Citation:

Schlosser, P., D. Kapraun, T. Zurlinden, AND M. Verner. Predicted Accumulation of Persistent Compounds Across Generations. 2022 SOT Annual Meeting, San Diego, CA, March 27 - 31, 2022.

Impact/Purpose:

Describe results of pharmacokinetic modeling of PFDA in humans for developmental exposure, which have general implications for long-term biopersistent compounds in general.

Description:

Persistent organic pollutants like long-chain perfluoroalkyl substances can bioaccumulate over a significant part of a woman’s lifetime and then be transferred to offspring in utero and via breastfeeding. We used computational simulations to explore how perinatal exposures impact long-term body burden of a bioaccumulative substance. A pharmacokinetic model was adapted from Verner et al. (2016) to evaluate bioaccumulative dosimetry in female rodents and humans and their offspring while accounting for growth and in-utero and lactational transfer. For example, the half-life of perfluorodecanoic acid (PFDA) in women was estimated to be 6.7 y with menstrual blood loss and 7.9 y without. Assuming a constant continuous exposure, whole-body PFDA concentration was calculated from a woman’s birth through pregnancy (beginning at age 24.25 y; i.e., 25 years and 3 months), childbirth (at age 25), and exclusive breast-feeding of her daughter for 1 y. The daughter was then assumed to have the same constant continuous exposure and to follow the same life cycle. A simulated woman born with zero body burden is only predicted to reach 74% of steady-state concentration by age 24.25 y. Her simulated daughter was then born with an elevated concentration and received a large amount of PFDA from breastfeeding such that her whole-body concentration during the first several years of life exceeded the highest concentration calculated for the mother. Continuing at the same exposure rate, the daughter’s body burden reaches 85% of steady-state at 24.25 y, indicating modest cross-generational accumulation. Thus, a woman’s body burden of a bioaccumulative substance is likely to be somewhat lower than the steady-state level in early adulthood, but it can be influenced by her mother’s lifetime exposure, even for a substance with a half-life of only 7-8 y. While there are significant health benefits to breast-feeding that likely offset the exposure, the predicted concentration spike for the daughter is concerning. Since the concentration in a young adult woman depends on her childhood exposure, including what is transferred to her from her mother, the full effect of multigeneration exposure should be included when estimating safe exposure levels for children.

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