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


    LINALYL ACETATE

    90 per cent. and 96 per cent.

    Chemical name            3,7-Dimethyl-1,6-octadien-3-yl acetate

    Empirical formula        C12H20O2

    Structural formula

            (CH3)2C=CHCH2C=CHCH2C(CH3)(OOCCH3)CH=CH2

    Molecular weight         196.29

    Definition               Linalyl acetate, 90 per cent. contains not
                             less than 90 per cent. of esters, calculated
                             as C12H20O2
                             Linalyl acetate, 96 per cent. contains not
                             less than 96 per cent. of esters, calculated
                             as C12H20O2.

    Description              Linalyl acetate occurs in bergamot,
                             petitgrain, and other oils.  It may be
                             prepared by acetylation and fractionation of
                             Brazilian Bois de Rose Oil, and it may also
                             be prepared synthetically. It is a colour
                             less to slightly yellow liquid having a
                             pleasant floral odour.

    Biological Data

    Biochemical aspects

         This ester is probably hydrolysed to linalol and acetic acid, the
    former being subsequently converted to geraniol and its metabolites
    1,5-dimethyl-1,5-hexadien-1,6-dicarboxylic acid and
    7-carboxy-5-methylocto-6-enoic acid (Patty, 1963).

    Acute toxicity

                                                                     

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

    Mouse        oral        13 360            Jenner et al., 1964

    Rat          oral        14 550            Jenner et al., 1964
                                                                     

         Rat. In a 12-week feeding study on 15 males and 15 females,
    using mixed esters, retardation of growth of female rats occurred at a
    level of 24.3 mg/kg/day (Oser, 1967).

    Long-term studies

         None available.

    Comments

         Despite the absence of precise knowledge of the metabolic fate of
    this ester, evaluation is possible from the additional animal data.
    Biochemical and metabolic studies are needed.

    EVALUATION

    Estimate of acceptable daily intake for man

                                       mg/kg body-weight

         Conditional acceptance             0-0.25

    Further work required

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

    REFERENCES

    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

    Patty, F. A. (1963) Industrial hygiene & Toxicology, Vol. II,
    Interscience, London and New York

                   

    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
       Linalyl acetate (ICSC)
       LINALYL ACETATE (JECFA Evaluation)