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


    ETHYL VANILLIN

    Chemical name                 3-Ethoxy-4-hydroxybenzaldehyde

    Empirical formula             C9H10O3

    Strucutral formula

    

    Molecular weight              166.18

    Description                   Fine, white or slightly yellowish
                                  crystals, having a strong vanilla-like
                                  odour and taste; affected by light.

    Biological Data

    Biochemical aspects

         This ester is probably metabolized to glucuroethyl vanillin and
    ethyl vanillic acid, of which some is conjugated with glucuronic and
    sulfuric acids (Williams, 1959).

    Acute toxicity

                                                                       

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

    Mouse          i.p.       750             Caujolle & Meynier, 1954

    Rat            oral       1590            Sporn, 1960
                                                                       

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

    Rat            oral       >2000           Jenner et al., 1964

    Rat            s.c.       1800 (LD)       Deichmann & Kitzmuller,
                                              1940

    Guinea-pig     i.p.       1140            Caujolle & Meynier, 1954

    Rabbit         oral       3000 (LD)       Deichmann & Kitzmuller,
                                              1940

    Dog            i.v.       760 (LD)        Caujolle & Meynier, 1954
                                                                       

    Short-term studies

         Rat.  Doses of 300 mg/kg body-weight were administered to rats
    i.g. twice weekly for 14 weeks without any adverse effects. In another
    experiment groups of 16 rats were fed 20 mg/kg body-weight/day for 18
    weeks without adverse effect, but 64 mg/kg body-weight/day for 10
    weeks reduced growth rate and caused myocardial, renal, hepatic, lung,
    spleen and stomach injuries (Deichmann & Kitzmuller, 1940). Groups of
    5 male rats were fed 0, 2 and 5 per cent. in their diet for 1 year
    without any adverse effects (Hagan et al., 1967). Sixteen rats were
    given 30 mg weekly for 7 weeks without adverse effect on growth, food
    intake or protein utilization (Sporn, 1960).

    Long-term studies

         Rat. Groups of 12 male and 12 female rats were fed diets
    containing 0, 0.5, 1 and 2 per cent. ethyl vanillin for 2 years
    without any adverse effects on growth, organ weights of major organs,
    haematology and histology of major tissues (Hagan et al., 1967).

    Comments

         Few direct metabolic studies have been carried out on this ether.
    However, the long-term studies in rats permit evaluation. Further
    metabolic studies are desirable.

    EVALUATION

    Level causing no toxicological effect

         Rat. 2 per cent. (= 20 000 ppm) in the diet, equivalent to 1000
    mg/kg body-weight/day.

    Estimate of acceptable daily intake for man

                                       mg/kg body-weight

         Unconditional acceptance            0-10

    REFERENCES

    Caujolle, F. & Meynier, D. (1954) C.r. hebd. Sean. Acadi. Sci.,
    Paris, 238, 2576

    Deichmann, W. & Kitzmuller, K. V. (1940) J. Amer. pharm. Ass., 29,
    425

    Hagan, E. C., Hansen, W. H., Fitzhugh, O. C., Jenner, P. M., Joes,
    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., Cork, E. L. & Fitzhugh, O.
    G. (1964) Fd Cosmet Toxicol ., 2, 327

    Sporn, A. (1960) Igiena (Bucharest), 9, 365

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

    See Also:
       Toxicological Abbreviations
       Ethyl vanillin (WHO Food Additives Series 26)
       Ethyl vanillin (WHO Food Additives Series 35)
       ETHYL VANILLIN (JECFA Evaluation)