Toxicological evaluation of some food
additives including anticaking agents,
antimicrobials, antioxidants, emulsifiers
and thickening agents
WHO FOOD ADDITIVES SERIES NO. 5
The evaluations contained in this publication
were prepared by the Joint FAO/WHO Expert
Committee on Food Additives which met in Geneva,
25 June - 4 July 19731
World Health Organization
1 Seventeenth Report of the Joint FAO/WHO Expert Committee on
Food Additives, Wld Hlth Org. techn. Rep. Ser., 1974, No. 539;
FAO Nutrition Meetings Report Series, 1974, No. 53.
LACTIC ACID AND ITS AMMONIUM, CALCIUM, POTASSIUM AND
These compounds have been evaluated for acceptable daily intake
by the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1,
Ref. No. 13) in 1966.
Since the previous evaluation, additional data have become
available and are summarized and discussed in the following monograph.
The previously published monograph has been revised and is reproduced
in its entirety below.
L(+)-lactate is a normal intermediary of mammalian metabolism. It
arises from glycogen breakdown, from amino acids and from dicarboxylic
acids, e.g. succinate. Some micro-organisms specifically produce
lactic acid as major product of the metabolism; L. delbrueckii
produces L(+)-lactic acid, the physiological isomer, and
L. leichmanii, the D(-)-isomer.
Various groups of rats were killed three hours after the
administration of L(+), D(-) or DL-lactic acid (1700 mg/kg) orally or
by s.c. injection. The L(+)-isomer produced the largest rise in liver
glycogen; 40-95% of the L(+)-lactate absorbed in three hours being
converted; practically none was formed from the D(-)-isomer.
D(-)-lactate produced the highest blood lactate level and 30% of the
amount absorbed was excreted in the urine; no L(+)-lactate was found.
D(-)-lactate was utilized four times more slowly but both D(-) and
L(+)-isomers were absorbed at the same rate from the intestine (Cori &
Cori, 1929). The absorption of sodium DL-lactate from the intestine of
groups of six male and female rats was determined at one, two, three
and four hours after oral feeding of 215 mg/kw bw of material. The
rate of absorption decreased with time and was roughly proportional to
the amount of lactate present in the gut. Slow evacuation of the
stomach limited the rate of absorption in some animals (Cori, 1930).
At blood levels over 200 to 250 mg lactate, rabbits showed excitation,
dyspnoea and tachycardia (Collazo et al., 1933).
After oral administration to a human subject of 1 to 3000 mg
lactate, 20 to 30% was excreted in the urine during 14 hours (Fürth &
When sodium DL-lactate was given i.v. to starving dogs, 7 to 40%
was recovered in the urine, none was found in the faeces (Abramson &
Eggleton, 1927). Rabbits were given orally 600 to 1600 mg/kg bw of
racemic lactic acid. Most animals died within three days. Urinary
excretion varied between 0.26 and 31%. Alkalosis did not affect the
excretion (Fürth & Engel, 1930).
In vitro studies have shown that mammalian tissue produces only
L(+)-lactate although some tissues can oxidize both isomers. Rat liver
tissue used almost entirely L(+) and practically no D(-)-isomer, as
measured by oxygen consumption and carbohydrate synthesis. Rat kidney
tissue used a definitely measurable amount of D(-)-isomer. Grey matter
of rat brain was unable to utilize the D(-)-isomer. L(+)-lactate
stimulated oxygen consumption and CO2 production of all rat tissues;
similarly D(-)-lactate slightly stimulated respiration of liver and
heart but not brain tissue. Similar effects occurred in duck tissue.
Heart tissue is able to utilize both isomers almost equally well.
14C-L(+)-lactate produces 14CO2 more rapidly than D(-)-lactate in
the intact rat although the D(-) form is fairly well metabolized.
After two hours, both isomers are oxidized at equal rates (Brin,
1964). More recent studies have defined the cell sites for
metabolizing the isomers in micro-organisms and higher animals and
identified the pathways in normal animals, cattle with D(-)
lactacidosis and mentally ill patients (Brin, 1964).
L(+)-lactate was oxidized three to five times as rapidly as
D(-)-lactate by duck and rat heart and liver slices and 10 to 20 times
as rapidly by brain slices, using 14C labelled substrate, as shown by
oxygen consumption and 14CO2 production. The D(-)-isomer was used
equally as well as the L(+)-isomer by duck and rat heart slices,
two-thirds as well by brain and one-third as well by duck and rat
liver and duck brain. High utilization of D(-)-isomer requires special
metabolic pathways (Brin et al., 1952).
