Evaluation of a non-animal toolbox informed by adverse outcome pathways for human inhalation safety.

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Tác giả: Maria Teresa Baltazar, Hugh Barlow, Danilo Basili, Holger Peter Behrsing, Bernadett Boda, Anthony M Bowden, Samuel Constant, Renato Ivan de Ávila, Patrik Engi, Alistair Mark Middleton, Iris Müller, Vivek Patel, Tymoteusz Pietrenko, Ouarda Saib, Mathura Theiventhran, Joanne Wallace

Ngôn ngữ: eng

Ký hiệu phân loại: 531.3 Solid dynamics

Thông tin xuất bản: Switzerland : Frontiers in toxicology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 683083

INTRODUCTION: This work evaluated a non-animal toolbox to be used within a next-generation risk assessment (NGRA) framework to assess chemical-induced lung effects using human upper and lower respiratory tract models, namely MucilAir™-HF and EpiAlveolar™ systems, respectively. METHODS: A 12-day substance repeated exposure scheme was established to explore potential lung effects through analysis of bioactivity readouts from the tissue integrity and functionality, cytokine/chemokine secretion, and transcriptomics. RESULTS: Eleven benchmark chemicals were tested, including inhaled materials and drugs that may cause lung toxicity following systemic exposure, covering 14 human exposure scenarios classified as low- or high-risk based on historical safety decisions. For calculation of bioactivity exposure ratios (BERs), obtained chemical-induced bioactivity data were used to derive DISCUSSION: In general, PoDs occurred at higher concentrations than the corresponding human exposure values for the majority of the low-risk chemical-exposure scenarios. For all the high-risk chemical-exposure scenarios, there was a clear overlap between the PoDs and lung deposited mass and C
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