Animal type EGCG dosage (mg/kg/d) Route of administration Duration Results Reference Female Swiss albino mice 108, 67.8, 21.1, and 6.6 i.p. and p.o. 14 d i.p. treatment increased serum bilirubin markers; p.o. treatment did not show any dose-dependent changes except ALT marker. 14 d tolerable dose of EGCG was 21.1 mg/kg for i.p. and 67.8 mg/kg for p.o. [67 ] Male Kunming mice 55 i.p. 5 d Serum ALT, AST, 4-HNE, IL-2, IL-6, and IL-10 and hepatic γ H2AX were raised. Hepatic Nrf2-target gene expression was increased. [70 ] 70 2 d The fatality rate was 100%. 125 Single dose Serum ALT, AST, 4-HNE, IL-6, and IL-10 and hepatic γ H2AX were raised. Hepatic nuclear and cytosolic Nrf2 proteins were suppressed. Male Kunming mice 45 i.p. 7 d Mouse growth was not affected. The dosage was considered as maximum tolerable dose. [71 ] 55 and 75 5 d Hepatotoxicity occurred. Major hepatic antioxidant enzymes were suppressed. Nrf2-mediated rescue response was induced. 75, 100, 200, and 400 Single dose Mice died in a dose-dependent manner. 200 4, 12, and 24 h The Nrf2 pathway was not activated; Nrf2 and its target genes were suppressed. Male ND-4 mice 750 i.g. 5 d ALT was slightly increased. Histopathology of the liver showed congestion of sinusoids and central and portal veins. [72 ] 1500 Single dose ALT was markedly increased. Histopathology of the liver showed degenerative hepatocytes and a small number of vacuoles. Male CF-1 mice 500 i.g. 7 d Mouse survival was reduced by 30%. [65 ] 750 7 d Mouse survival was reduced by 75%. Hepatic MDA, MT, and γ H2AX were increased. 1500 Single dose ALT was increased by 108-fold. Mouse survival was reduced by 85%. EGCG-2 Wistar rats of both sexes 1868 p.o. Single dose Mice were lethargic and their respiration was labored. [73 ] Male CD-1 mice 100, 150, and 300 i.p. Single dose Plasma ALT was increased. Mice died within 24 h. [68 ] Mice 50, 200, and 400 i.p. 24 h EGCG thiol conjugates (EGCG-2 [74 ] Female Swiss-Webster mice 50 i.p. 7 d 67% of mice died. Plasma ALT activity was elevated. Severe hepatic necrosis occurred. [75 ]
