Characterization of toxicokinetics and toxicodynamics with linear systems theory: application to lead-associated cognitive decline

Environ Health Perspect. 2001 Apr;109(4):361-8. doi: 10.1289/ehp.01109361.


We present a theoretical approach to analysis of toxicokinetics and toxicodynamics using linear systems theory. In our approach, we define two impulse response functions that characterize the kinetic behavior of an environmental agent in the body and the dynamic time-course behavior of its effect on the body. This approach provides a formalism for understanding the relation among exposure, dose, and cumulative biologically effective dose and for understanding the implications of an effect time-course on cross-sectional and longitudinal data analyses. We use lead-associated cognitive decline as a specific example where the approach may be applied.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cognition Disorders / chemically induced*
  • Cognition Disorders / epidemiology
  • Cross-Sectional Studies
  • Environmental Pollutants / adverse effects*
  • Humans
  • Kinetics
  • Lead / adverse effects*
  • Linear Models
  • Longitudinal Studies
  • Models, Theoretical*


  • Environmental Pollutants
  • Lead