Development and evaluation of a physiologically-based kinetic model for the transfer of lead in lactating Nigerian women with high and low exposure to lead

Abstract

This study aimed to develop a physiologically-based kinetic model for lead and to predict the kinetic behavior of lead in lactating mothers with the model under different scenarios. The model consisted of the following compartments: the lungs and the digestive tract through which lead enters the systemic circulation, the blood, the cortical bone, the trabecular bone, the soft tissues, the breastmilk and urine. Maple 13 was used to solve the generated model equations numerically (taking into account the mass balance principle). The model was used to simulate tissue lead concentrations in lactating mothers. Evaluation of the predicted concentrations was carried out using experimental data of 27 lactating mothers from Zamfara gold mines (high exposure) and 50 mothers from Ile-Ife (low exposure), both in Nigeria. The model was further used to study how various exposure scenarios such as intermittent exposure, massive medication, low medication, physiological changes (such as pregnancy) influence the levels of lead in key body compartments of female subjects. For massively chelated subjects, blood lead level dropped to 58 μg/dl from 274 μg/dl while milk lead level was reduced to 24 μg/dl from 81 μg/dl. For subjects with low medication, the milk lead level dropped to 154 μg/dl from 274 μg/dl while the milk lead level reduced to 58 μg/dl from 81 μg/dl. The result of the model developed showed that turnover of lead from bone to blood was more in lactation (63%) than in pregnancy (26%). With appropriate values for individual body height and body weight, the simulation results of the model  developed in this study were in 2 agreement with the blood experimental data in both Zamfara (χ =0.0056, r=0.557 at 0.01 significance level) and 2 Ile-Ife (χ = 0.0086, r=0.7851 at 0.01 significance level).The physiologically based kinetic model  developed was an effective approach in predicting tissue lead levels in adult female subjects and also intakes in their breastfed infants based on exposure lead data from mothers.

Keywords: PBK Model, Lead, Blood, Breastmilk, Lactating Mothers