Benchmark Dose Estimation from Transcriptomics Data for Methylimidazolium Ionic Liquid Hepatotoxicity: Implications for Health Risk Assessment of Green Solvents DOI Creative Commons

Qing Yang,

Xiaole Zhao,

Kejia Wu

et al.

Environment & Health, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 12, 2024

Ionic liquids (ILs), traditionally considered environmentally benign solvents, have shown potential toxicity to organisms, raising concerns about their safety. Among them, 1-octyl-3-methylimidazolium (M8OI) has been detected at high concentrations in soils and exhibits hepatotoxic properties. To uncover the molecular mechanisms underlying this toxicity, whole-transcriptome sequencing was performed, coupled with benchmark dose (BMD) modeling, derive transcriptomic points-of-departure (tPOD) through dose–response analysis. The analysis identified 425, 667, 567 differentially expressed genes (DEGs) following low (10 μmol/L), medium (50 (200 μmol/L) doses of M8OI exposure, respectively. Enrichment revealed significant perturbations pathways related cytokine–cytokine receptor interaction IL-17 signaling. BMD modeling yielded tPOD values 1.51 μmol/L (median 20 most sensitive genes, omicBMD20), 2.98 (tenth percentile all omicBMD10th), 6.83 (mode first peak gene BMDs, omicBMDmode), 5.9 for pathway-level These transcriptomics-derived tPODs were least 105-fold lower than M8OI's concentration, as indicated by its EC50 723.6 HepG2 cells. Functional data legionellosis, rheumatoid arthritis, transcriptional misregulation cancer affected M8OI. findings highlight driving M8OI-induced hepatotoxicity underscore utility transcriptomics deriving quantitative thresholds. results provide critical insights guideline-driven toxicological evaluations regulatory decision-making, supporting a more comprehensive assessment IL

Language: Английский

Benchmark Dose Estimation from Transcriptomics Data for Methylimidazolium Ionic Liquid Hepatotoxicity: Implications for Health Risk Assessment of Green Solvents DOI Creative Commons

Qing Yang,

Xiaole Zhao,

Kejia Wu

et al.

Environment & Health, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 12, 2024

Ionic liquids (ILs), traditionally considered environmentally benign solvents, have shown potential toxicity to organisms, raising concerns about their safety. Among them, 1-octyl-3-methylimidazolium (M8OI) has been detected at high concentrations in soils and exhibits hepatotoxic properties. To uncover the molecular mechanisms underlying this toxicity, whole-transcriptome sequencing was performed, coupled with benchmark dose (BMD) modeling, derive transcriptomic points-of-departure (tPOD) through dose–response analysis. The analysis identified 425, 667, 567 differentially expressed genes (DEGs) following low (10 μmol/L), medium (50 (200 μmol/L) doses of M8OI exposure, respectively. Enrichment revealed significant perturbations pathways related cytokine–cytokine receptor interaction IL-17 signaling. BMD modeling yielded tPOD values 1.51 μmol/L (median 20 most sensitive genes, omicBMD20), 2.98 (tenth percentile all omicBMD10th), 6.83 (mode first peak gene BMDs, omicBMDmode), 5.9 for pathway-level These transcriptomics-derived tPODs were least 105-fold lower than M8OI's concentration, as indicated by its EC50 723.6 HepG2 cells. Functional data legionellosis, rheumatoid arthritis, transcriptional misregulation cancer affected M8OI. findings highlight driving M8OI-induced hepatotoxicity underscore utility transcriptomics deriving quantitative thresholds. results provide critical insights guideline-driven toxicological evaluations regulatory decision-making, supporting a more comprehensive assessment IL

Language: Английский

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