Physiologically-based toxicokinetic models for toxic metal mixtures: Development and demonstration of a mechanistically consistent framework
A. Sasso, P.G. Georgopoulos
Environmental and Occupational Health Sciences Institute, UMDNJ - R.W. Johnson Medical School and Rutgers University, Piscataway, NJ
Physiologically Based ToxicoKinetic (PBTK) models have become the tools of choice for predicting the fate of environmental contaminants in humans. While several PBTK models have been developed for different environmental chemicals, many of them are not mechanistically consistent. This is especially true for the case of toxic metals, where half-lives in the human body range from a few days (e.g. chromium, arsenic) to a few decades (e.g. lead, cadmium). Several differences in the formulation of these models exist with respect to (a) physiological structure (body tissue volume and blood flow ratios), (b) general modeling assumptions (for transport and transformation of the chemicals within the body), and (c) exposure-relevant activities. These PBTKformulations are in general different depending on the chemical that is being modeled. It is therefore not feasible to perform consistent and simultaneous modeling of multiple contaminants in humans (individuals and populations). However, these contaminants typically exist in multiple media (soil, food, and air) as mixtures, and are known to interact at both the toxicokinetic and toxicodynamic levels in humans. This poster introduces a mechanistically consistent, generalized PBTK model for toxic metals. Preliminary case-studies at both the individual and population level are illustrated.
The present work has been funded by the U.S. Environmental Protection Agency (USEPA – Cooperative Agreement CR-83162501). The viewpoints expressed in this work are solely the responsibility of the authors and do not necessarily reflect the views of USEPA or its contractors.