Development of a human Physiologically Based Pharmacokinetic (PBPK) Toolkit for environmental pollutants

Abstract

Physiologically Based Pharmacokinetic (PBPK) models can be used to determine the internal dose and strengthen exposure assessment. Many PBPK models are available, but they are not easily accessible for field use. The Agency for Toxic Substances and Disease Registry (ATSDR) has conducted translational research to develop a human PBPK model toolkit by recoding published PBPK models. This toolkit, when fully developed, will provide a platform that consists of a series of priority PBPK models of environmental pollutants. Presented here is work on recoded PBPK models for volatile organic compounds (VOCs) and metals. Good agreement was generally obtained between the original and the recoded models. This toolkit will be available for ATSDR scientists and public health assessors to perform simulations of exposures from contaminated environmental media at sites of concern and to help interpret biomonitoring data. It can be used as screening tools that can provide useful information for the protection of the public.

Keywords: National Health and Nutrition Examination Survey (NHANES); PBPK; VOCs; metals; toxicokinetic; volatile organic compounds.

Figure 1

Trichloroethylene (TCE) blood concentrations (●) measured over time, following a 4 h, 50 ppm TCE inhalation exposure (Fisher et al. 1998 [22]). The original simulation (---) and our generic VOCs model simulation (—) are also shown.

Figure 2

Total As, monomethyl arsenic (MMA), and dimethylarsenic (DMA) cumulative urinary excretion in human volunteers exposed to 100 μg As in the form of sodium arsenate (panel a) and sodium arsenite (panel b). Our recoded model simulation (Left, solid line) versus the reworked original simulation by El-Masri and Kenyon, 2008 [12] (Right, solid line).