FAO Nutrition Meetings
    Resort Series No. 44A
    WHO/Food Add./68.33


    Geneva, 21-28 August 1967

    The Eleventh Report of the Joint FAO/WHO Expert Committee on Food
    Additives is published as FAO Nutrition Meetings Report Series,
    1967, No. 44; Wld Hlth Org. techn. Rep. Ser., 1968, 383. This
    Report contains general considerations, including the principles
    adopted for the evaluation, and a summary of the results of the
    evaluations of a number of food additives. Additional information,
    such as biological data and a toxicological evaluation, considered at
    that meeting, is to be found in this document.

    Food and Agriculture Organization of the United Nations
    World Health Organization


    Chemical names                4-Allyl-2-methoxyphenol;

    Empirical formula             C10H12O2

    Structural formula


    Molecular weight              164.21

    Definition                    Eugenol contains not less than 98 per
                                  cent., by volume, of phenols as

    Description                   Eugenol is the main constituent of
                                  carnation, cinnamon leaf and clove oils.
                                  It is obtained from clove oil and other
                                  sources. It is a colourless to pale
                                  yellow liquid, having a strongly
                                  aromatic odour of clove, and a pungent,
                                  spicy taste. It darkens and thickens
                                  upon exposure to air.

    Biological Data

    Biochemical aspects

         Rats and guinea-pigs given 150 mg/animal orally showed inhibition
    of glucosiduronic acid conjugation over 24 hours which was complete in
    stomach, almost complete in duodenum and practically absent in liver.
    Stomach epithelium was desquamated and punctate haemorrhages were seen
    in the pylorus and glandular region. Incubation of slices of stomach,
    duodenum or liver with 0.025 eugenol inhibited 75 per cent. of
    glucosiduronic acid conjugation, indicating interference with
    mucopoly-saccharide formation in tissues with possible gastric ulcer
    formation (Hartiala et al., 1966).

    Acute toxicity


    Animal         Route      LD50               References

    Mouse          oral       3000               Jenner et al., 1964

    Rat            oral       1930-2680          Sober et al., 1950;
                                                 Jenner et al., 1964

                   s.c.       5000(LD)           Binet, 1896

                   i.p.       800-1000(LD)       Binet, 1896

    Guinea-pig     oral       2130               Jenner et al., 1964

         Three male and three female rats given 900 mg/kg intragastrically
    daily for 4 days showed gross liver damage (Taylor et al., 1964).

         Single intragastric doses of about 500 mg/kg body-weight in the
    dog resulted in 2 of the 4 animals to which given. 250 mg/kg body-
    weight resulted only in some emesis, and 200 mg/kg was without effect
    (Lauber & Hollander, 1950).

    Short-term studies

         Rat. Twenty male rats were given increasing doses from 1400 to
    4000 mg/kg body-weight for 34 days. There was considerable mortality,
    slight liver enlargement and adrenal enlargnnent. Histology showed
    enlarged liver cells. The forestomach showed severe hyperplasia and
    hyperkeratosis of the stratified squamous epithelium with focal
    ulceration et al., 1965). In a 12-week feeding study on 15 males and
    15 females no adverse effect was noted at 79.3 mg/kg body weight per
    day (Oser, 1967).  In another study, groups of 10 males and 10 females
    were fed diets containing 0, 0.1 and 1.0 per cent. eugenol for 19
    weeks without any adverse effect on growth rate, haematology, organ
    weights and histology of major tissues (Hagan et al., 1967).

    Long-term studies

         None available.


         There is only scanty information available on the metabolism. 
    High doses are hepatoxic to dogs and rats but the short-term studies
    permit evaluation.  Metabolic studies are needed.


    Level causing no toxicological effect

         Rat. 1 per cent. (= 10 000 ppm) in the diet, equivalent to 500
    mg/kg body-weight/day.

    Estimate of acceptble daily intake for man

                                       mg/kg body-weight

         Conditional acceptance               0-5

    Further work required

         Biochemical and metabolic studies and long-term studies,
    including emphasis on the effects on the gastric epithelium and the


    Binet, P. (1896) Rev.méd. Suisse rom., 15, 449

    Hagan, E. C. Jenner, P. M., Jones, W. I., Fitzhugh, O. G., Long, E.
    L., Brouwer, J. G. & Webb, W. K. (1965) Toxicol. appl. Pharmacol.,
    7, 18

    Hagan, E. C., Hansen, W. H., Fitzhugh, O. G., Jenner, P. M., Jones, W.
    I, Taylor, J. M., Long, E. L., Nelson, A. A. & Brouwer, J. B. (1967)

    Hartiala, K. J. W., Pulkinien, M. & Ball, P. (1966) Nature (Lond.),
    210, 739

    Jenner, P. M., Hagan, E.C., Taylor, J. M., Cook, E. L, & Fitzhugh, O.
    G. (1964) Fd Cosmet. Toxicol., 2, 327

    Lauber, F. U. & Hollander, F. (1950) Gastroenterology, 15, 481

    Oser, B. L. (1967) Unpublished report

    Sober, H. A., Hollander, F. & Sober, E. K. (1950) Proc. Soc. exp.
    Biol. Med., 73, 148

    Taylor, J. M., Jenner, P. M. & Jones, W. I. (1964) Toxicol. appl.
    Pharmacol., 6, 378

    See Also:
       Toxicological Abbreviations
       Eugenol (WHO Food Additives Series 14)
       Eugenol (WHO Food Additives Series 17)
       EUGENOL (JECFA Evaluation)
       Eugenol (IARC Summary & Evaluation, Volume 36, 1985)