Communication Disruption in the Immune System

Опубликована: Янв. 1, 2025

Язык: Английский

Prediction of Respiratory Irritation and Respiratory Sensitization of Chemicals Using Structural Alerts and Machine Learning Modeling

Toxics, Год журнала: 2025, Номер 13(4), С. 243 - 243

Опубликована: Март 25, 2025

Inhalation of toxic substances and contaminants can have adverse effects on the respiratory tract, leading to a range health problems, such as irritation inflammation, allergic reaction asthma, lung damage, or even death. It is not possible experimentally evaluate toxicity for all thousands chemicals in use. Here, we generated structural alerts developed machine learning (ML) classification models predict sensitization hazards using experimental data from publicly available databases literature. We identified 13 irritants 18 sensitizers. also set each hazard different types molecular descriptors ML techniques. Five best performing were combined into consensus model irritation, four individual used develop sensitization. The prediction accuracy was 84% training 88% test set, 86% both sets. A combination screen occupational- military-relevant chemicals. Out 687 screened occupational chemicals, 62 compounds 121 sensitizers, while 47 predicted 36 sensitizers list 525

Язык: Английский

Limitations and Modifications of Skin Sensitization NAMs for Testing Inorganic Nanomaterials

Toxics, Год журнала: 2024, Номер 12(8), С. 616 - 616

Опубликована: Авг. 21, 2024

Since 2020, the REACh regulation requires toxicological data on nanoforms of materials, including assessment their skin-sensitizing properties. Small molecules’ skin sensitization potential can be assessed by new approach methodologies (NAMs) addressing three key events (KE: protein interaction, activation dendritic cells, and keratinocytes) combined in a defined (DA) described OECD guideline 497. In present study, applicability NAMs (DPRA, LuSens, h-CLAT) to nine materials (eight inorganic nanomaterials (NM) consisting CeO2, BaSO4, TiO2 or SiO2, quartz) was evaluated. The were technically applicable NM using specific sample preparation (NANOGENOTOX dispersion protocol) method modifications reduce interaction with photometric flowcytometric read-outs. results assays according No. 497; two identified as sensitizers. However, from animal studies (for ZnO, also human data) indicate no potential. remaining seven test substances “inconclusive” because all outside domain DPRA, achievable concentrations not sufficiently high current guidelines NAMs. use these for (inorganic) relevance general are challenged ways: (i) need modification insoluble, matter; (ii) lack adequate concentration metrics top NM; (iii) may cause same molecular cellular small organic molecules do; fact, T-cell-mediated hypersensitivity most relevant reaction immune system NM. We conclude that adopted currently good fit testing

Язык: Английский