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Jonathan M. Links,¹ Brian S. Schwartz,^1,2 David Simon,² Karen Bandeen-Roche,³ and Walter F. Stewart²

Departments of ¹Environmental Health Sciences, ²Epidemiology, and ³Biostatistics, The Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland, USA

Abstract

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. Key words: bone lead, exposure assessment, linear systems model, toxicodynamics, toxicokinetics. Environ Health Perspect 109:361-368 (2001) . [Online 16 March 2001]

http://ehpnet1.niehs.nih.gov/docs/2001/109p361-368links/ abstract.html

Address correspondence to J.M. Links, Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, 615 North Wolfe Street, Baltimore, MD 21205-2179 USA. Telephone: (410) 955-9622. Fax: (410) 955-6222. E-mail: jlinks@jhsph.edu

We thank J. Prince and A. Todd for helpful discussions and the reviewers for important clarifying comments.

This research was supported in part by NIH grants R01 AG10785 from the National Institute on Aging and P30 ES03819 from the National Institute of Environmental Health Sciences.

Received 22 September 2000 ; accepted 25 October 2000.