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


    METHYL ANTHRANILATE

    Chemical name            Methyl 2-aminobenzoate

    Empirical formula        C8H9NO2

    Structural formula

    

    Molecular weight         151.17

    Definition               Methyl anthranilate contains not less than 98
                             per cent. C8H9NO2.

    Description              Methyl anthranilate is found in neroli oil
                             and in citrus and other oils. It is prepared
                             synthetically by esterification of
                             anthranilic acid. It is a colourless to pale
                             yellow liquid with a bluish fluorescence. It
                             has a grape-like odour.

    Biological Data

    Biochemical aspects

         This ester is probably hydrolysed and the anthranilate excreted
    mostly as o-aminobenzoyl glucuronide (Charconnet-Harding et al., 1953) 
    Some anthranilic acid is excreted unchanged, while other reported
    metabolites include o-aminohippuric acid, 5-hydroxyanthranilic acid
    and anthranoylanthranilic acid (Williams, 1959).

    Acute toxicity

                                                                      

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

    Mouse          oral     3900           Jenner et al., 1964

    Rat            oral     2910           Jenner et al., 1964

    Guinea-pig     oral     2780           Jenner et al., 1964,

    Rat            oral     3000           Dow Chemical Company, 1967

    Guinea-pig     oral     4000           Dow Chemical Company, 1967
                                                                      

    Short-term studies

         Rat.  Groups of 10 male and 10 female rats were fed diets
    containing 0, 0.1 and 1.0 per cent. ester for 13 weeks without adverse
    effect on weight gain, organ weights or histology of major organs
    (Hagan et al., 1967). In another study on groups of 10 males and 10
    females fed 0, 0.3 and 1.0. per cent., no adverse effect was noted at
    0.3 per cent., but at 1.0 per cent. there were statistically
    significant increases in liver and kidney weights of male rats, with
    renal histologic changes (Dow Chemical Company, 1967).

    Long-term studies

         None available.

    Comments

         Evaluation is based on the short-term studies and the probable
    metabolic fate.

    EVALUATION

    Level Causing No Toxicological Effect

         Rat. 3000 ppm in the diet, equivalent to 150 mg/kg/day.

    Estimate of acceptable daily intake for man

                                       mg/kg body-weight

         Conditional acceptance              0-1.5

    Further work required

         Biochemical, metabolic and long-term tests, including
    carcinogenicity are required.

    REFERENCES

    Charconnet-Harding, F., Dalgliesh, C.E. & Neuberger, A. (1953)
    Biochem. J., 53, 513

    Dow Chemical Company (1967) Unpublished report

    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., 3, 327

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

    See Also:
       Toxicological Abbreviations
       Methyl anthranilate (WHO Food Additives Series 14)
       METHYL ANTHRANILATE (JECFA Evaluation)