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




    TOXICOLOGICAL EVALUATION OF SOME
    FLAVOURING SUBSTANCES AND
    NON-NUTRITIVE SWEETENING AGENTS





    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
    1967


    GERANYL ACETATE

    Chemical name            3,7-Dimethyl-2 trans,6-octadienyl acetate

    Empirical formula        C12H20O2

    Structural formula

                                CH3       CH3

                             CH3C=CHCH2CH2C=CHCH2OCOCH3

    Molecular weight         196.29

    Definition               Geranyl acetate contains not less than 90
                             per cent. of total esters, calculated as
                             C12H20O2.

    Description              Geranyl acetate is found in the oils of
                             Daucus carota L., Eucalyptus macarthurii
                             Deane, and other oils. It is obtained from
                             geraniol by ecetylation. It is a colourless
                             liquid, having a pleasant flowery odour.

    Biological Data

    Biochemical aspects

         This ester is probably metabolized to 
    1,5 dimethy-1-1,5-hexadien-1,6-dicarboxylic acid,
    7-carboxy-3-methylocta-6-enoic acid and acetic acid (Williams, 1959).

    Acute toxicity

                                                                       

    Animal       Route       LD50                Reference
                             (mg/kg 
                             body-weight)
                                                                       
    Rat          oral        6330               Jenner et al., 1964
                                                                       

    Short-term studies

         Rat. In a 12-week feeding study on 15 males and 15 females,
    using mixed esters, there was a slight retardation of growth in
    females at a level of 48.4 mg/kg body-weight/day (Oser, 1967). The
    substance was fed to groups of 10 male and 10 female rats at levels of
    0, 0.1 0.25 and 1.0 per cent. in the diet for 17 weeks without
    detection of any adverse effects on major tissues (Hagan et al.,
    1967).

    Comments

         Despite the scanty animal data it is possible to evaluate this
    compound on the basis of its likely metabolic fate and the short-term
    studies. Confirmatory studies are needed.1

    EVALUATION

    Level causing no significant toxicological effect

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

    Estimate of acceptable daily intake for man

                                  mg/kg body-weight

         Conditional acceptance          0-5

    Further work required

         Biochemical and metabolic studies in animals and man and
    long-term studies.1

    REFERENCES

    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)
    Fd Cosmet. Toxicol., 5,(2), 141

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

    Oser, B. L. (1967) Unpublished report

    Willliams, R. T. (1959) Detoxication Mechanisms, Second Edition,
    Chapman & Hall, London


                   

    1 When considering the group of flavouring substances citral, 
    citronellol, linalol, linalyl acetate and geranyl acetate, the
    Committee stressed the urgent need to elucidate the metabolic pathways
    which may be common to these widely distributed substances. They found
    it reasonable to require that one or more of these substances should
    be made the subject of long-term studies. Whether this limitation can
    be made and which substances should be chosen may follow from a
    consideration of the biochemical evidence when this becomes available.
    


    See Also:
       Toxicological Abbreviations
       GERANYL ACETATE (JECFA Evaluation)