Metabolite Platform Biofluid log2ALT Hepatic necrosis All Doses animals HDALL All Dosesanimals HDALL Arginine LC-MS/MS Blood -0.50 -0.66 -0.41 -0.47 2-Oxoarginine LC_POS Urine -0.58 -0.59 -0.60 -0.54 Decenedioic acid LC_NEG Urine 0.64 0.62 0.59 0.51 Taurodeoxycholic acid LC_NEG Blood 0.30 0.64 0.27 0.60 Sulfolithcholylglycine LC_NEG Blood 0.65 0.72 0.54 0.57 Sebacic acid LC_NEG Urine 0.75 0.77 0.74 0.70 Azelaic acid LC_POS Blood 0.52 0.81 0.22 0.42 Undecanedioic acid LC_POS Blood 0.59 0.83 0.32 0.47 Taurocholic acid LC-MS/MS Blood 0.73 0.86 0.27 0.60 α-Ketoglutarate GC-MS Blood 0.88 0.96 0.70 0.72 log2ALT Clinic Blood 1 1 0.72 0.73

Table 3: Metabolites with strong Pearson’s correlations to log2ALT and hepatic necrosis scores. Pearson’s rank correlations were based on the correlations between metabolites and log2ALT and hepatic necrosis scores at all dose levels (control, LD, HD) and metabolites at high dose (HD) from all time points to discover good injury biomarkers.