Animal Route (mg/kg bw)
Rat i.p. (Sod. lactate) 2 000 Rhône-Poulenc, 1965
oral (lactic acid) 3 730 Smyth et al., 1941
Guinea-pig oral 1 810 Smyth et al., 1941
Mouse oral 4 875 Fitzhugh, 1945
Rats have been stated to survive 2000 to 4000 mg/kw bw
administered s.c. Mice were killed by subcutaneous doses of 2000 to
4000 mg/kg bw whether or not alkalosis was present (Fürth & Engel,
1930). In man, accidental intraduodenal administration of 100 ml 33%
lactic acid was fatal within 12 hours (Leschke, 1932). Other workers
quote an adult human maximum tolerated dose of 1530 mg/kg bw (Nazario,
Groups of two animals received daily doses of 1000 and 2000 mg/kg
bw of sodium lactate (as lactic acid) over 14 to 16 days; Body
analyses showed no cumulation (Fürth & Engel, 1930).
Two dogs received 600 to 1600 mg/kg bw of lactic acid orally 42
times during 2.5 months without ill effects (Faust, 1910).
Feeding of 10% lactic acid has been blamed for the development of
polyneuritic crises resembling B1 deficiency on diets rich in
carbohydrates, proteins or fats (Lecoq, 1936).
No animal studies are available.
OBSERVATIONS IN MAN
Forty full-term newborn infants were given a commercial feeding
formula containing 0.4% DL-lactic acid. No effect was observed on the
rate of weight gain, from the second to the fourth week of life
(Jacobs & Christian, 1957).
Healthy babies were fed milk formulae acidified with 0.4 to 0.5%
DL-lactic acid for periods of 10 days, during the first three months
of their life. An increase in the titrable acidity of the urine and
lowering of urinary pH was observed. Babies on "milk rich" formula
(4/5 milk mixture) excreted twice as much acid in the urine as babies
on diets containing less milk and approximately 33% developed
acidosis. Clinical manifestations were: decrease in the rate of body
weight gain and decrease in food consumption. On replacing the
acidified diet with "sweet milk" diet these effects were reversed very
rapidly (Droese & Stolley, 1962).
When 0.35% DL-lactic acid was administered to healthy babies from
the tenth to the twentieth day of life, a threefold increase in the
urinary excretion of the physiological L(+)-lactic acid and a
twelvefold increase in the D(-)-lactic acid was observed. On
withdrawing lactic acid from the diet the level of lactic acid
excreted in the urine returned to normal. Since the racemic mixture
used consisted of 80% of the L(+) and 20% of the D(-) forms it seems
that the metabolism of the D(-) form by the young full-term baby is
more difficult than the L(+) form. The increase in the urinary
excretion of either form of lactic acid indicated that the young
infant cannot utilize lactic acid at a rate which can keep up with
0.35% in the diet. A number of babies could not tolerate lactic acid.
In such cases there was rapid loss of weight, frequent diarrhoea,
reduction of plasma bicarbonate and increased excretion of organic
acids in the urine. All these effects were reversed on withdrawing
lactic acid from the diet (Droese & Stolley, 1965).
Man has consumed fruits, sour milk and other fermented
products containing DL-lactic acid for centuries, apparently
without any adverse effects.
In evaluating lactic acid, emphasis is placed on its well-
established metabolic pathways after normal consumption in man. It is
an important intermediate in carbohydrate metabolism. However, human
studies determining the maximum load of lactate are not available.
There is some evidence that babies in their first three months of life
have difficulties in utilizing small amounts of DL and D(-) lactic
No limit need be set for the acceptable daily intake for man.
Estimate of acceptable daily intake
Neither D(-)-lactic acid nor (DL)-lactic acid should be used in
FURTHER WORK OR INFORMATION
Desirable: Metabolic studies on the utilization of D(-) and
DL-lactic acid in infants.
* See relevant paragraph.
Abramson, H. A. & Eggleton, P. (1927) J. Biol. Chem., 75, 745, 753,
Brin, M. (1964) J. Ass. Food and Drug. Off., 178
Brin, M., Olson, R. E. & Stare, F. J. (1952) J. Biol. Chem., 199, 467
Collazo, J. A., Puyal, J. & Torres, I. (1933) Anales Soc. Esp. Fis,
Quim., 31, 672
Cori, C. F. & Cori, G. T. (1929) J. Biol. Chem., 81, 389
Cori, G. T. (1930) J. Biol. Chem., 87, 13
Droese, W. & Stolley, H. (1962) Dtsch. med. J., 13, 107
Droese, W. & Stolley, H. (1964) Symp. über die Ernäbrung der
Frühgeborenen, Bad Schachen, May 1964, 63-72
Faust, E. S. (1910) Cothener Chem. Z., 34, 57
Fitzhugh, O. G. (1945) Unpublished data, submitted to WHO
Fürth, O. & Engel, P. (1930) Biochem. Z., 228, 381
Jacobs, H. M. & Christian, J. R. (1957) Lancet, 77, 157
Lecoq, M. R. (1936) C.R. Acad. Sci., 202, 1304
Leschke, E. (1932) Munch. Med. Wschr., 79, 1481
Nazario, G. (1951) Rev. Inst. Adolfo Lutz, 11, 141
Rhône-Poulenc (1965) Unpublished report
Smyth, H. F. jr, Seaton, J. & Fischer, L. (1941) J. Ind. Hyg.
Toxicol., 23, 59