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.
STEAROYL LACTYLIC ACID, CALCIUM AND SODIUM SALTS
These substances have been evaluated for acceptable daily intake
by the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1,
Ref. No. 20 and 27) in 1969 and 1971.
The previously published monographs have been revised and are
reproduced in their entirety below.
In vitro hydrolysis with lipase proceeded readily to form
stearic and lactic acid (Hodge, 1961). Rats fed either salt of this
acid excreted only traces of lactate in the faecal fat with good
utilization of stearic acid and calcium (Hodge, 1961).
Experiments comparing the metabolism of mixed stearic acid and
14C-lactic acid with calcium 14C-stearoyl lactylate (lactic acid
labelled) showed 58% excretion of the 14C of the physical mixture and
60% of the 14C-moiety as 14CO2 within 24 hours. There was no
difference in C14-distribution and excretion between the two groups.
Thus lactate derived from calcium stearoyl lactylate is metabolized
normally (Hodge, 1955).
Animal Route (mg/kg bw) Reference
Rat oral over 25 000 Schuler & Thornton, 1952
Groups of five male rats received CaSL at levels of 0.5, 2.0 and
12.5% in their diet for 43 days. No animal died but the weights of
liver, heart, brain, stomach and testes were increased at the 12.5%
level, relative liver weight was increased at the 2% level and growth
was reduced at the 2 and 12.5% level (Hodge, 1953).
In a paired feeding study, groups of 10 rats were given 0 or 5%
CaSL for 27 days. The test groups showed slightly lower food
efficiency. Liver weight of the test group was increased but the
histology was normal except for a slight increase in glycogen. In
another paired feeding study, groups of 10 male and 10 female rats
received either 0.5% CaSL or 12.5% of a 41:59 mixture of calcium
lactate and stearic acid. The test groups grew a little better but had
raised liver weight. Histology of livers and kidneys was normal in all
groups and X-rays of femurs were comparable (Hodge, 1953a).
Groups of five male rats received either 41:59 mixtures of
calcium lactate and stearic acid for 32 days or 41:59 mixtures of
sodium lactate and stearic acid for 52 days at 0, 0.5, 2 and 10% of
the diet. At the 10% level the sodium lactate group had a slightly
reduced growth, but the organ weights of brain, stomach, spleen, lung
and testes were raised. Histology was normal. Some organ weights were
reduced at the 10% level in the calcium lactate group but histology
was normal (Hodge, 1953).
Groups of eight male and eight female rats received either 3.5%
cellulose fibre or 3.5% stearoyl lactylate in their diet for 90 days.
There was no difference between groups in growth rate, food
consumption, faecal fat elimination, gross and histopathology (Schuler
et al., 1952).
Groups of 10 male and 10 female rats received NaSL at 0, 0.5, 5
and 12.5% in their diet for 102 days. Growth was reduced at the
highest level. No abnormalities compared with controls were seen as
regards urinalysis, haematology, and faecal excretion. At the highest
test level the weights of liver, brain, stomach and spleen were
increased but gross and histopathology were normal (Hodge, 1953).
In a similar experiment on groups of 10 male and 10 female rats,
CaSL was fed in the diet at levels of 0.5, 5 and 12.5% for 98 days.
Growth was slightly retarded at 5% and significantly reduced at 12.5%
and the relative weights of liver, stomach, heart, spleen and brain
were increased at 12.5%. No histological abnormalities were seen in
kidneys, brain, lung, spleen and liver, but at the 12.5% level
lipogranulomata were detected in the adipose tissue. No increase in
stainable liver fat was seen. Urinalysis and blood morphology were
normal. Radiological studies of femurs were normal and showed that the
additional dietary calcium had no effect on body load (Hodge, 1953a).
Groups of 12 rats were fed for four weeks diets containing 0 or
5% CaSL or a mixture of calcium lactate, stearic acid and lactic acid.
The animals on CaSL grew best with better food efficiency and better
calcium deposition in the bones than in controls. The liver weights of
the CaSL group were greater than those of controls or the group on the
mixed compounds. No other pathological changes were seen (Wisconsin
Alumni Research Foundation, 1955).
