INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
WORLD HEALTH ORGANIZATION
SAFETY EVALUATION OF CERTAIN
FOOD ADDITIVES AND CONTAMINANTS
WHO FOOD ADDITIVES SERIES 40
Prepared by:
The forty-ninth meeting of the Joint FAO/WHO Expert
Committee on Food Additives (JECFA)
World Health Organization, Geneva 1998
SUCROSE ESTERS OF FATTY ACIDS AND SUCROGLYCERIDES
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
3. Comments
4. Evaluation
5. References
1. EXPLANATION
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. BIOLOGICAL DATA
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 1ยด 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).
3. COMMENTS
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.
4. EVALUATION
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.
5. REFERENCES
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)