Paraskevi Papakyriakopoulou is a Post-Doctoral Researcher at the School of Chemical Engineering (National Technical University of Athens) and the Department Pharmacy (National and Kapodistrian University of Athens). She received her pharmacy degree in 2019, and her Doctorate in October 2023, fully funded by the Hellenic Foundation for Research & Innovation. Her PhD research focused on developing and evaluating nasal films for nose-to brain drug delivery systems targeting neurodegenerative diseases, both in vitro and in vivo. She has participated in the Erasmus Traineeship program, first as a recent graduate at the University of Ferrara, and later as a PhD student at Trinity College Dublin. Dr. Papakyriakopoulou has co-authored 23 publications in esteemed peer-reviewed journals. Her research primarily focuses on pharmaceutics, including the development and characterization of novel dosage forms, as well as in pharmacokinetics, and toxicokinetics, particularly in the development of physiologically-based kinetic models. She has presented her work through several poster and oral presentations and has received the Best Abstract Award in the PharmSci360 conference of the American Association of Pharmaceutical Scientists.
A Physiologically-Based Kinetic Model for Inhalation Exposure of Perfluorooctanoic Acid (PFOA) in Rats
Authors: Paraskevi Papakyriakopoulou*, Periklis Tsiros, Haralambos Sarimveis
Affiliation: School of Chemical Engineering, National Technical University of Athens, 157 80 Athens, Greece
*Presenting author
Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals extensively used in industrial applications and consumer products. Due to their persistence in the environment and their tendency to bioaccumulate in the human body without being metabolized or adequately expected, PFAS pose significant health risks. Perfluorooctanoic acid (PFOA) being one of the most studied, has been detected in up to 99% of individuals in the U.S. population and is linked to adverse health effects, including high cholesterol, thyroid disorders, and pregnancy-induced hypertension. While ingestion of contaminated food and water is the primary exposure route, inhalation also contributes to human PFOA intake, particularly in high-exposure populations. Occupational inhalation of PFOA has been associated with lung cancer, which is the leading cause of death among PFAS-exposed workers. In this context, a physiologically based kinetic (PBK) model offer a mechanistic framework for stimulating the absorption, distribution, and excretion of PFOA across various organs and tissues following inhalation. Building on existing models, a comprehensive full-body structure was incorporated, including 15 organ compartments and with 3 to 5 subcompartments each. The model was further refined to include lung-specific parameters, integrating datasets from nose-only and intratracheal exposure experiments. Key parameters, such as upper airway absorption and clearance rates, along with alveolar clearance rates, were calibrated using in vitro data and adjusted for tissue-specific protein binding and transporter activity. The model was validated across multiple doses demonstrating accurate predictions of PFOA concentrations in blood, tissues, and excreta. This work provides a valuable tool for assessing inhalation risks and understanding of PFOA kinetics in the respiratory system.
This work has been supported by the CHIASMA project, which has received funding from the European Union’s Horizon Europe Research and Innovation programme under grant agreement No. 101137613.