Twenty male rats received 0 or 5% NaSL for 28 days and 30 male
rats received 0 or 5% CaSL for 32 days. Relative liver weights were
normal compared with controls in the CaSL group but raised slightly in
the NaSL group. Groups of five rats were sacrificed at 32, 60, 90 and
140 days. Liver weights were normal in the NaSL group after 90 days
Further experiments were undertaken to elucidate the effect of
different levels of calcium and sodium on relative liver weights as
well as the effect of the fat level of the diet on relative liver
weights. The relative liver weights became normal when rats returned
to stock diets. When diets contained physical mixtures of stearic
acid, lactic acid and calcium carbonate, they produced comparable
liver weights (Hodge, 1954). Similar tests using 5% CaSL, 4.3%
stearoyl lactylic acid or 3% stearic acid in 24 groups of five male
rats each at varying levels of dietary fat showed slightly reduced
body weight in the groups receiving CaSL or stearoyl lactylic acid.
Mortality was not affected by treatment. The relative liver weights
were comparable for all groups and liver histology revealed no
abnormalities (Hodge, 1959). In a similar experiment four groups of 32
male rats each were fed diets containing 0 or 5% CaSL, 3.11% calcium
stearate or 3.2% sodium stearate. The group on CaSL grew better than
all other groups. The relative liver weights of the controls were
higher than all other groups (C. J. Patterson Co., 1956). The chemical
composition of the liver was determined in groups of 10 male and 10
female rats given 0 or 5% CaSL for one month. Only slight changes in
glycogen, protein and lipid content were noted, lipid and protein
being slightly increased compared with controls (Hodge, 1955a).
Groups of 25 rats received diets containing 0, 0.1, 1.0, 2, 3, 4,
5 and 7.5% of calcium stearoyl lactylate for one month. At the two
highest levels there was growth retardation with relative liver weight
increase. Groups of five male rats were given diets containing either
15% lard or 10% lard plus 5% calcium stearoyl lactylate for 30 days.
The test group grew at a lower rate but relative liver weights were
less than in the controls. Groups of 10 rats received diets containing
5% of calcium palmityl lactylate or calcium oleyl lactylate for 30
days. All test groups grew slower and had markedly raised relative
liver weights compared with 5% calcium stearoyl lactylate. Kidney
weights were normal for all groups and histological examination of
liver, kidneys and fatty tissues revealed no abnormalities in any of
these groups (Hodge, 1956).
The appearance of "lipogranulomata" and the increased relative
liver weight are related to the excessive intake of abnormal
proportions of long-chain fatty acids. The balance between saturated
and unsaturated fats (S:U ratio) in the human diet is about 0.6 if
the diet contains 30 to 40% fat. Rats fed diets containing 35 to
50% saturated fatty acid products (palmitic acid, stearic acid
ethylstearate, monoglycerides and acetylated monoglycerides of
hydrogenated lard) develop localized fat necrosis with formation of
"lipogranulomata". The condition is preventable by simultaneous
feeding of corn oil and reversible by a return to normal diet (Cox
& De Eds, 1958; Herting & Crain, 1958; Ambrose et al., 1958).
Groups of five rats were maintained for periods up to six months
on diets containing varying levels of calcium stearyl dilactylate
(3 to 25%) and stearoyl lactylate acid (8 to 22%). The total fat
content was 20%. The outcome depended on the S:U ratio. The added fats
were chosen to give ratios from 0.6 to 4.4. Growth was depressed with
increasing percentage of calcium stearoyl lactylate at 16% and higher
levels and with 14% and above for the acid. Mortality was high at
levels of 20% and above. Relative liver weights were normal at S:U
ratios of 0.6 (17% fat plus 3% calcium stearoyl lactylate or 17% fat
plus 2.6% stearoyl lactylate acid) but rose with higher ratios.
