FAO Nutrition Meetings
Report Series No. 40A,B,C
TOXICOLOGICAL EVALUATION OF SOME
ANTIMICROBIALS, ANTIOXIDANTS, EMULSIFIERS,
STABILIZERS, FLOUR-TREATMENT AGENTS, ACIDS AND BASES
The content of this document is the result of the deliberations of the
Joint FAO/WHO Expert Committee on Food Additives which met at Rome,
13-20 December, 19651 Geneva, 11-18 October, 19662
1 Ninth Report of the Joint FAO/WHO Expert Committee on Food
Additives, FAO Nutrition Meetings Report Series, 1966 No. 40;
Wld Hlth Org. techn. Rep. Ser., 1966, 339
2 Tenth Report of the Joint FAO/WHO Expert Committee on Food
Additives, FAO Nutrition Meetings Report Series, 1967, in press;
Food and Agriculture Organization of the United Nations
World Health Organization
Chemical name DL-2-hydroxy propionic acid;
DL-1-hydroxyethane carboxylic acid
Empirical formula C3H6O3
CH3 - C - COOH
Molecular weight 90.08
Definition Commercial products contain lactic acid
and water and may contain lactic
anhydride in the more concentrated
solutions. The total acid content,
calculated as C3H6O3 is not less
than 95 per cent. and not more than 105
per cent. of the amount specified.
Description A colourless or yellowish, nearly
odourless liquid with an acid taste.
Use As on acidulant.
L(+)-lactate is a normal intermediary of mammalian metabolism. It
arises from glycogen breakdown, from amino acids and from dicarboxylic
acids, e.g. succinate. Other sources of production are muscular
contractile activity, and liver and blood metabolism. Some
micro-organisms specifically produce lactic acid as main product of
the metabolism; L. delbrueckii produces L(+)-lactic acid, the
physiological isomer, and L.lelchmanii, the D(-)-isomer.
Various groups of rats were killed 3 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 per cent. of the L(+)-lactate absorbed in 3 hours
being converted; practically none were formed from the D(-)-isomer.
D(-)-lactate produced the highest blood lactate level and 30 per cent.
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 6 male and female rats was determined at 1, 2,
3 and 4 hours after oral feeding of 215 mg/kg body-weight 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 200-250 mg per cent.
lactate, rabbits showed excitation, dyspnoea and tachycardia (Collazo
et al., 1933).
After oral administration to a human subject of 1-3000 mg
lactate, 20-30 per cent. was excreted in the urine during 14 hours
(Fürth & Engel, 1930).
When sodium DL-lactate was given i.v. to starving dogs, 7-40 per
cent. was recovered in the urine, none was found in the faeces
(Abramson & Eggleton, 1927). Rabbits ware given orally 600-1600 mg/kg
body-weight of racemic lactic acid. Most animals died within 3 days.
Urinary excretion varied between 0.26 per cent. and 31 per cent.
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 14O2 more rapidly than D(-)-lactate in the
intact rat although the D(-) form is fairly well metabolized. After 2
hours, both isomers are oxidized at equal rates (Brin, 1964). More
recent studies have defined the cell sites for metabolizing the
isomers in microorganisms and higher animals and identified the
pathways in normal animals, cattle with D(-) lactacidosis and mentally
ill patients (Brin, 1964). L(+)-lactate was oxidized 3-5 times as
rapidly as D(-)-lactate by duck and rat heart and liver slices and
10-20 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 LD50 References
Rat i.p. (Sod. lactate) 2 000 Rhône-Poulenc,
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 2000-4000 mg/kg body-weight
administered s.c. Mice were killed by doses of 2000-4000 mg/kg
body-weight whether or not alkalosis was present Fürth & Engel, 1930),
In man, accidental intraduodenal administration of 100 ml 33 per cent.
lactic acid was fatal within 12 hours (Leschke, 1932). Other workers
quote an adult human maximum tolerated dose of 1530 mg/kg body-weight
Bird. Feeding of 10 per cent. lactic acid has been blamed for
the development of polyneuritic crises resembling B1 deficiency on
diets rich in carbohydrates, proteins or fats (Lecoq, 1936).
Rat. Groups of 2 animals received daily doses of 1000 and 2000
mg/kg body-weight of sodium lactate (as lactic acid) over 14-16 days.
Body analyses showed no cumulation (Fürth & Engel, 1930).
Dog. Two dogs received 600-1600 mg/kg body-weight of lactic
acid orally 42 times during 2.5 months without ill effects (Faust,
Infants. Forty full-term newborn infants were given a
commercial feeding formula containing 0.4 per cent. 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 0.4-0.5 per
cent. DL-lactic acid for periods of 10 days, during the first 3 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 per cent. 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 per cent. DL-lactic acid was administered to healthy
babies from the tenth to the twentieth day of life, a three-fold
increase in the urinary excretion of the physiological L(+)-lactic
acid and a twelve-fold 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 per cent. of the L(+) and 20 per cent. 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 per cent. 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).
No animal studies are available.
Man has consumed meat and other items of food containing lactates
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
Lactic acid has a sufficiently acid taste to limit the amount
used in food.
Estimate of acceptable daily intake of L(+)-isomer
No limit need be set for the acceptable daily intake for man of
the L(+)-isomer of lactic acid.
Estimate of acceptable daily intakes for man of D(-)-isomer
Conditional acceptance 0-100
Limitations of use
Neither the D(-) nor DL-Lactic acid should be added to food for
very young infants, except for therapeutic purposes.
For adults the acceptable daily intake of DL-lactic acid is
calculated from the D(-)-lactic acid content.
Further work required
Metabolic studies on the utilization of D(-) and DL-lactate acids
in infants and adults.
Abramson, H. A. & Eggleton, P. (1927) J. Biol. Chem., 75, 745,
Brin, M. (1964) J. Ass. Food and Drug. Off., 178
Brin, M., Olson, R. E. & Stare, F. J. (1952) J. Biol. Chem., 199,
Collazo, J. A., Puyal, J. & Torres, I. (1933) Anales Soc. Esp. Fis.
Quim., 31, 672
Cori, G. T. (1930) J. Biol. Chem., 87, 13
Cori, C. F. & Cori, G. T. (1929) J. Biol. Chem., 51, 389
Droese, W. & Stolley, H. (1962) Dtsch. med. J., 13, 107
Droese, W. & Stolley, H. (1964) Symp. über die Ernährung der
Frühgeborenen, Bad Schachen, May 1964, 63-72
Faust, E S. (1910) Cöthener Chem. Z., 34, 57
Fitzhugh, O. G. (1945) Unpublished data, submitted to WHO
Fürth, O. & Engel, F. (1330) 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