The Cochlea as a Specialty Compartment: Toxicokinetic Modeling of Solvent DistributionEPA Grant Number: U914755
Title: The Cochlea as a Specialty Compartment: Toxicokinetic Modeling of Solvent Distribution
Investigators: Pearce, Terri A.
Institution: University of Oklahoma
EPA Project Officer: Klieforth, Barbara I
Project Period: January 1, 1995 through July 9, 1999
Project Amount: $102,000
RFA: STAR Graduate Fellowships (1995) Recipients Lists
Research Category: Fellowship - Health , Health Effects , Academic Fellowships
The objective of this research project is to aid risk assessment by contributing to our understanding of solvent ototoxicity.
Classical toxicological methods do not offer all of the tools necessary to allow for rapid screening of ototoxicants. Consequently, the information needs of the scientific and regulatory communities, along with those of the general public, may not be fully met. To meet these needs, toxicologists are expected to adapt classical methods to emerging technologies. One of those emerging technologies is the ability to perform toxicokinetic modeling rapidly and easily. Models can offer initial information, which may be verified through classical laboratory methods. This research will seek to adapt one of the existing toxicokinetic modeling software programs to a specialty compartment; specifically, the cochlea. It will examine existing models for their ability to predict solvent concentrations found there. Toluene and trichloroethylene will be used in this study, as both have been implicated in ototoxicity.
Current estimates of cochlear concentration, either through models or through laboratory exposures, assume that solvent concentrations found in the brain are representative of concentrations in other neural tissues including the cochlea. Although this assumption may be accurate, it has not been validated. This research project will seek to address this issue. The models will be compared according to predicted concentrations of solvent in the brain and how those predictions relate to experimental values from the literature. The validity of the model then will be challenged experimentally by injecting animals with radiolabelled solvent. The concentrations found in the cochlea as well as brain, blood, and liver will be determined, and the measured values will be compared to those predicted by the model. This research project will substantiate whether it is appropriate to assume that concentrations in the brain mirror those in the cochlea. The final component of the research project will be to determine whether noise influences the distribution of solvent in the cochlea through simultaneous solvent and noise exposure.