Toxicology and risk assessment of coumarin: focus on human data.
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.
Abraham
Klaus
K
Federal Institute for Risk Assessment (BfR), 14195 Berlin, Germany. klaus.abraham@bfr.bund.de
Wöhrlin
Friederike
F
Lindtner
Oliver
O
Heinemeyer
Gerhard
G
Lampen
Alfonso
A
D000818:Animals; D001711:Biotransformation / Q000235:genetics; D056486:Chemical and Drug Induced Liver Injury; D003374:Coumarins / Q000592:standards / Q000627:therapeutic use / Q000633:toxicity*; D004487:Edema / Q000188:drug therapy; D005421:Flavoring Agents / Q000008:administration & dosage / Q000592:standards / Q000633:toxicity*; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced; D008209:Lymphedema / Q000188:drug therapy; D010946:Plants, Medicinal / Q000737:chemistry; D018570:Risk Assessment; D013045:Species Specificity; D018675:Toxicity Tests; D014689:Venous Insufficiency / Q000503:physiopathology
D003374:Coumarins; D005421:Flavoring Agents; C030123:coumarin