Treffer: An integrated in vitro and in silico testing strategy applied to PFAS inhibition of antibody production to define a tolerable daily intake.

Title:
An integrated in vitro and in silico testing strategy applied to PFAS inhibition of antibody production to define a tolerable daily intake.
Authors:
Iulini M; Laboratory of Toxicology and Risk Assessment, Department of Pharmacological and Biomolecular Sciences 'Rodolfo Paoletti', Università degli Studi di Milano, Milan, Italy. Electronic address: martina.iulini@unimi.it., Janssen AWF; Wageningen Food Safety Research (WFSR), Wageningen, the Netherlands., Beekmann K; Wageningen Food Safety Research (WFSR), Wageningen, the Netherlands., Russo G; Department of Drug and Health Sciences, Università degli Studi di Catania, Italy., Pappalardo F; Department of Drug and Health Sciences, Università degli Studi di Catania, Italy., Fragki S; ESQlabsGmbH, Saterland 26683, Germany., Paini A; ESQlabsGmbH, Saterland 26683, Germany., Corsini E; Laboratory of Toxicology and Risk Assessment, Department of Pharmacological and Biomolecular Sciences 'Rodolfo Paoletti', Università degli Studi di Milano, Milan, Italy.
Source:
Toxicology letters [Toxicol Lett] 2026 Feb; Vol. 416, pp. 111817. Date of Electronic Publication: 2026 Jan 03.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7709027 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-3169 (Electronic) Linking ISSN: 03784274 NLM ISO Abbreviation: Toxicol Lett Subsets: MEDLINE
Imprint Name(s):
Publication: Amsterdam : Elsevier
Original Publication: Amsterdam, Elsevier/North Holland.
MeSH Terms:
Computer Simulation* , Fluorocarbons*/toxicity , Fluorocarbons*/pharmacokinetics , Leukocytes, Mononuclear*/drug effects , Leukocytes, Mononuclear*/immunology , Antibody Formation*/drug effects , Environmental Pollutants*/toxicity, Humans ; Risk Assessment
Contributed Indexing:
Keywords: Antibody production; Immunotoxicology; In vitro and in silico models; Next generation risk assessment; Per- and polyfluoroalkyl substances
Substance Nomenclature:
0 (Fluorocarbons)
0 (Environmental Pollutants)
Entry Date(s):
Date Created: 20260106 Date Completed: 20260130 Latest Revision: 20260130
Update Code:
20260131
DOI:
10.1016/j.toxlet.2025.111817
PMID:
41490601
Database:
MEDLINE

Weitere Informationen

Per- and polyfluoroalkyl substances (PFAS) are widely used chemicals known for their persistence, bioaccumulation, and adverse health effects, particularly on the immune system. Epidemiological studies link PFAS exposure to immunosuppression, with increased infection susceptibility and reduced vaccine efficacy. In this paper, we describe the workflow we used to establish an integrated testing strategy (ITS) combining in vitro and in silico methods to model PFAS inhibition of antibody production and to define a tolerable daily intake. This strategy was based on data generated within an EFSA-sponsored project. Using human peripheral blood mononuclear cells, the effects of PFAS on antibody production were assessed. Mathematical models were then applied to determine PFAS free concentrations in vitro, while Physiologically Based Kinetics (PBK) modeling enabled quantitative in vitro to in vivo extrapolation (QIVIVE) to translate in vitro effects into external doses. In addition, the Universal Immune System Simulator was used to predict immune-related outcomes and threshold doses for sensitive populations. Following this strategy, we were able to demonstrate that the oral equivalent effect doses derived through QIVIVE were similar to, or lower than, the tolerable weekly intake established by EFSA for PFAS, indicating that our approach is conservative. We demonstrate the possibility of using alternative methods for studying PFAS toxicity, offering insights into their dynamics and kinetics without animal testing. The strategy provides a promising framework for assessing other chemicals, advancing toxicology toward more human-relevant and ethical practices.
(Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved.)

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.