Cinnamaldehyde was reviewed at the eleventh meeting of the Joint
    FAO/WHO Expert Committee on Food Additives, specifications were
    prepared, and a conditional acceptable daily intake for man (ADI) of
    0-1.25 mg/kg bw was established (FAO/WHO, 1967; FAO/WHO, 1968).

         Since this previous review, new data on cinnamaldehyde and
    closely related compounds have become available and are included in
    this monograph.



         Cinnamaldehyde administered intraperitoneally to a rabbit was
    excreted in the urine as cinnamic acid, cinnamoylglycine, benzoic acid
    and hippuric acid (Friedman & Mai, 1931).

         Since cinnamaldehyde is oxidized in vivo to cinnamic acid
    (Friedman & Mai, 1931; F.E.M.A., 1978), a consideration of the data on
    the toxicity and metabolism of cinnamic acid is pertinent to the
    evaluation of cinnamaldehyde. In this regard, considerable information
    is available on cinnamic acid (Opdyke, 1978; F.E.M.A., 1978).

         The oral LD50 for rats varies from 2.5 g/kg to greater than
    5.0 g/kg. Values greater than 5.0 g/kg have been reported for mice and
    guinea-pigs. The dermal LD50 for rabbits is greater than 5.0 g/kg
    (Opdyke, 1978; F.E.M.A., 1978).

         Cinnamic acid was administered orally in repeated daily doses of
    5 or 50 mg/kg to pregnant rats for the entire course of pregnancy.
    Sacrifice and examination of a half of the animals on day 20 of
    gestation revealed no embryotoxic effects as judged by body weight,
    rate of survival, bone development, and determination of hepatic
    nucleic acids. Offspring produced from the other half of the animals
    were normal with respect to body weight, size, survival, and general
    development at birth and one month later (Zaitsev & Maganov, 1975).

         When (3-14C) cinnamic acid was injected into female rats, 48% of
    the label was excreted in the urine and 25% in the faeces; there was
    negligible incorporation in tissues and respiratory CO2; no urinary
    phenolic metabolites were detected. Identifiable metabolites included
    hippuric and benzoic acids, together with unchanged cinnamic acid
    (Teuchy & Van Sumere, 1971).

         In the rabbit cinnamic acid is excreted almost entirely as
    hippuric acid, there being no formation of cinnamoylglycine (Williams,

         In the dog, considerable excretion of glucuronide, probably of
    benzoyl glucuronide, has been observed and beta-phenyl-beta-
    oxopropionic acid, cinnamoylglycine and acetophenone were found as
    minor metabolites (Williams, 1959).

         Following the administration of single oral doses (6-6.7 g) of
    cinnamic acid or sodium cinnamate to humans, 60-90% was excreted in
    the urine as hippuric acid; a minor amount was accounted for as
    cinnamoyl glucuronide (Snapper et al., 1940; Snapper & Saltzman,


    Special studies on carcinogenicity

         In a 24-week screening test, groups of 15 male and 15 female A/He
    mice received in the first eight weeks of the test period, a total
    dose of 0.8 or 4.0 g/kg bw of cinnamaldehyde in 24 thrice-weekly i.p.
    injections. The higher dose had previously been calculated to be the
    maximum tolerated dose. There was no increase in the incidence of
    tumours of the lung, liver, kidney, spleen, thymus, intestine, or
    salivary or endocrine glands. Survival was reduced in high-dose males
    to 60% and in high-dose females to 75%, but survival in the low-dose
    groups was unaffected (Stoner et al., 1973).

    Special studies on pharmacological aspects

         Intraperitoneal injection of either a 250 or 500 mg/kg dose of
    cinnamaldehyde to mice resulted in ataxia, analgesia, hypothermia, a
    decrease in spontaneous motor activity, antagonism of methamphetamine-
    induced hyperactivity, and prolongation of sodium hexobarbital-induced
    anaesthesia. A 500 mg/kg dose was also observed to reduce development
    of a tonic convulsion in a nicotine-induced convulsion. Administration
    of a 125 mg/kg dose intraperitoneally produced hypothermia,
    antipyretcosis, and a prolongation of hexobarbital-induced anaesthesia
    (Harada & Osaki, 1972).

