Cinnamyl acetate

Cinnamyl acetate, used in fragrances and as flavor ingredient, has been discussed by several institutions. In 1965, the compound was designated as generally recognized as safe as a flavor ingredient by the Flavor and Extract Manufacturers Association (FEMA). The association determined the average maximum use levels in several products that were considered to be safe: The European Parliament registered cinnamyl acetate as both a flavoring substance and a cosmetic compound in 1996. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) described in 2000 that “the substance does not present a safety concern at current levels of intake when used as a flavouring agent”. Cinnamyl acetate is also permitted by the U.S. Food & Drug administration for use as flavoring agent in food if the minimum quantity needed for its effect is used. == Production and intake ==

Estimates of the average annual production and daily intake of cinnamyl acetate as flavoring agent are reported by the WHO. According to this report, the annual volume of production in Europe is 1498 kg, and in the USA 2255 kg. The daily intake per person in Europe is estimated to be 210 μg, and in the USA 300 μg. Per kg body weight the daily intake is estimated for Europeans to be 4 μg/kg and for Americans to be 5 μg/kg. == Synthesis ==

Since cinnamyl acetate is naturally occurring in plants, it can be extracted and purified to obtain the compound. However, this has a low yield and therefore the production costs are high. The use of chemical methods can offer more efficient strategies to produce cinnamyl acetate. :: Since acetaldehyde has an unfavorable deactivating effect on the lipase used in the synthesis, ethyl acetate can be used as reactant instead of vinyl acetate. In this transesterification reaction cinnamyl alcohol 1 reacts with ethyl acetate to form cinnamyl acetate 2 and ethanol. This synthesis requires the lipase Novozym 435, and is performed in a solvent-free system. The reaction is as follows: :: Besides these three examples, there are many more ways to synthesize cinnamyl acetate. The addition reaction of dinitrogen trioxide to cinnamyl acetate produces an intermediate in the synthesis of chloramphenicol. == Metabolism ==

Cinnamyl acetate belongs to the group of cinnamyl derivatives. In general, these cinnamyl derivatives are absorbed from the gut very quickly, after which they are metabolized and excreted as polar metabolites in the urine or feces within 24 hours. Within the cinnamyl derivatives, cinnamyl acetate belongs to the group of cinnamyl esters. After absorption from the gut, this group of compounds is first hydrolyzed to cinnamyl alcohol by carboxylesterases. Carboxylesterases are a group of enzymes. The most important enzymes within this group are the A-esterases. These are present in most body tissues, but they are prevalent in the hepatocytes. Subsequently, the cinnamyl alcohol is oxidized which leads to the formation of cinnamaldehyde. This reaction is catalyzed by human NAD+-dependent alcohol dehydrogenase. Now, there are two routes for the further biotransformation of cinnamaldehyde. The minor route of biotransformation is the S-glutathionylation. The major route, however, is the conversion of cinnamaldehyde into cinnamic acid by the enzyme aldehyde dehydrogenase. Next, the cinnamic acid is transformed into cinnamoyl CoA which is again converted to either cinnamoylglycine by N-acyl transferase or to benzoyl CoA through β-oxidation, the latter being the major route. Intermediate metabolites in the β-oxidation pathway can be converted to 3-hydroxy-3-phenylpropionic acid and acetophenone, which can be excreted via the urine. However, the conversions of these intermediate metabolites are minor routes. Finally, the benzoyl CoA is conjugated with glycine under formation of hippuric acid or it is hydrolyzed generating free benzoic acid. This can be excreted via the urine directly or after glucuronidation. Hippuric acid, which is the major metabolite, is also excreted via the urine. :: == Toxicity ==

Since cinnamyl acetate is used as both a fragrance material and a food flavoring ingredient, dermal and oral exposure are considered to be the major routes of absorption. The dermal systematic exposure of cinnamyl acetate via cosmetic products is estimated to be 0.0115 mg/kg body weight/day. Furthermore, studies on the dermal toxicity were performed. Experiments on rabbits resulted in an LD50 of more than 5.0 g/kg, but no clinical effects were observed. Moreover, the level of skin irritation in swines was tested via a 48-h patch test. In this study, 0.05 g of cinnamyl acetate was applied and no irritation was observed. Another two experiments examined the skin irritation caused by 0.1 mL cinnamyl acetate on guinea pigs and rabbits via a direct application on the skin (open application). Mild to moderate irritation was observed in these experiments. == Effects on animals ==

Cinnamyl acetate is found in the leaf oils of the Cinnamomum osmophloeum tree, which grows in central and northern Taiwan. It is found that these oils have antibacterial, antimildew, antitermite, antimite, antifungal and anti-inflammatory activities. Furthermore, the oils show mosquito larvicidal activity against Aedes aegypti and Aedes albopictus larvae. However, cinnamyl acetate serves only a minor role in these activities. Moreover, cinnamyl acetate has a repellent effect on the mosquito Anopheles gambiae, and is therefore useful to protect against these insects. == References ==