Table 2.

Hepatotoxicity of EGCG based on animal models.

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 γH2AX 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 γH2AX 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 γH2AX were increased.
	1500		Single dose	ALT was increased by 108-fold. Mouse survival was reduced by 85%. EGCG-2′-cysteine and EGCG-2″-cysteine were detected in the urine.
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′-cysteinyl and EGCG-2″-cysteinyl) were detected in the urine.	[74]
Female Swiss-Webster mice	50	i.p.	7 d	67% of mice died. Plasma ALT activity was elevated. Severe hepatic necrosis occurred.	[75]