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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
- Benchmark doses for significantly enriched pathways were lowest at 13
- 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
- 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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