         Intraperitoneal injection of a single 250 mg/kg dose of
    cinnamaldehyde to mice produced an inhibition of intestinal propulsion
    while simultaneously protecting against the generation of stress-
    induced gastric erosion (Harada & Yano, 1975).


         Intravenous infusion of single 5-10 mg/kg doses of cinnamalde to
    anaesthetized dogs resulted in a 0-40% decrease in blood pressure for
    periods of one to seven minutes (Harada & Yano, 1975).

         Intravenous administration of 2.7-44.4 mg/kg cinnamaldehyde to
    dogs invoked, primarily, a depressor response exhibiting an initial
    significant sharp fall in blood pressure for a short period. This was
    followed by a slight rise in blood pressure over a longer period
    (Wingard et al., 1955).

    Acute toxicity


    Animal        Route    mg/kg bw    References

    Mouse         i.p.     610         Harada & Ozaki, 1972

    Mouse         oral     2 225       Harada & Ozaki, 1972

    Mouse         oral     3 400       Zaitsev & Rakhmanina, 1974

    Rat           oral     3 400       Zaitsev & Rakhmanina, 1974

    Rat           oral     2 220       Jenner et al., 1964

    Guinea-pig    oral     3 400       Zaitsev & Rakhmanina, 1974

    Guinea-pig    oral     1 160       Jenner et al., 1964

    Short-term studies


         A 12-week feeding study was carried out on groups of 12 male and
    12 female weanling rats using a blend of five related compounds
    (cinnamic aldehyde, methyl cinnamate, ethyl cinnamate, cinnamyl
    cinnamate, and alpha methyl cinnamic aldehyde), providing an estimated
    daily intake for cinnamaldehyde of 103.5 mg/kg bw (with a total daily
    intake for the blend of 115 mg/kg bw). No adverse effects were
    observed in rats of either sex as judged by appearance, behaviour,
    food intake, presence of sugar or albumin in the urine, blood
    haemoglobin, liver, kidney and brain weights, or gross pathology.
    However, the efficiency of food utilization was depressed in both
    sexes, and the growth of males (but not females) was moderately
    retarded (but not significantly as shown by statistical analysis)
    (Oser, 1967).

         In a second 12-week feeding study, groups of five male and five
    female weanling rats were maintained on diets containing only
    cinnamaldehyde at levels resulting in daily intakes of 58, 114 or
    227 mg/kg. No adverse effects were observed (at any of the dietary
    levels of cinnamaldehyde) on appearance, behaviour, growth, food
    consumption, efficiency of food utilization, presence of sugar or 
    albumin in the urine, blood haemoglobin, liver and kidney weights, or
    gross pathology (Oser, 1967).

         Since no adverse effects were observed in this experiment on
    cinnamaldehyde, alone, the authors concluded that the effects on
    growth (males) and on efficiency of food utilization (both sexes)
    observed in the earlier experiment, using a blend of five substances,
    must have been due to components of the blend other than
    cinnamaldehyde (Oser, 1967).

         Groups of 10 male and 10 female rats were maintained for 16 weeks
    on diets containing cinnamaldehyde at levels of 0, 1000, 2500 and
    10 000 ppm (approximately equivalent to 50, 125 and 500 mg/kg/day).
    Neither body weight gains, haematology, nor examination of the major
    organs revealed significant differences between the test and control
    animals at levels of either 1000 or 2500 ppm. None of the above
    parameters revealed adverse effects following a dietary intake of
    10 000 ppm for 16 weeks, with the exception of a "slight hepatic cell
    swelling" and a "slight hyperkeratosis of squamous portion" of the
    stomach, noted upon microscopic examination (Hagan et al., 1967).


         Cinnamaldehyde was reviewed at the eleventh JECFA and a
    conditional ADI of 0-1.25 mg/kg bw was established. There was further
    data available on two short-term feeding studies. However, as these
    did not include histopathology they could not be employed to set an
    ADI. The previous conditional ADI was converted to a temporary ADI.

         A monograph was prepared.


