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Evaluating the influence of half-life, milk:plasma partition coefficient, and volume of distribution on lactational exposure to chemicals in children

Author:
Verner, Marc-André, Plouffe, Laurence, Kieskamp, Kyra K., Rodríguez-Leal, Inés, Marchitti, Satori A.
Source:
Environment international 2017 v.102 pp. 223-229
ISSN:
0160-4120
Subject:
Monte Carlo method, biological half-life, breast milk, children, decision support systems, equations, half life, lactation, regression analysis, simulation models, women
Abstract:
Women are exposed to multiple environmental chemicals, many of which are known to transfer to breast milk during lactation. However, little is known about the influence of the different chemical-specific pharmacokinetic parameters on children's lactational dose. Our objective was to develop a generic pharmacokinetic model and subsequently quantify the influence of three chemical-specific parameters (biological half-life, milk:plasma partition coefficient, and volume of distribution) on lactational exposure to chemicals and resulting plasma levels in children. We developed a two-compartment pharmacokinetic model to simulate lifetime maternal exposure, placental transfer, and lactational exposure to the child. We performed 10,000 Monte Carlo simulations where half-life, milk:plasma partition coefficient, and volume of distribution were varied. Children's dose and plasma levels were compared to their mother's by calculating child:mother dose ratios and plasma level ratios. We then evaluated the association between the three chemical-specific pharmacokinetic parameters and child:mother dose and level ratios through linear regression and decision trees. Our analyses revealed that half-life was the most influential parameter on children's lactational dose and plasma concentrations, followed by milk:plasma partition coefficient and volume of distribution. In bivariate regression analyses, half-life explained 72% of child:mother dose ratios and 53% of child:mother level ratios. Decision trees aiming to identify chemicals with high potential for lactational exposure (ratio>1) had an accuracy of 89% for child:mother dose ratios and 84% for child:mother level ratios. Our study showed the relative importance of half-life, milk:plasma partition coefficient, and volume of distribution on children's lactational exposure. Developed equations and decision trees will enable the rapid identification of chemicals with a high potential for lactational exposure.