Green tea extract-induced lethal toxicity in fasted but not in nonfasted dogs

Int J Toxicol. 2011 Feb;30(1):19-20. doi: 10.1177/1091581810387445. Epub 2010 Nov 22.


Recent chronic toxicity studies performed on green tea extracts in fasted dogs have revealed some unique dose-limiting lethal liver, gastrointestinal, and renal toxicities. Key findings included necrosis of hepatic cells, gastrointestinal epithelia and renal tubules, atrophy of reproductive organs, atrophy and necrosis of hematopoietic tissues, and associated hematological changes. The polyphenol cachetins (a mixture of primarily epigallocatechin gallate [≥55%]; plus up to 10% each of epigallocatechin, epicatechin, and epigallocatechin gallate) appeared to be the causative agents for the observed toxicities because they are the active ingredients of green tea extract studied. Conduct of the study in nonfasted dogs under the same testing conditions and dose levels showed unremarkable results. Assuming both studies were valid, at the identified no observed adverse effect levels (NOAEL) of each study, systemic exposures (based on area under the curve [AUC]) were actually lower in fasted than nonfasted dogs, suggesting that fasting may have rendered the target organ systems potentially more vulnerable to the effects of green tea extract. The toxicity mechanisms that produced lethality are not known, but the results are scientifically intriguing. Because tea drinking has become more popular in the United States and abroad, the mode of action and site of action of green tea extract-induced lethal toxicities during fasting and the role of other phytochemical components of Folia Camellia sinensis (including nonpolyphenol fractions, which are often consumed when whole-leaf products are presented) warrant further investigation.

MeSH terms

  • Animals
  • Antioxidants / pharmacokinetics
  • Antioxidants / toxicity*
  • Area Under Curve
  • Camellia sinensis / chemistry*
  • Catechin / pharmacokinetics
  • Catechin / toxicity*
  • Dogs
  • Dose-Response Relationship, Drug
  • Enterocytes / drug effects
  • Enterocytes / pathology
  • Female
  • Food Deprivation*
  • Hepatocytes / drug effects
  • Hepatocytes / pathology
  • Kidney Tubules / drug effects
  • Kidney Tubules / pathology
  • Longevity / drug effects
  • Male
  • Necrosis / chemically induced
  • No-Observed-Adverse-Effect Level
  • Plant Extracts / pharmacokinetics
  • Plant Extracts / toxicity


  • Antioxidants
  • Plant Extracts
  • Catechin