Coumarin in flavourings and other food ingredients with flavouring properties ‐ Scientific Opinion of the Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (AFC)

The metabolism, toxicity and results of tests for carcinogenicity have been reviewed with respect to the safety for humans of coumarin present in foodstuffs and from fragrance use in cosmetic products. Coumarin is a natural product which exhibits marked species differences in both metabolism and toxicity. The majority of tests for mutagenic and genotoxic potential suggest that coumarin is not a genotoxic agent. The target organs for toxicity and carcinogenicity in the rat and mouse are primarily the liver and lung. Moreover, the dose-response relationships for coumarin-induced toxicity and carcinogenicity are non-linear, with tumour formation only being observed at high doses which are associated with hepatic and pulmonary toxicity. Other species, including the Syrian hamster, are seemingly resistant to coumarin-induced toxicity. There are marked differences in coumarin metabolism between susceptible rodent species and other species including humans. It appears that the 7-hydroxylation pathway of coumarin metabolism, the major pathway in most human subjects but only a minor pathway in the rat and mouse, is a detoxification pathway. In contrast, the major route of coumarin metabolism in the rat and mouse is by a 3,4-epoxidation pathway resulting in the formation of toxic metabolites. The maximum daily human exposure to coumarin from dietary sources for a 60-kg consumer has been estimated to be 0.02 mg/kg/day. From fragrance use in cosmetic products, coumarin exposure has been estimated to be 0.04 mg/kg/day. The total daily human exposure from dietary sources together with fragrance use in cosmetic products is thus 0.06 mg/kg/day. No adverse effects of coumarin have been reported in susceptible species in response to doses which are more than 100 times the maximum human daily intake. The mechanism of coumarin-induced tumour formation in rodents is associated with metabolism-mediated, toxicity and it is concluded that exposure to coumarin from food and/or cosmetic products poses no health risk to humans.

Coumarin is a component of natural flavourings including cassia, which is widely used in foods and pastries. The toxicity of coumarin has raised some concerns and food safety authorities have set a maximum limit of 2mg/kg for foods and beverages in general, and a maximum level of 10mg/l for alcoholic beverages. An efficient method for routine analysis of coumarin is liquid chromatography with diode array detection. The optimal sample preparation for foods containing cinnamon was investigated and found to be cold extraction of 15g sample with 50mL of methanol (80%, v/v) for 30min using magnetic stirring. In the foods under investigation, appreciable amounts of coumarin were found in bakery products and breakfast cereals (mean 9mg/kg) with the highest concentrations up to 88mg/kg in certain cookies flavoured with cinnamon. Other foods such as liqueurs, vodka, mulled wine, and milk products did not have coumarin concentrations above the maximum level. The safety assessment of coumarin containing foods, in the context of governmental food controls, is complicated as a toxicological basis for the maximum limits appears to be missing. The limits were derived at a time when a genotoxic mechanism was assumed. However, this has since been disproven in more recent studies. Our exposure data on coumarin in bakery products show that there is still a need for a continued regulation of coumarin in foods. A toxicological re-evaluation of coumarin with the aim to derive scientifically founded maximum limits should be conducted with priority.

Lymphedema of the arms can be a serious consequence of local and regional therapy in women with breast cancer. Coumarin has been reported to be effective for the treatment of women with lymphedema; we undertook a study in which we attempted to replicate those findings.