Toxicology and risk assessment of coumarin: focus on human data

Mol Nutr Food Res. 2010 Feb;54(2):228-39. doi: 10.1002/mnfr.200900281.


Coumarin is a secondary phytochemical with hepatotoxic and carcinogenic properties. For the carcinogenic effect, a genotoxic mechanism was considered possible, but was discounted by the European Food Safety Authority in 2004 based on new evidence. This allowed the derivation of a tolerable daily intake (TDI) for the first time, and a value of 0.1 mg/kg body weight was arrived at based on animal hepatotoxicity data. However, clinical data on hepatotoxicity from patients treated with coumarin as medicinal drug is also available. This data revealed a subgroup of the human population being more susceptible for the hepatotoxic effect than the animal species investigated. The cause of the high susceptibility is currently unknown; possible mechanisms are discussed. Using the human data, a TDI of 0.1 mg/kg body weight was derived, confirming that of the European Food Safety Authority. Nutritional exposure may be considerably, and is mainly due to use of cassia cinnamon, which is a popular spice especially, used for cookies and sweet dishes. To estimate exposure to coumarin during the Christmas season in Germany, a telephone survey was performed with more than 1000 randomly selected persons. Heavy consumers of cassia cinnamon may reach a daily coumarin intake corresponding to the TDI.

Publication types

  • Review

MeSH terms

  • Animals
  • Biotransformation / genetics
  • Chemical and Drug Induced Liver Injury
  • Coumarins / standards
  • Coumarins / therapeutic use
  • Coumarins / toxicity*
  • Edema / drug therapy
  • Flavoring Agents / administration & dosage
  • Flavoring Agents / standards
  • Flavoring Agents / toxicity*
  • Humans
  • Liver Neoplasms / chemically induced
  • Lymphedema / drug therapy
  • Plants, Medicinal / chemistry
  • Risk Assessment
  • Species Specificity
  • Toxicity Tests
  • Venous Insufficiency / physiopathology


  • Coumarins
  • Flavoring Agents
  • coumarin