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


    d-CARVONE and 1-CARVONE

    Chemical names           d-2-Methyl-5-isopropenyl-2-cyclohexenone;
                             and 1-2-Methyl-5-isopropenyl-2-cyclohexenone

    Empirical formula        C10H14O

    Structural formula

    

    Molecular weight         150.22

    Definition               d-Carvone and 1-Carvone contain not less
                             than 95 per cent. C10H14O.

    Descriptions             d-Carvone is usually prepared by fractional
                             distillation from caraway oil. It may be
                             prepared in a similar manner from either
                             dillseed oil or dillweed oil, but this type
                             differs in odour and flavour from that
                             dervied from caraway oil. It is a colourless
                             to light yellow liquid having an odour of
                             caraway.

                             1-Carvone occurs in several essential oils.
                             it may be isolated from spearmint oil or
                             synthesized commercially from D-limonene.
                             It is a colourless to pale straw-coloured
                             liquid having an odour of spearmint.

    Biological Data

    Biochemical aspects

         The rabbit metabolized this ketone to
    1,5-dimethyl-1,5-hexadien-1,6-dicarboxylic acid and a carbinol in
    which one ethylenic linkage is saturated and the keto group reduced
    (Fischer & Bielig, 1940).

    Acute toxicity

                                                                       

    Animal         Route       LD50             References
                               (mg/kg 
                              body-weight)
                                                                       

    Rat            oral       1640              Jenner et al., 1964

    Guinea-pig     oral        766              Jenner et al., 1964
                                                                       

    Short-term studies

         Rat. Groups of 5 male and 5 female rats were kept on diets
    containing 0, 0.1 and 1.0 per cent. of carvone for 28 weeks. The group
    at the highest level was sacrificed after 16 weeks, when growth
    retardation and testicular atrophy were noted. No adverse effects were
    seen at the 0.1 per cent. level (Hagan et al., 1967).

         A one-year study was performed or groups of 5 male and 5 female
    rats fed a diet containing 0 or 0.25 per cent. carvone. No adverse
    effects were noted on body-weight gain, organ weight of major organs
    or in the histology of the main organs and tissues, including testes
    (Hagan et al., 1967).

    Long-term studies

         None available.

    Comments

         Depite the scanty metabolic data the evaluation is based on
    short-term studies. Further biochemical studies are required.

    EVALUATION

    Level causing no toxicological effect

         Rat: 0.25 per cent. (= 2500 ppm) in the diet, equivalent to 125
    mg/kg body-weight/day.

    Estimate of acceptable daily intake for man

                                       mg/kg body-weight

              Conditional acceptance        0-1.25

    Further work required

         Biochemical and metabolic studies in animals and man.

    REFERENCES

    Fischer, F. G. & Bielig, H. J. (1940) Hoppe-Seylers Z., 266, 73

    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, 372
    

    See Also:
       Toxicological Abbreviations
       Carvone, d- and carvone, 1- (WHO Food Additives Series 14)