Coumarin is a naturally occurring product derived from the Tonka bean and has been employed for over 100 years. It is used in consumer products and as a therapeutic agent, for instance in the treatment of cancer and infectious disease. During the 1950s, doubt was cast on coumarin's safety when experiments produced liver damage in laboratory rats. As a result, coumarin was banned as a food flavouring agent.(1)
Subsequent research, however, showed wide species variation in response to coumarin. While dogs also suffer liver toxicity, there are only minimal effects in baboons.(2) And doses which damage the rat's liver are harmless to gerbils.1 Even different strains of the same species react differently and coumarin is less harmful to the DBA/2J strain of laboratory mouse than the CH3/HeJ strain.(3)
Among patients receiving relatively high doses of coumarin for therapeutic purposes, liver toxicity is said to be "very rare", (1) and rats and dogs are now considered poor "models" for assessing the drug because they metabolise coumarin in a completely different way. (1,2,3)
1) J.H.Fentem et al, Toxicology, 1992, vol.71, 129-136.
2) J.G.Evans et al, Food & Cosmetic Toxicology, 1979, vol. 17, 187-193.
3) W.Endell & G.Seidel, Agents & Actions, 1978, vol.8, 299-302.
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