Coumarin is a
chemical compound (specifically, a
benzopyrone) found in many
plants, notably in high concentration in the
tonka bean (
Dipteryx odorata), vanilla grass (
Anthoxanthum odoratum),
woodruff (
Galium odoratum),
mullein (
Verbascum spp.), and
sweet grass (
Hierochloe odorata). It has a sweet scent, readily recognised as the scent of newly-mown
hay, and has been used in perfumes since 1882. It has clinical medical value as the precursor for several
anticoagulants, notably
warfarin, and is used as a
gain medium in some
dye lasers.
The name comes from a French word,
coumarou, for the
tonka bean.
Synthesis
The
biosynthesis of coumarin in plants is via
hydroxylation,
glycolysis and
cyclization of
cinnamic acid. Coumarin can be prepared in a laboratory in a
Perkin reaction between
salicylaldehyde and
acetic anhydride.
The
Pechmann condensation provides another synthesis of coumarin and its derivatives.
Biological function
Coumarin has appetite-suppressing properties, suggesting its widespread occurrence in plants, especially grasses, is because of its effect of reducing the impact of grazing animals.
Derivatives
Some naturally occurring coumarin derivatives include
umbelliferone (7-hydroxycoumarin), aesculetin (6,7-dihydroxycoumarin),
herniarin (7-methoxycoumarin),
psoralen and
imperatorin. Coumarin and its derivatives are all considered
phenylpropanoids.
Medical use
Coumarin has been used in the treatment of
lymphedema.
Toxicity and use in foods, beverages, tobacco, and cosmetics
Coumarin is moderately toxic to the liver and kidneys, with an
LD50 of 275 mg/kg—low compared to related compounds. Although only somewhat dangerous to humans, coumarin is a potent
rodenticide: rats and other rodents largely metabolize it to 3,4-coumarin epoxide, a toxic compound that can cause
internal hemorrhage and death. Humans largely metabolize it to 7-hydroxycoumarin, a compound of lower toxicity. The German Federal Institute for Risk Assessment has established a
tolerable daily intake of 0.1 mg coumarin per kg body weight, but also advises that, [if] this level is exceeded for a short time only, there
is no threat to health.
For example, a person weighing 135 lbs or about 61 kg would have a TDI of approximately 6.1 mg of coumarin.
European health agencies have warned against consuming high amounts of
cassia bark, one of the four species of
cinnamon, because of its coumarin content.
According to the German Federal Institute for Risk Assessment, 1 kg of (
cassia)
cinnamon powder contains approximately 2100 to 4400 mg of coumarin.
Powdered Cassia Cinnamon weighs 0.56 g/cc; therefore, 1 kg of Cassia Cinnamon powder is equal to 362.29 teaspoons (1000 g divided by 0.56 g/cc multiplied by 0.20288 tsp/cc). This means 1 teaspoon of cinnamon powder contains 5.8 to 12.1 mg of coumarin, which may be above the Tolerable Daily Intake for smaller individuals.
However, it is important to note that the German Federal Institute for Risk Assessment only cautions against high daily intakes of foods containing coumarin.
Chamomile, a common herbal tea, also contains coumarin.
Coumarin is often found in
tobacco products and artificial
vanilla substitutes, despite having been banned as a food additive in numerous countries since the mid-20th century. Coumarin was banned as a food additive in the United States in 1978.
OSHA considers this compound to be only a lung-specific carcinogen, and "not classifiable as to its carcinogenicity to humans". Coumarin was banned as an adulterant in cigarettes by tobacco companies in 1997, but due to the lack of reporting requirements to the US
Department of Health and Human Services it was still being used as a flavoring additive in pipe tobacco. Coumarin is currently listed by the United States
Food and Drug Administration (FDA) among "Substances Generally Prohibited From Direct Addition or Use as Human Food", according to 21
CFR 189.130, but some natural additives containing coumarin (such as
Sweet Woodruff) are allowed "in alcoholic beverages only" (21
CFR 172.510). In Europe, such beverages are very popular, for example
Maiwein (white wine with woodruff) and
Żubrówka (vodka flavoured with bison grass).
Coumarin should be avoided by people with perfume allergy.
Flexitral (
Chantilly, Virginia) has developed an allergen replacement product called Coumane (
™), GRAS.
Related compounds and derivatives
Compounds derived from coumarin are also called "coumarins". Compounds within this coumarin family include:
Several of the above compounds are used as
anticoagulant drugs and/or as
rodenticides.
Use As a Pesticide and Antidote
Coumarins are potent
rodenticides because they block the synthesis of Vitamin K, especially in
rodents, giving it strong
anticoagulatory and
rodenticidal properties. Death occurs after a period of between several days to two weeks, usually from internal hemorrhaging.
Vitamin K is a true
antidote for poisoning by coumarins such as
bromadiolone. Treatment usually comprises a large dose of Vitamin K given intravenously immediately, followed by doses in pill form for a period of at least two weeks, though usually three to four, afterwards. If caught early, prognosis is good, even when large amounts are ingested.
