Utility of Biochemical Systems Theory for the Analysis of Metabolic Effects from Low-Dose Chemical Exposure

Adverse health outcomes from exposure to chemical agents are of increasing interest in human and ecological risk assessment and require the development of new analytical methods. Such methods must be able to capture the essence of integrated networks of biochemical pathways in a mathematically feasible fashion. Over the past three decades, Biochemical Systems Theory has been successfully applied to numerous biological systems. It is suggested here that S-system models derived from BST can provide the means for assessing chemical exposures and their effects at the metabolic level. This article briefly reviews essential concepts of S-systems and provides generic examples of chemical exposure scenarios. S-system models can be considered mechanistic, since their components are measurable quantities (e.g., concentrations, fluxes, enzyme activities, and rates). As dynamic models, they can be used to assess immediate and long-term metabolic responses to environmental stimuli. Direct mathematical analysis for low exposures leads to simple dose-response relationships, which have the form of power-law functions. Thus, if the S-system model yields an appropriate description of chemical exposure and its metabolic effects, the dose-response relationship for low exposures is linear in logarithmic coordinates. This result includes as a special case the standard linear relationship in Cartesian coordinates with zero intercept.