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

ABSTRACT:

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 calcula

SUBMITTER: de Avila RI 

PROVIDER: S-EPMC11885506 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature