Prepared by:
          The forty-ninth meeting of the Joint FAO/WHO Expert
          Committee on Food Additives (JECFA)

        World Health Organization, Geneva 1998


    First draft prepared by
    Ms Elizabeth Vavasour,
    Chemical Health Hazard Assessment Division
    Bureau of Chemical Safety
    Food Directorate, Health Protection Branch
    Health Canada, Ottawa, Ontario, Canada

        1.  Explanation
        2.  Biological data
            2.3 Observations in humans
        4.  Evaluation
        5.  References


        Sucrose esters of fatty acids and/or sucroglycerides were reviewed
    by the Committee at its thirteenth, seventeenth, twentieth, twenty-
    fourth, thirty-fifth, thirty-ninth and forty-fourth meetings (Annex I,
    references 19, 32, 41, 53, 88, 101 and 116). At the forty-fourth
    meeting, the NOEL from a new long-term toxicity study in rats was used
    as the basis for the ADI. The material used in this study contained no
    mono- or diglycerides and the highest dose tested was 2000 mg/kg bw
    per day. Because the results from a human tolerance study raised some
    concerns about potential laxative effects and abdominal symptoms, a
    temporary group ADI for sucrose esters of fatty acids and
    sucroglycerides was established on the basis of the long-term toxicity
    study in rats to which a safety factor of 100 was applied. The results
    of a well-designed and well-conducted tolerance study in humans were
    requested for review in 1997.


    2.3  Observations in Humans

        Human volunteers participated in an oral tolerance study in which
    they were given S-1170, a preparation of sucrose esters of fatty acids
    containing mono-, di- and tri-esters (57%, 28% and 10%, respectively)
    of stearic and palmitic (70:30) acids. The study was conducted on an
    in-patient basis, using a double-blind, cross-over design. Study
    conditions were closely controlled with respect to hours of waking and
    sleeping, food and water consumption, smoking and intake of alcohol,
    caffeine and medications. Ten men and ten women, 21-35 years of age,
    consumed a serving of bread which contained 0.75 g S-1170 or control
    bread, twice daily for 5 days. After a 6-day interval, treatments were
    reversed. In addition to the 5 days of treatment, the subjects were
    monitored for 2 days prior to initiation of treatment and for 2 days
    following treatment. During the study, subjects recorded subjective
    symptoms and frequency and appearance of their faeces. Blood pressure,
    pulse, breathing rate, body temperature, body weight and a standard
    set of haematological, clinical chemistry and urinalysis parameters

    were measured on the first day of the study prior to administration of
    the test substance and at the end of the recovery period on day 7,
    approximately 1 days after the final dose. Medical examinations (no
    description was provided) were conducted on each subject daily prior
    to administration of the test substance and from day 1 to day 7,
    during both the control and treatment periods.

        During the treatment period, male subjects received a mean daily
    dose of 27 mg/kg bw, while female subjects received a dose of 29 mg/kg
    bw. Some abdominal symptoms were noted in a few subjects, which did
    not appear to be related to treatment. Frequency of faecal excretion
    over the five-day test period did not differ for control or treatment
    periods in either the male or female subjects. Faecal consistency
    rated as "muddy" or "watery" was noted only as an isolated occurrence
    in a few subjects either during the treatment or control periods.
    "Soft" faeces lasting for 1 to 4 days were observed in several
    subjects, but with one exception, the same subjects were affected
    during treatment and control periods. The remaining parameters were
    measured at the end of the recovery period rather than at the end of
    treatment and the statistics performed were not appropriate for
    comparing effects of control diet to treated diet. Consequently, no
    conclusion could be reached as to the effect of treatment on these
    parameters (Mitsubishi-Kagaku Foods Corporation, 1996).


        The results from the present study indicated an absence of effects
    of sucrose esters of fatty acids on faecal frequency and consistency
    and related abdominal symptoms in men and women ingesting a divided
    daily dose of 1.5 g sucrose esters of fatty acids (equal to 27 and 29
    mg/kg bw per day, respectively) for five days. In the previous human
    tolerance study, doses which exceeded 1 g as a single dose, or a
    divided dose of 2 g for five days, induced laxation and related
    abdominal symptoms. While the new study addressed the deficiencies in
    study design noted previously, i.e. the small number of subjects and
    the lack of proper controls, only a single dose level was used, which
    was below that previously associated with gastrointestinal
    disturbance. Consequently, it was not possible to confirm whether the
    effects observed previously were the result of treatment with sucrose
    esters of fatty acids.


        The NOEL of 2000 mg/kg bw per day from the long-term study on rats
    combined with a safety factor of 50 would allow for an ADI of 0-40
    mg/kg bw. The lower safety factor was considered appropriate for
    sucrose esters of fatty acids since these compounds are hydrolysed to
    normal dietary constituents in the gastrointestinal tract prior to
    absorption. However, the potential for sucrose esters of fatty acids
    to induce laxative effects at doses exceeding 30 mg/kg bw per day
    cannot be dismissed on the basis of the available human tolerance
    studies. Consequently, a group ADI of 0-30 mg/kg bw for the sucrose
    ester content of sucrose esters of fatty acids and sucroglycerieds was

    allocated on the basis of the new human study without the application
    of a safety factor.


    Mitsubishi-Kagaku Foods Corporation (1996) Study of sucrose esters of
    fatty acids: laxative study of S-1170. Unpublished report dated March
    29, 1996 (Submitted to JECFA by Mitsubishi Chemical Corporation,
    Tokyo, Japan).


    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 15)
       Sucrose esters of fatty acids and sucroglycerides (WHO Food Additives Series 35)