Graduation Year

2005

Document Type

Thesis

Degree

M.S.P.H.

Degree Granting Department

Public Health

Major Professor

yiliang zhu.

Keywords

Dose-response, Biphasic, Neurotoxicity, Risk, Toxicology

Abstract

In collaboration with the United States Environmental Protection Agency (USEPA), the University of South Florida Health Risk Methodology Group has developed dose-time-response models to characterize neurobehavioral response to chemical exposure. The application of dose-time-response models to neurobehavioral screening tests on laboratory animals allows for benchmark dose estimation to establish exposure limits in environmental risk assessment. This thesis has advanced dose-time-response modeling by generalizing a published toxico diffusion model to allow for dose dependent time of peak effects. To accomplish this, a biphasic model was developed which adopted the effect compartment model paradigm used in pharmacokinetics/pharmacodynamics to estimate a distributional rate constant to account for dose related variation in the time of peak effect.

The biphasic model was able to describe dose-dependent time of peak effects as observed in the data on acute exposure to parathion and adequately predicted the observed response. However, the experimental design appeared insufficient in statistical power to confirm statistical significance for each parameter of interest. Motivated by the question of what design requirement might be necessary to validate the biphasic model, Monte Carlo simulation was adopted. Simulations were performed to assess the efficacy and efficiency of various experimental designs for detecting and evaluating some critical characteristics of the biphasic model, including the TOPE.

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