JSM 2004 - Toronto

Abstract #301885

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Activity Number: 81
Type: Contributed
Date/Time: Monday, August 9, 2004 : 8:30 AM to 10:20 AM
Sponsor: Section on Risk Analysis
Abstract - #301885
Title: A Nonlinear Pharmacokinetic-Weibull Model for Low-risk Dose Estimation for Carcinogenic Agents
Author(s): Abdul S. Al-Khalidi*+
Companies: Insurance Bureau of Canada
Address: 2235 Sheppard Ave. East, Toronto, ON, M2J 5B5, Canada
Keywords: low-risk dose ; renewal Weibull process ; tolerance ; pharmacokinetic model
Abstract:

This paper introduces a statistical model to estimate low risk doses of carcinogenic substances from data in which time to tumor onsets are recorded or estimated. The low-risk dose estimator is derived from a parametric probability distribution for the time to tumor onset to provide exposure duration effect, as well as dose levels. The derived probability distribution for the tumor onset time assumes: (1) the effective dose is a nonlinear pharmacokinetic transform of the exposed (or administered) dose; and (2) the probabilistic model underlying the waiting time of occurrence of a tumor is a Renewal Weibull Process. In the area of toxicology and environmental health, the damaging effects of environmental chemical (such as gaseous toxins) or other stimuli are often studied in animal and microbial systems. Data from such experiments will be analyzed via the model developed in this work. The literature on the topic is full with various models, using different assumptions. Most of these models consider the administered dose as effective dose, the derived models are built on this basis, and the low-risk doses are estimated using extrapolations.

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