    Level causing no toxicological effect

    Rat: ppm in the diet equivalent to 125 mg/kg bw.

    Estimate of temporary acceptable daily intake for man

    0-0.7 mg/kg bw.


    Required by 1981.

    Two 90-day studies in rodent and non-rodent.


    Boyland, E. & Mawson, E. H. (1938) Experiments on the chemotherapy of
         cancer, Biochem. J., 32, 1982-1987

    FAO/WHO (1967) Toxicological evaluation of some flavouring substances
         and non-nutritive sweetening agents, FAO Nutrition Meetings
         Report Series No. 44a; WHO/Food Add./68.33

    FAO/WHO (1968) Specifications for the identity and purity of food
         additives and their toxicological evaluation: some flavouring
         substances and non-nutritive sweetening agents, Eleventh Report
         of the Joint FAO/WHO Expert Committee on Food Additives, FAO
         Nutrition Meetings Report Series No. 44; Wld Hlth Org. techn.
         Rep. Ser. No. 383

    F.E.M.A. (1978) Scientific literature review of cinnamyl alcohol and
         related substances on flavor usage. Published by the National
         Information Services under contract with the Food and Drug

    Friedman, E. & Mai, H. (1931) Behaviour of cinnamyl acetic acid and of
         cinnamaldehyde in the animal body, Biochem. Z., 242, 282-287
         (in German)

    Hagan, E. C. et al. (1967) Food flavourings and compounds of related
         structure. II. Subacute and chronic toxicity, Food Cosmet.
         Toxicol., 5, 141-157

    Harada, M. & Osaki, Y. (1972) Pharmacological studies on Chinese
         cinnamon. I. Central effects of cinnamaldehyde, Yakugaku
         Zasshi, 92 (2), 135-140 (in Japanese)

    Harada, M. & Yano, S. (1975) Pharmacological studies on Chinese
         cinnamon. II. Effects of cinnamaldehyde on the cardiovascular and
         digestive systems, Chem. Pharm. Bull., 23 (5), 941-947

    Jenner, P. M. et al. (1964) Food flavourings and compounds of related
         structure. I. Acute oral toxicity, Food Cosmet. Toxicol., 2,

    Opdyke, D. L. J. (1978) Fragrance raw materials monographs, Food
         Cosmet. Toxicol., 16, Suppl. 1, 687-689

    Oser, B. L. (1967) Unpublished report

    Snapper, I., Yu, T. F. & Chiang, Y. T. (1940) Cinnamic acid metabolism
         in man, Proc. Soc. Exp. Biol. Med., 44, 30-34

    Snapper, I. & Saltzman, A. (1948) Excretion of glucuronates after
         ingestion of benzoic acid or cinnamic acid as a test of liver
         function, Conf. on Liver Injury, Trans. 7th Conf., pp. 77-85
         (discussion, pp. 85-86) (cited by F.E.M.A., 1978)

    Teuchy, H. & Van Sumere, C. F. (1971) The metabolism of (1-14C)
         phenylalanine, (3-14C) cinnamic acid, and (2-14C) ferulic acid
         in the rat, Arch. Int. Physiol. Biochem., 79 (3), 589-618

    Williams, R. T. (1959) Detoxication mechanisms, The metabolism and
         detoxication of drugs, toxic substances and other compounds,
         London, Chapman & Hall Ltd, 2nd ed.

    Wingard, C., Hitchcock, P. & Teague, R. S. (1955) A survey of the
         aldehydes with respect to their action on the blood pressure,
         Arch. Int. Pharmacodyn., 102, 65-84

    Zaitsev, A. N. & Rakhmanina, N. L. (1974) Toxic properties of
         phenylethanol and cinnamic alcohol derivatives, Vopr. Pitan.,
         5, 48-53 (in Russian)

    Zaitsev, A. N. & Maganova, N. B. (1975) Embryotoxic effects of some
         aromatizers for food products, Vopr. Pitan., 3, 64-68 (in

    See Also:
       Toxicological Abbreviations
       Cinnamaldehyde (FAO Nutrition Meetings Report Series 44a)
       CINNAMALDEHYDE (JECFA Evaluation)