SUCROSE ESTERS OF FATTY ACIDS AND MONOGLYCERIDES
These substances have been evaluated for acceptable daily intake
for man (ADI) by the Joint FAO/WHO Expert Committee on Food Additives
in 1969, 1973 and 1976 (see Annex I, Refs. 19, 32 and 40).
Toxicological monographs were issued in 1969, 1973 and 1976 (see Annex
I, Refs. 20, 33 and 41).
Since the previous evaluation, additional data have become
available and are summarized and discussed in the following monograph
Sucrose-monostearate was hydrolysed by mucosal homogenates of the
rat small intestine (about 10% in 10 minutes), and by homogenates of
rat liver (about 40% in 4 hours). Blood esterases were inactive
(Shigeoka, et al., 1979).
In vitro techniques, utilizing the everted sac of the rat
intestine showed that the greater part of the U-14C sucrose
monostearate was transferred to the serosal side, but most of the
transferred activity was due to sucrose produced by hydrolyse. Little
of the unchanged sucrose monostearate is transferred to the serosal
side but appears to be accumulated in the tissue (Shigeoka, et al.,
Intestinal absorption of the esters through the mainline
lymphatic system was studied in rats, administered either U-14C
sucrose (*SMS) I-14C monostearate (SM*S) or U-14C sucrose (14C-SE)
orally. 24 hours after administration of the test substance, 14C was
measured in the lymph. About 20% 14C from SM*S was received in the
lymph, whereas in the case of *SMS and 14C-SE, less than 2% of the
14C was received in the lymph (Shigeoka et al., 1979).
Sucrose monopalmitate is hydrolysed by artificial pancreatic
juice in the presence of taurocholate, mucosal homogenates of the rat
small intestine (about 30% in 10 minutes), and by homogenates of rat
liver (about 40% in 4 hours). Some hydrolysis occurs in the presence
of blood esterase: however, the rate is extremely slow compared to the
other enzyme systems (Shigeoka et al., 1979).
In everted rat intestine preparations, sucrose-1-14C-palmitate
was incubated for one hour and the radioactivity measured in mucosal
and serosal fluids and in whole tissue. At the end of incubation, the
radioactivity of the mucosal ester had decreased by about 50%, while
only about 1% of the unchanged ester had transferred to the serosal
side (Shigeoka et al., 1979).
The amount of the ester transferred to the lymph after oral
administration was about 36% of the administered dose, suggesting that
some ester had transferred to the lymph without being hydrolysed. No
unchanged ester was found in portal and femoral blood (Shigeoka et
Rats were dosed orally with sucrose 1-14C monopalmitate
(SM*P), 1-14C Palmitic Acid (*PA), 250 mg/kg bw. 120 hours after
administration of the test substance, the secretion of 14C from the
SM*P dosed rats in urine, faeces and expired air (CO2) was 36%, 34%
and 37%, and from the *PA dosed rats, 2.5%, 16% and 50% respectively.
Most of the excretion occurred in the first 24 hours of the test. 14C
label in the fatty tissue was 30-70 times that in blood. It was
estimated that 15-20% of the 14C administered accumulated in fatty
tissues (Shigeoka et al., 1979).
The gastrointestinal absorption of sucrose mono-oleate was
determined in young adult male rats fed various mixtures of the
triolein: sucrose mono-oleate. The animals were distributed into
groups of 10 according to body weight. After one week's adaptation to
the diet, the food consumption was recorded and the faeces were
collected for each animal during the succeeding 10 days. Fatty acid
analysis was performed on the feed and faeces, and this was used to
determine the coefficient of absorbability for sucrose mono-oleate. It
was found to be almost completely absorbed (Mattson, 1972).
LARD AND TALLOW SUCROSE ESTERS
Adult male rats of the Charles River CD strain were given, either
by oral intubation or by i.p. injection, a solution of [14C] sucrose
tallowate in propylene glycol in a single dose of 5, 50 or 100 mg/kg
of bw. On the average, 5% of the oral dose of [14C] sucrose tallowate
appeared in the urine and 11% in the faeces within 96 hours. 61.5% of
the [14C] was recovered in the expired air. The administration of
[14C] sucrose in similar experiments resulted in radioactive
recoveries which approximated those found in the studies of sucrose
tallowate. In the single i.p. injection studies of [14C] sucrose
tallowate 61% and 19% of the activity was recovered in the urine and
in expired air, respectively, within 19 hours, while negligible
amounts appeared in the faeces (Daniel et al., 1979).
In another study, a group of nine adult male rats [14C] sucrose
tallowate was administered via intubation daily at a dose of 100 mg/kg
of body weight for 21 days. Groups of three animals were killed on
days 7, 14 and 21, and hepatic and adipose tissue were removed and
analysed for radioactivity.
There was no evidence of progressive accumulation of sucrose
tallowate in either the live or adipose tissues. The results were
comparable to those in which sucrose [14C] was administered to rats
for seven days (Daniel et al., 1979).
OBSERVATIONS IN MAN
Three human volunteers were given 1 g of sucrose tallowate in a
mixture of butter and cream cheese, and 24-hour urines were collected
and analysed for sucrose. In addition, each volunteer was given a
solution of 10 g of sucrose in 100 ml of water and urine collections
and analysis were performed as stated above. Urinary analysis for
sucrose showed the presence of 6, 12 and 13 ppm of sucrose in the
dietary study and 7, 15 and 24 ppm of sucrose in the liquid study.
These data suggest that the sucrose tallow esters were rapidly
hydrolysed in and almost completely absorbed from the gastrointestinal
tract and that very little accumulated in the hepatic and adipose
tissues when the esters were administered orally to rats. Since minute
amounts of sucrose appeared in the human urinalysis studies, this too
suggested that, like the rat, the esters were rapidly hydrolysed and
absorbed in the human volunteers (Daniel et al., 1979).
