ETHYL-L-LACTATE

    Explanation

         Ethyl-L-lactate was evaluated at the 1967, 1979 and 1980 Joint
    Meetings of the FAO/WHO Expert Committee on Food Additives (see Annex
    I, Refs. 14, 51 and 54). A temporary non-specified acceptable daily
    intake for man was established. The additional work required by 1982,
    an in vivo hydrolysis study, has become available and is summarized
    in this monograph.

    BIOLOGICAL DATA

    BIOCHEMICAL ASPECTS

         Substantial evidence has accumulated that simple esters readily
    undergo enzymatic hydrolysis into their component acids and alcohols
    (FEMA, 1974; Longland et al., 1977; Grundschober, 1977). It can be
    presumed that ethyl lactate is readily hydrolysed in the body to ethyl
    alcohol and lactic acid, both of which are common food constituents
    (Fassett, 1963).

         Aqueous solutions of ethyl-L-lactate, containing 1 mg of
    ester/ml, were incubated at 37°C in a 0.05 N phosphate buffer, pH 7.5,
    with or without pancreatin or a porcine small intestinal mucosa
    preparation. The chemical hydrolysis of ethyl-L-lactate was found to
    be less than 2% during 2 hours; with pancreatin less than 7% was
    hydrolysed in 1 hour and 7-9% in 2 hours; with the intestinal mucosa
    preparation these figures were 48-56% and 73-86%, respectively
    (Leegwater & van Straten, 1979). Thus it is likely that ethyl lactate
    is readily hydrolysed in the body to ethyl alcohol and L(+) lactic
    acid, both of which are common food constituents.

         The metabolic fate of ethyl alcohol is well known (FEMA, 1974)
    and lactic acid is, of course, a normal and essential intermediate in
    human metabolism (Oser, 1965). The metabolism of lactic acid has been
    studied extensively, both in humans and in other mammals (Informatics,
    Inc., 1975; FEMA, 1977).

         Three groups of 4 fasted, anaesthetized rats in which the
    oesophagus and a side branch of the portal vein were cannulated
    received approximately 1 ml of either a 10% (0.84 mol/1) of
    ethyl-L-lactate in water, a solution of 0.84 mol/l Li-L-lactate and
    0.84 mol/l ethanol in water or water. Blood samples were drawn at 0,
    5, 20 and 40 minutes after the administration of the test solutions.
    The pattern of absorption of ethyl-L-lactate, varied widely with peak
    plasma concentrations of 0.03 to 1.14 mmol/l appearing from 5 to 40
    minutes after dosing. Ethanol and lactate concentrations after the
    administration of ethyl-L-lactate were generally higher than plasma

    ethyl-L-lactate concentration and tended to increase with time in all
    animals except one. This animal showed peak plasma concentrations of
    L-lactate and ethanol which correlated with that of ethyl-L-lactate.

         In an in vitro study ethyl-L-lactate was added to rat plasma at
    a concentration of 100 ppm (0.01%) (0.85 mmol/1). The plasma was then
    incubated at room temperature and analysed for ethanol and lactate
    after 0 and 60 minutes. Eighty per cent. of the ethyl-L-lactate was
    hydrolysed (Falke et al., 1981).

         Under the conditions of this study, ethyl-L-lactate would appear
    to be partially absorbed unhydrolysed from the gastrointestinal tract
    of fasted rats. However, a quantitative estimate of the fraction of
    ethyl-L-lactate absorbed prior to hydrolysis is not possible due to
    the hydrolysis of this flavour in the rat plasma. It should be noted
    that a relatively high dose level was used which would tend to promote
    rapid absorption especially in fasted animals. Smaller doses in non-
    fasting animals would tend to promote slower absorption, thus a
    greater degree of hydrolysis in the gastrointestinal tract.

    TOXICOLOGICAL STUDIES

    Acute toxicity

         None available.

    Short-term studies

    Rat

         Ethyl lactate was reportedly a good energy source and enhanced
    growth in a group of 8 male weanling rats fed a diet containing 5% of
    this ester (approximately equivalent to 5 g/kg bw) over a period of 12
    days. One of 8 animals died during the course of the experiment (there
    was no indication of the cause of death). No adverse effects were
    observed in the surviving animals (Yoshida et al., 1971).

    Long-term studies

    None available.

    Comments

         Recent in vivo and in vitro studies indicated that
    ethyl-L-lactate was hydrolysed to ethyl alcohol and lactic acid mainly
    prior to absorption. The temporary status of the ADI was removed and
    ethyl-L-lactate was included in the group ADI for lactic acid as "not
    specified".

    EVALUATION

    Estimate of acceptable daily intake for man

    Group ADI for lactic acid: "ADI not specified".*

              

    *    The statement "ADI not specified" means that, on the basis of the
         available data (toxicological, biochemical, and other), the total
         daily intake of the substance, arising from its use or uses at the
         levels necessary to achieve the desired effect and from its
         acceptable background in food, does not, in the opinion of the
         Committee, represent a hazard to health. For this reason, and for
         the reasons stated in individual evaluations, the establishment
         of an acceptable daily intake (ADI) in mg/kg bw is not deemed
         necessary.

    REFERENCES

    Falke, H. E., Bosland, M. C. & Van den Berg, F. (1981) Study on the
          in vivo absorption and hydrolysis of ethyl-L-lactate in the
         rat gastrointestinal tract. Unpublished report from TNO, Zeist
         submitted to WHO by C. V. Chemie Combinatie, Amsterdam C.C.A.,
         Gorchem, The Netherlands

    Fassett, D. W. (1963) Toxicology. In: Patty, F. A. ed. Industrial
         hygiene and toxicology, vol. 2, 2nd rev, New York, London,
         Wiley Interscience

    FEMA (1974) Scientific literature review of aliphatic primary
         alcohols, aldehydes, esters, and acids in flavor usage, published
         by the National Information Services under Contract with the Food
         and Drug Administration

    FEMA (1977) Scientific literature review of propylene glycol, glycerol
         and related substances in flavor usage, published by the National
         Information Services under Contract with the Food and Drug
         Administration

    Grundschober, F. (1977) Toxicological assessment of flavouring esters,
         Toxicology, 8, 387-390

    Informatics, Inc. (1975) Scientific literature reviews on generally
         recognized as safe (GRAS) food ingredients. Lactic acid, US Food
         and Drug Administration, Washington, D.C.

    Leegwater, D. C. & van Straten, S. (1979) In vitro study on the
         hydrolysis of ethyl-L-lactate by pancreatin and an intestinal
         mucosa preparation. Unpublished report from TNO, Zeist, submitted
         to the World Health Organization by C.V. Chemie Combinatie,
         Amsterdam C.C.A., Gorchem, The Netherlands

    Longland, R. C., Shilling, W. H. & Gangolli, S. D. (1977) The
         hydrolysis of flavouring esters by artificial gastrointestinal
         juices and rat tissue preparations, Toxicology, 8, 197-204

    Oser, B. L. (1965) Physiological chemistry, McGraw-Hill Book Company

    Yoshida, M., Ikumo, H. & Suzuki, O. (1971) Evaluation of available
         energy of aliphatic chemicals by rats: an application of bioassay
         of energy to monogastric animal, Agr. Biol. Chem., 35(8),
         1208-1215
    

    See Also:
       Toxicological Abbreviations