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