Development of human PBBK models for mixtures: Binary mixtures of mercury/ selenium, and lead/selenium

Abstract

Physiologically-based biokinetic models have been developed for predicting  simultaneously the Absorption, Distribution, Metabolism and Elimination (ADME) properties of lead (Pb) and selenium (Se), and mercury (Hg) and selenium in a number of target tissues of humans. This was done for three population groups, namely, women of child bearing age (pregnant, lactating and non-pregnant-non-lactating), fetus, and infants/children (0 -5 years of age). This was with a view to applying the model to environmental health risk assessment. For each of the elements, three independent models were developed for each population group, making a total of 9 models. These models were able to simulate reasonably the results of controlled experiments obtained from literature. The models were then integrated into binary pairs of Hg/Se and Pb/Se to facilitate viewing the interaction between mercury and selenium, and lead and selenium. Interaction among these elements affected the bioaccumulation of these elements in the respective tissues, thus, altering their partition coefficients. Alterations in the partition coefficients of these elements were modelled by incorporating in the models modification factors derived from the result of the study conducted by Ralston and  Cohorts in 2008 on rats. This enabled the integrated models to simulate simultaneously the modulated concentration profiles due to the interaction of these elements. The modulated tissue concentrations were then used in a hypothetical health risk  assessment of these elements. The results showed that until selenium intake was adequate or high, even low doses of mercury or lead could be considered as health risk. The results further showed that for the infant child, unless selenium intake was high, the brain was quite susceptible to mercury intoxication, even at low doses.

Keyword: Human PBBK Models, Binary Mixtures, Mercury/Selenium, Lead/Selenium.