biostudies-literatureSerra AAcademy of FinlandEuropean UnionEuropean Union Horizon2031https://www.ebi.ac.uk/biostudies/studies/S-EPMC9228743biostudies-literatureUnknown12(12)The molecular effects of exposures to engineered nanomaterials (ENMs) are still largely unknown. In classical inhalation toxicology, cell composition of bronchoalveolar lavage (BAL) is a toxicity indicator at the lung tissue level that can aid in interpreting pulmonary histological changes. Toxicogenomic approaches help characterize the mechanism of action (MOA) of ENMs by investigating the differentially expressed genes (DEG). However, dissecting which molecular mechanisms and events are directly induced by the exposure is not straightforward. It is now generally accepted that direct effects follow a monotonic dose-dependent pattern. Here, we applied an integrated modeling approach to study the MOA of four ENMs by retrieving the DEGs that also show a dynamic dose-dependent profile (dddtMONanomaterials (Basel, Switzerland)Characterization of ENM Dynamic Dose-Dependent MOA in Lung with Respect to Immune Cells Infiltration.PMC9228743322761814426Saarimaki LAPoulsen SSVogel UHalappanavar SKinaret PASFortino VSerra AGreco DDel Giudice GfalseCharacterization of ENM Dynamic Dose-Dependent MOA in Lung with Respect to Immune Cells Infiltration.The molecular effects of exposures to engineered nanomaterials (ENMs) are still largely unknown. In classical inhalation toxicology, cell composition of bronchoalveolar lavage (BAL) is a toxicity indicator at the lung tissue level that can aid in interpreting pulmonary histological changes. Toxicogenomic approaches help characterize the mechanism of action (MOA) of ENMs by investigating the differentially expressed genes (DEG). However, dissecting which molecular mechanisms and events are directly induced by the exposure is not straightforward. It is now generally accepted that direct effects follow a monotonic dose-dependent pattern. Here, we applied an integrated modeling approach to study the MOA of four ENMs by retrieving the DEGs that also show a dynamic dose-dependent profile (dddtMO2022-01-01T00:00:00Z2022 Jun2026-05-09T03:18:24.356Z2024-10-15T06:01:35.582ZS-EPMC92287433574537010.3390/nano12122031