Translatability and transferability of in silico models: context of use switching to predict the effects of environmental chemicals on the immune system

Immunotoxicity hazard identification of chemicals aims to evaluate the potential for unintended effects of chemical exposure on the immune system. Perfluorinated alkylated substances (PFAS), such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), are persistent, globally disseminated environmental contaminants known to be immunotoxic. Elevated PFAS exposure is associated with lower antibody responses to vaccinations in children and in adults. In addition, some studies reported a correlation between PFAS levels in the body and lower resistance to disease or an increased risk of infections. In this context, modelling and simulation platforms could be used to simulate the human immune system with the aim to evaluate the adverse effects that immunotoxicants may have. Here, we show the conditions under which a mathematical model developed for one purpose and application (e.g., in the pharmaceutical domain) can be successfully translated and transferred to another (e.g., in the chemicals domain) without undergoing significant adaptation. In particular, we demonstrate that the Universal Immune System Simulator was capable to simulate the effects of PFAS on the immune system, introducing entities and new interactions that are biologically involved in the phenomenon. This illustrates a potentially exploitable pathway for assessing immunotoxicity using a computational model.

PAPPALARDO Francesco;  RUSSO Giulia;  CORSINI Emanuela;  PAINI Alicia;  WORTH Andrew; 

2022-04-20

ELSEVIER

JRC128515

2001-0370 (online),   

https://doi.org/10.1016/j.csbj.2022.03.024,    https://publications.jrc.ec.europa.eu/repository/handle/JRC128515,   

10.1016/j.csbj.2022.03.024 (online),