IOSR Journal of Environmental Science, Toxicology and Food Technology (IOSR-JESTFT) e-ISSN: 2319-2402,p- ISSN: 2319-2399.Volume 11, Issue 6 Ver. I (June. 2017), PP 06-13 www.iosrjournals.org DOI: 10.9790/2402-1106010613 www.iosrjournals.org 6 | Page Development of a Human PBBK Model for Mixtures: Trio Mixture of Mercury, Lead, and Selenium Danjuma D. Maza, Joshua O. Ojo Department of Physics and Engineering Physics, Obafemi Awolowo University, Ile-Ife, Nigeria 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. Keywords : physiologically-based, biokinetic, model, mercury, lead, selenium, interaction I. Introduction In environmental health risk assessment, the internal concentrations of active compounds at their target organs need to be related to the dose to which an animal or human subject has been exposed to [1, 2, 3, 4]. Reason being that, both beneficial and adverse effects produced by a chemical substance, in an animal or human subject, are related to the free concentration of the active chemical agent at the target tissue and not the amount of chemical substance at the site of exposure or absorption. Physiologically-based biokinetic models are quite useful tools, in assessing the internal dose at target organs, for a wide variety of exposure scenarios [5, 1, 6, 7]. Humans are constantly being exposed to a host of toxic environmental chemicals. Due to interaction between components of chemical mixtures, exposure to multiple chemicals may bring about significant modulation of tissue dose of the toxic moiety of one or more of the individual components of the chemical mixture [8, 9, 10]. Consequently, the toxicity of chemical substances become modified as a result of co-exposure to multiple agents in the environment [10]. Mercury (Hg) and lead (Pb) are known toxic elements, while selenium (Se) has been known to mitigate their toxic effect. It is increasingly becoming evident that the toxicity of these toxic heavy metals is associated with their interaction with selenium [11, 12, 13, 14, 15, 16]. Mercury and lead both have very high affinity for selenium, forming insoluble complexes with selenium. When selenium is bound to either lead or mercury, it becomes unavailable to carry out its essential functions. Because the complexes formed are insoluble, the retention of these elements in various tissues are affected, altering their partition coefficients in the respective organs [8]. The concentration of the elements in the venous blood, , exiting a given tissue, T, will be modified as: (1) where is the modification factor for the partition coefficient, and are the tissue concentration and partition coefficient. This leads to modifications in the mass balance ordinary differential equations. Modeling the interactions was predicated on the fact that both mercury and lead have very high affinity ( ) for selenium [12, 17, 13, 11]. Furthermore, it was assumed that selenium views mercury and lead as identical elements because of the similarity in their mode of interaction with it. Additionally, it was assumed that there is no interaction between mercury and lead. In a study undertaken by Maza and Ojo [18], models for the binary mixtures of Hg/Se and Pb/Se were developed to provide a platform for viewing the interaction