A conceptual framework for modeling aggregate and cumulative exposures to chemicals.

Computer simulation programs have been identified as useful tools for characterizing uncertainty and variability in longitudinal exposures to multiple sources by multiple routes of exposures. This paper provides a conceptual framework for such programs that separates and appropriately models the processes that determine uncertainty, inter- and intraindividual variability, as well as the processes that determine the relationships between the individuals and sources of exposure. The framework is based on a series of four nested loops. These are: the exposure event loop that models the route-specific doses to a person from one or more sources at one point in time; the time step loop that moves a person through time updating the sources and the person's characteristics, the interindividual variation loop that determines the initial characteristics of each person modeled, and finally the uncertainty loop that characterizes the uncertainty from model and parameter uncertainties. This framework provides a flexible and internally consistent approach for the design of simulation software.