Advancing PFAS risk assessment: Integrative approaches using agent-based modelling and physiologically-based kinetic for environmental and health safety

Martina Iulini; Giulia Russo; Elena Crispino; Alicia Paini; Styliani Fragki; Emanuela Corsini; Francesco Pappalardo

doi:10.1016/j.csbj.2024.06.036

Advancing PFAS risk assessment: Integrative approaches using agent-based modelling and physiologically-based kinetic for environmental and health safety

Comput Struct Biotechnol J. 2024 Jul 1:23:2763-2778. doi: 10.1016/j.csbj.2024.06.036. eCollection 2024 Dec.

Authors

Martina Iulini¹, Giulia Russo², Elena Crispino³, Alicia Paini⁴, Styliani Fragki⁴, Emanuela Corsini¹, Francesco Pappalardo²

Affiliations

¹ Università degli Studi di Milano, Department of Pharmacology and Biomolecular Sciences 'Rodolfo Paoletti', Milan, Italy.
² University of Catania, Department of Drug and Health Sciences, Italy.
³ University of Catania, Department of Biomedical and Biotechnological Sciences, Italy.
⁴ esqLABS GmbH, Saterland, Germany.

Abstract

Per- and polyfluoroalkyl substances (PFAS), ubiquitous in a myriad of consumer and industrial products, and depending on the doses of exposure represent a hazard to both environmental and public health, owing to their persistent, mobile, and bio accumulative properties. These substances exhibit long half-lives in humans and can induce potential immunotoxic effects at low exposure levels, sparking growing concerns. While the European Food Safety Authority (EFSA) has assessed the risk to human health related to the presence of PFAS in food, in which a reduced antibody response to vaccination in infants was considered as the most critical human health effect, a comprehensive grasp of the molecular mechanisms spearheading PFAS-induced immunotoxicity is yet to be attained. Leveraging modern computational tools, including the Agent-Based Model (ABM) Universal Immune System Simulator (UISS) and Physiologically Based Kinetic (PBK) models, a deeper insight into the complex mechanisms of PFAS was sought. The adapted UISS serves as a vital tool in chemical risk assessments, simulating the host immune system's reactions to diverse stimuli and monitoring biological entities within specific adverse health contexts. In tandem, PBK models unravelling PFAS' biokinetics within the body i.e. absorption, distribution, metabolism, and elimination, facilitating the development of time-concentration profiles from birth to 75 years at varied dosage levels, thereby enhancing UISS-TOX's predictive abilities. The integrated use of these computational frameworks shows promises in leveraging new scientific evidence to support risk assessments of PFAS. This innovative approach not only allowed to bridge existing data gaps but also unveiled complex mechanisms and the identification of unanticipated dynamics, potentially guiding more informed risk assessments, regulatory decisions, and associated risk mitigations measures for the future.

Keywords: Agent-based modeling; Immunotoxicity; Per- and polyfluoroalkyl substances (PFAS); Physiologically based kinetic modeling; Risk assessment.