Lipogranulomata appeared at ratio values beyond 1.4. The iodine
number of depot fats reflected the variation in S:U ratio of the
diet. Restoration to the basal ration containing 20% fat caused
disappearance of lipogranulomata in four to six months. No
histopathological abnormalities were seen (Hodge et al., 1964). In a
repeat experiment with 40 male and 40 female rats fed 25% calcium
stearoyl lactylate or 18% stearoyl lactylate acid in their diet, all
animals developed severe lipogranulomata with high mortality. Recovery
was rapid if animals were placed on basal diet containing 20% fat
(half corn oil half lard). Growth rate recovered and any deaths
occurring were unrelated to the diet (Hodge, 1960).
One male and three female beagles were fed a diet containing 7.5%
calcium stearoyl lactylate; another group of one male and three
females served as controls. After two years, no noteworthy differences
were observed between the two groups. Urinalysis and haematological
findings remained normal. No gross or microscopic changes were found
attributable to administration of calcium stearoyl lactylate. Liver
weights were within normal range; nor did the livers differ in
moisture, protein, lipids, ash or glycogen content. Other organ
weights were also normal. No adverse effects were observed in one dog
receiving sodium stearoyl lactylate in his diet for one month at a
level of 7.5%, then increased to 12.5% for two weeks and to 15% for
another month. No changes occurred in the blood; organ weights and the
microscopic appearance of the tissues were normal (Hodge, 1955b).
Adequate biochemical studies have revealed no differences between
the metabolisms of 14C-labelled lactic acid when present as stearoyl
ester and when mixed with an equivalent amount of stearic acid. Since
all the lactic acid derived from stearoyl lactylate enters the
metabolic pool after complete hydrolysis of the ester, it is
justifiable to consider conventional long-term studies as unnecessary.
Extensive short-term studies in rats have given variable and
inconsistent results as regards levels producing no-effect on growth
or relative liver weight. The 2% level has been taken to be the
no-effect level for the rat. The dog appears to be a less sensitive
species. It would be desirable to confirm that man metabolizes
stearoyl lactylate similarly to other species.
Level causing no toxicological effect
Rat: 20 000 ppm (2%) in the diet equivalent to 1000 mg/kg bw.
Estimate of acceptable daily intake for man
0-20 mg/kg bw.
FURTHER WORK OR INFORMATION
Desirable: Studies confirming that this compound is metabolized
by man in the same way as by other species.
Ambrose, A. M., Robbins, D. J. & Cox, A. J. (1958) Fed. Res., 23, 536
Cox, A. J. & De Eds, F. (1958) Amer. J. Path., 34, 263
Herting, D. C. & Crain, R. C. (1958) Proc. Soc. exp. Biol. (N.Y.), 98,
Hodge, H. C. (1953) Unpublished reported dated 2 April 1953, submitted
by C. J. Patterson Co.
Hodge, H. C. (1953a) Unpublished reported dated 18 July 1953,
submitted by C. J. Patterson Co.
Hodge, H. C. (1954) Unpublished report submitted by C. J. Patterson
Hodge, H. C. (1955) Unpublished report dated 30 June 1955 submitted by
C. J. Patterson Co.
Hodge, H. C. (1955a) Unpublished report dated 28 May 1955 submitted by
C. J. Patterson Co.
Hodge, H. C. (1955b) Unpublished report dated 17 June 1955 submitted
by C. J. Patterson Co.
Hodge, H. C. (1956) Unpublished report submitted by C. J. Patterson
Hodge, H. C. (1959) Unpublished report submitted by C. J. Patterson
Hodge, H. C. (1960) Unpublished report submitted by C. J. Patterson
Hodge, H. C. (1961) Unpublished report submitted by C. J. Patterson
Hodge, H. C., Maynard, E. A., Downs, W. L. & Panner, B. (1954)
Toxicol. appl. Pharmacol., 6, 350
C. J. Patterson Co. (1956) Unpublished report
Schuler, M. N., Kodras, R., Allebach, H. K. B. & Gilliam, W. S. (1952)
Unpublished report submitted by Midwest Research Institute
Schuler, M. N. & Thornton, M. H. (1952) Unpublished report submitted
by Midwest Research Institute
Wisconsin Alumni Research Foundation (1955) Unpublished report
submitted by J. C. Patterson Co.