Development of edible sorbent therapies to mitigate dietary exposures to per- and polyfluoroalkyl substances (PFAS)

点击翻译按钮获取中文摘要

ABSTRACT Per- and polyfluoroalkyl substances (PFAS), also known as “forever chemicals”, are emerging contaminants of concern due to their prevalence (in 99% of blood samples in the U.S.), long half-life, and adverse health effects in humans. PFAS can be released, mobilized, and redistributed in the environment during emergencies such as fires, industrial incidents, hurricanes, and flooding, thus enhancing human exposures and health effects. A major challenge associated with these emergencies is protecting vulnerable populations including first responders, frontline personnel, and communities at the impacted sites. There is a critical need for the development of practical strategies to minimize dietary exposures to PFAS from drinking water and food, which account for 90% of human exposures. Mitigation strategies using edible sorbents in the diet are safe for human consumption. The long-term goal is to establish therapeutic sorbent interventions that will reduce oral and inhalation exposures to complex environmental contaminants and microbes. The overall objective of this project is to develop edible, multicomponent sorbents that will effectively reduce PFAS exposures from the diet. In this project, six representative PFAS and their mixtures have been selected for complementary in vitro, in silico, and in vivo studies. In Aim 1, multicomponent sorbents including processed and nutrient-amended clays will be derived from materials that are naturally occurring, or generally recognized as safe. The in vitro adsorption studies will be conducted in simulated gastrointestinal tract models to characterize surface interactions. The detoxification efficacy of sorbent treatment will be validated in mammalian cell models and a living organism (Hydra vulgaris). In Aim 2, molecular dynamics (MD) simulations, energetic analysis, minimalistic MD simulations, and data-driven models will be used to study complex systems containing mixtures of PFAS and multicomponent sorbents. Computational studies will validate sorption mechanisms and thermodynamics and integrate with Aim 1 for sorbent selection and characterization. In Aim 3, the efficacy and safety of selected sorbents will be tested in vivo. Male and pregnant female rats will be exposed to PFAS and sorbents will be included in the diet at varying doses for 3 weeks. The 3 sorbents that most effectively reduce the PFAS bioavailability and show no interference with nutrients will be included in a 6-month safety study. Parameters to be determined include 1) PFAS bioavailability in blood, urine, and breast milk, 2) nutrient levels, 3) body weight, relative organ-to-body weight, and infant birth weight, 4) feed conversion efficiency, and 5) clinical blood biochemistry. It is expected that therapeutic sorbents developed in this research will be field-practical and easily delivered orally to neutralize PFAS mixtures from dietary exposures to protect and treat vulnerable populations during emergencies.