Generic Pharmacokinetic Models for Mother-to-Offspring Transfer of Environmental Chemicals
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In developing human health risk assessments, it is important to consider pregnant women, developing fetuses, and nursing children because chemical exposures experienced by these groups can lead to special types of adverse health outcomes (e.g., developmental effects) that do not typically arise in non-pregnant adults that experience similar exposures. Pharmacokinetic (PK) models, which are frequently used in chemical risk assessments, provide a means for estimating internal dose metrics from applied doses or environmental exposures based on mathematical descriptions of absorption, distribution, metabolism, and excretion (ADME). In addition to the ADME mechanisms commonly represented in adult PK models, PK models for pregnancy (and gestation) and the early postnatal period may include mathematical descriptions of transplacental and lactational transfer of chemicals from mothers to their offspring. We have developed two distinct PK models for human perinatal exposure scenarios that include mother-to-offspring transfer. The first model allows for simulations that quantify bioaccumulation of lipophilic persistent environmental chemicals (LPECs) in rats, mice, and humans, as well as transplacental and lactational mother-to-offspring transfer. The second is a physiologically based pharmacokinetic (PBPK) model that describes ADME in a pregnant human mother and her developing fetus during gestation. Both models are generic in the sense that they can be parameterized for many chemicals. We will provide details of the two generic PK models for mother-to-offspring transfer of chemicals, including a description of steps we took to develop and evaluate these models and a summary of their limitations. Then, we will provide examples of risk assessment applications of the models.