SUCROSE ESTERS OF FATTY ACIDS AND MONOGLYCERIDES

    Explanation

         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
    addendum.

    BIOLOGICAL DATA

    SUCROSE MONOSTEARATE

    BIOCHEMICAL ASPECTS

         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.,
    1979).

         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

    BIOCHEMICAL ASPECTS

         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
    al., 1979).

         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).

    SUCROSE MONO-OLEATE

    BIOCHEMICAL ASPECTS

         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

    BIOCHEMICAL ASPECTS

         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).

    TOXICOLOGICAL STUDIES

    Short-term studies

    Dog

         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).

    Long-term studies

    Rat

         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

    TOXICOLOGICAL STUDIES

    Short-term studies

         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).

    Comments

         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.
    

    EVALUATION

    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.
    

    REFERENCES

    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,
         Japan, 1979

    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,
         Japan, 1974

    Mattson, F. & Nolen, G. Absorbability by rats of compounds containing
         from one to eight ester groups. J. Nutr., 102, 1171-1175,
         1972

    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
    

    See Also:
       Toxicological Abbreviations
       Sucrose esters of fatty acids and sucroglycerides (WHO Food Additives Series 10)
       Sucrose esters of fatty acids and sucroglycerides (WHO Food Additives Series 35)
       Sucrose esters of fatty acids and sucroglycerides (WHO Food Additives Series 40)