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OLS Field Name OLS Field Data
Main Title On the incorporation of biokinetic and mechanistic data in modeling for risk assessment /
Author Clewell, Harvey J.
Publisher Utrecht University,
Year Published 2007
OCLC Number 823937589
ISBN 9789039344774; 9039344779
Subjects Hazardous substances--Risk assessment. ; Environmental chemistry. ; Environmental risk assessment.
Internet Access
Description Access URL
Item Resolution URL http://igitur-archive.library.uu.nl/dissertations/2007-0712-201925/UUindex.html
Holdings
Library Call Number Additional Info Location Last
Modified
Checkout
Status
EKBM  TD196.C45C64 2007 Research Triangle Park Library/RTP, NC 09/08/2014
ELBM  TD196.C45C64 2007 AWBERC Library/Cincinnati,OH 01/14/2013
Collation 472 p. : ill., charts ; 24 cm.
Notes
Includes bibliographical references.
Contents Notes
The goal of the studies described in this thesis was to foster the increased use of emerging scientific information and innovative methods in chemical risk assessments, in order to assure the protection of public health while limiting the economic and social consequences of over-regulation. The first part of the thesis presents three studies that were performed to demonstrate approaches for incorporating biokinetic and mechanistic data and mathematical modeling in risk assessment, focusing on mode of action evaluation, physiologically based biokinetic (PBBK) modeling, and benchmark dose-response (BMD) modeling. The second part of the thesis documents three studies that were performed to show the ability of PBBK modeling to describe the interaction between chemical-specific properties, physiology, and age-dependent biochemical processes and the resulting variability in risks across individuals in a population at different ages. The final part of the thesis describes three studies that attempted to make optimal use of available biokinetic and mechanistic data in cancer risk assessments for vinyl chloride, trichloroethylene, and perchloroethylene using the three methodologies discussed in the first section of the thesis. Overall, the research described in this thesis demonstrates that the use of mode-of-action evaluation, PBBK modeling, and quantitative dose-response modeling greatly increases the opportunity for the use of biokinetic and mechanistic data in risk assessment. The resulting risk assessment approaches are more appropriately tailored to the specific chemical and are likely to provide a more accurate assessment of the potential hazards associated with human exposures. The studies in this thesis also demonstrate that the application of PBBK models in risk assessment demands well-formulated statements about the chemical mode of action. It is this requirement for an explicit, mechanistic hypothesis that gives biologically motivated models their power, but at t