was presented to demonstrate its use as a screening tool at a petroleum contaminated site. Benzene concentration levels are estimated in male workers, at the site working on a remediation project for 3 months and getting exposed to 8 hours/day, 5days/week of continuous benzene exposure. An example on the potential use of the model in air pollution engineering problems is also presented. The results from this portion of the study as well as personal communication with FDEP personnel indicate that the PBPK/TK model developed in this study will benefit environmental engineering studies.
Identifier: FSU_migr_etd-2971 (IID)
Submitted Note: A Dissertation submitted to the Department of Civil and Environmental Engineering in partial fulfillment of the requirements for the degree of Doctor of Philosophy.
Degree Awarded: Spring Semester, 2004.
Date of Defense: April 02, 2004.
Keywords: Benzene, PBTK, Model, Toxicokinetic, Engineering Application, Inhalation
Bibliography Note: Includes bibliographical references.
Advisory Committee: Andrew Dzurik, Professor Directing Dissertation; Krishna Arora, Outside Committee Member; Malak Kolta, Committee Member; Danuta Leszczynska, Committee Member; Amy Chan Hilton, Committee Member.
Subject(s): Civil engineering
Environmental engineering
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_migr_etd-2971
Owner Institution: FSU

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Kulkarni, T. A. (2004). A Physiologically Based Toxicokinetic (PBTK) Model for Inhalation Exposure to Benzene and Its Engineering Applications. Retrieved from http://purl.flvc.org/fsu/fd/FSU_migr_etd-2971