Inhal Toxicol. 2026 Mar 23:1-14. doi: 10.1080/08958378.2026.2644247. Online ahead of print.
ABSTRACT
BACKGROUND: Six years since the revised Test Guidelines 412 and 413 (TG412 and TG413) were issued, there are sufficient data to evaluate the relationship between bronchoalveolar lavage (BAL) cytology and biomarkers with histopathology.
OBJECTIVE: This retrospective study evaluates the correlation between mandatory endpoints in the BAL fluid (LDH activity, concentration of total protein, inflammatory cell counts) and histopathological changes in the lungs following sub-chronic inhalation exposure in rats.
MATERIALS AND METHODS: Twenty-eight studies conducted across two Test Facilities from 2018 to 2023 were reviewed to identify trends.
RESULTS: At baseline, there were no strain differences in BAL fluid total protein, but LDH activity was statistically different between sexes and ages. LDH activity and total protein in BALF at the lowest observed adverse effect concentration showed no pathological pattern following inhalation exposure to the tested chemicals, while immune cell counts shifted in Wistar Han rats. Specifically in studies with adverse lung histopathology, total protein and LDH activity were generally elevated, along with a shift in immune cells toward neutrophils and eosinophils, without correlation to the severity score of adverse microscopic findings.
CONCLUSION: These results suggest that BALF parameters are insufficient to independently characterize adversity but may be used in other ways to progress new approach methods.
PMID:41870483 | DOI:10.1080/08958378.2026.2644247
