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EC number: 200-001-8 | CAS number: 50-00-0
- Patterns of gene expression varied with concentration and duration.
- At 2 ppm, sensitive response genes (SRGs)—associated with cellular stress, thiol transport/reduction, inflammation, and cell proliferation—were upregulated at all exposure durations.
- At 6 ppm and greater, gene expression changes showed enrichment of pathways involved in cell cycle, DNA repair, and apoptosis.
- ERBB, EGFR, WNT, TGF-b, Hedgehog, and Notch signaling were also enriched.
- Benchmark doses for significantly enriched pathways were lowest at 13 weeks.
- Transcriptional and histological changes at 6 ppm and greater corresponded to dose ranges in which the PK model predicted significant reductions in free GSH and increases in FAcetal.
- Genomic changes at 0.7–2 ppm likely represent changes in extracellular FAcetal and GSH.
- DNA replication stress, enhanced proliferation, squamous metaplasia, and stem cell niche activation appear to be associated with FA carcinogenesis.
- Dose dependencies in MOA, high background FAcetal, and nonlinear FAcetal/GSH tissue kinetics indicate that FA concentrations below 1 or 2 ppm would not increase risk of cancer in the nose or any other tissue or affect FA homeostasis within epithelial cells.
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