Development of a Human PBBK Model for Mixtures: Trio Mixture of Mercury, Lead, and Selenium

Abstract

A physiologically-based biokinetic (PBBK) model has been developed for predicting simultaneously the ADME properties of lead, mercury, and selenium in a number of target tissues of humans. Independent models for mercury, lead and selenium which were developed in a previous study undertaken by us were integrated into a single model for the mixture of these elements. Oral doses were presented in μmol/kg/day, while tissue concentrations were in μmol/kg. The integration was based on the fact that interaction among these elements affects their bioaccumulation in the respective tissues, resulting in alterations to their partition coefficients. Combined oral doses of mercury and lead were categorized as either low or high, while selenium doses were categorized as either low, adequate or high. With the combined dose of mercury and lead categorized as low, and selenium dose also categorized as low, the concentration of mercury and lead in the liver, kidney, brain, richly perfused tissues, and slowly perfused tissues were modulated by factors of 2.01, 0.91, 1.5, 0.91, and 0.90, respectively, while the concentration of selenium in these tissues were modulated by factors of 0.03, 0.21, 0.89, 0.75, and 0.75, respectively. On the other hand, with the combined dose of mercury and lead categorized as high and selenium dose categorized as low, the concentration of mercury and lead in these tissues were modulated by factors of 1.51, 0.68, 1.28, 1.45, and 1.45, respectively, while that of selenium were modified by factors of 0.05, 0.30, 0.45, 0.60, and 0.60, respectively. With adequate selenium intake and combined dose of mercury and lead categorized as high, the concentration of mercury and lead in the various tissues were not modulated, while the concentration of selenium in the liver, kidney, brain, richly perfused tissues, and slowly perfused tissues were modulated by factors of 0.82, 2.89, 0.96, 0.64, and 0.64, respectively.