Sucrose esters from beef tallow were provided in the diet to
groups of four male and four female pure bred beagle dogs at
concentrations of 3000, 10 000 or 30 000 ppm for 26 weeks. An
additional group received an identical diet with the exception of the
sucrose ester and acted as the control. Body weight changes, food
intake and water consumption were not affected by the administration
of the ester. The animals in the two highest dosage groups exhibited
periods of soft faeces during the study. The ophthalmic and
haematologic examinations, the urinalysis, the organ weights and
macroscopic examinations revealed no adverse effects which could be
attributed to the intake of the sucrose esters. The blood chemistry
studies showed that the majority of the parameters measured in the
treated animals were within acceptable limits. However, there was a
compound-related increase in plasma alanine amino-transferase in some
of the treated animals. The histopathological examinations were
unremarkable, except that the kidneys of all the female dogs contained
moderate amounts of fat. However, this effect was not related to the
amount of sucrose ester in the diet (Virgo, 1979).
Groups each of 30 SC-JCL homogenous, four-week-old rats, evenly
divided by sex, were maintained at a diet containing 0.0, 0.3, 1.0 or
3% sucrose ester of tallow for 18 months. Body weight changes,
survival, food and compound consumption and food efficiency were
monitored through the experiment. No compound-related effects were
reported. Some changes were noticed in the haematological parameters,
serum biochemistries, organ weights, and urinalysis. However, none of
these effects could be attributed to the administration of the sucrose
ester. Histopathological evaluations were performed on all surviving
animals at the end of the study, and no compound-related, toxic and/or
carcinogenic lesion were found (Kotani, 1974).
MIXED PALMITIC AND STEARIC ACID ESTERS OF SUCROSE
Groups of three male and female beagle dogs received in their
diet sucrose esters of mixed stearic and palmitic acids at
concentrations of 0.3%, 1% or 3.0% daily for 26 weeks. A separate
group of three male and female dogs maintained on diet alone served as
control. During the entire study, the group mean daily intake of the
esters was 102, 345 and 1091 mg/kg in male dogs, and 104, 367 and
1139 mg/kg in female dogs in the three corresponding treatment groups.
No animal died during the study. The plasma glucose levels at 13 weeks
were significantly elevated. However, this effect was dependent
neither on the dose, nor on the length of the study, and thus, could
not be attributed to the administration of the ester. The body
weights, food/water consumption, clinical chemistry, haematology, and
urinalysis were essentially within normal ranges. Gross and
microscopical examinations of tissues and major organs revealed no
significant changes that could be attributed to the ingestion of the
esters (Chesterman et al., 1979).
Metabolic studies have been reported in a number of sucrose
esters, namely sucrose monostearate, sucrose monopalmitate, sucrose
mono-oleate and lard and tallow sucrose esters. In the rat, it is
apparent that the sucrose esters are hydrolysed in the mucosal
epithelium cells before intestinal absorption. This observation is
also supported by the in vitro studies in which rapid hydrolysis of
the esters occurs in the presence of mucosal homogenates of the
intestine, and only slow hydrolysis in the presence of liver
preparations, and negligible hydrolysis by pancreatic juice in the
presence of taurocholate. Studies with humans fed sucrose tallowates,
also indicate that they are absorbed from the GI tract.
There is no evidence of progressive accumulation of the esters or
metabolites, in either experimental animals or man.
A short-term feeding study in the dog (26 weeks), with either
sucrose esters of beef tallow, or sucrose esters of mixed stearic and
palmitic acids, showed no adverse effects related to administration of
the test compound.
The no-effect level was established in the rat at 500 mg/kg bw
and because these substances are hydrolysed in the gut to normal food
constituents, a lower safety factor was used to calculate the ADI.
Level causing no toxicological effect
Rat: 10 000 ppm (1%) in the diet equivalent to 500 mg/kg bw.
Estimate of acceptable daily intake for man
0-10 mg/kg bw.
Chesterman, H., Heywood, R., Allen, T. R., Street, A. E., Read R. &
Gapinath, C. Sucrose ester of mixed stearic and palmitic acid
dietary study in beagle dogs. Unpublished report from Huntingdon
Research Centre, submitted by Ryoto Company Limited, Tokyo,
Daniel, J. W., Marshall, C. J., Jones, H. F. & Snodin, D. J. The
metabolism of beef tallow sucrose esters in rat and man. Fd.
Cosmet. Toxicol., 17, 19-21, 1979
Kotani, S., Imahori, A., Tiba, S. & Shiobara, S. Chronic toxicological
evaluation of DK-Ester-F-110 (sucrose fatty acid ester).
Unpublished report from Juntendo University - Public Hygiene
Laboratory, submitted by Dai-Ichi Kogyo Seiyaku Co., Kyoto,
Mattson, F. & Nolen, G. Absorbability by rats of compounds containing
from one to eight ester groups. J. Nutr., 102, 1171-1175,
Shigeoka, T., Katsuki, M., Izawa, O. & Kitazawa, K. Metabolic study on
sucrose esters of stearic and palmitic acid in rats. Unpublished
report by Mitsubishi-Kosei Institute of Toxicological and
Environmental Sciences, Tokyo, Japan, 1979
Virgo, D. M., Ashby, R., Cummins, H. A., Hepworth, P. L. & Finn,
J. P. Sucrose esters from beef tallow: toxicity in dietary
administration to beagle dogs for 26 weeks. Unpublished report by
Life Science Research, submitted by Tate & Lyle Limited, Reading,
Berkshire, England, 1979