evaluation of certain food additives - libdoc.who.int - World Health ...

The Committee had previously evaluated low-range sucrose esters of fatty
acids, which principally include mono-, di- and tri-esters, at its thirteenth,
seventeenth, twentieth, twenty-fourth, thirty-fifth, thirty-ninth, forty-fourth
and forty-ninth meetings (Annex 1, references 19, 32, 41, 53, 88, 101, 116
and 131). At the forty-ninth meeting, the Committee established a group ADI
of 0–30 mg/kg bw for sucrose esters of fatty acids and sucroglycerides on the
basis of potential laxative effects in humans.
For the present evaluation of SOE type I and type II, the Committee considered
the available data on the safety of SOE type I and type II in view of the
Committee’s previous evaluation of low-range sucrose esters of fatty acids.
Toxicological data
The Committee considered studies of the absorption, distribution, metabolism
and elimination (ADME) of components of SOE type I—i.e. tetra-,
hexa- and octa-esters of fatty acids, each separately radiolabelled in both the
fatty acid and sucrose moieties. These studies indicated that the tetra-, hexaand
octa-esters of sucrose with stearic acid were very slowly hydrolysed prior
to intestinal absorption of the hydrolysis products, but only the tetra-ester was
hydrolysed and absorbed to any appreciable extent. These data were consistent
with pharmacokinetic data on mono-, di- and tri-esters of sucrose with
stearic and palmitic acids, which were reviewed at the forty-fourth meeting.
Small amounts of mono-esters were absorbed intact, but the di- and tri-esters
were not. Although specific ADME data for SOE type II were not available,
their metabolic fate can be predicted by the demonstrated inverse relationship
between hydrolysis and the degree of esterification of sucrose esters of fatty
acids.
Toxicological studies, including a 28-day range-finding study and a combined
12-month toxicity and 2-year carcinogenicity study, were available for
SOE type I fed to rats at dietary concentrations of up to 50 000 mg/kg (equal
to 2370 mg/kg bw per day in males and 2800 mg/kg bw per day in females
in the toxicity study; equal to 2120 mg/kg bw per day in males and 2420 mg/
kg bw per day in females in the carcinogenicity study). In these studies, no
significant toxicological or tumorigenic effects were reported. The NOEL
from the 12-month toxicity study was 2370 mg/kg bw per day, the highest
dose tested. The NOEL from the 2-year carcinogenicity study was 2120 mg/
kg bw per day, the highest dose tested.
No studies of reproductive or developmental toxicity were available for SOE
type I or type II. However, in a two-generation reproductive and developmental
toxicity study of sucrose polyester (a mixture of 8.2% hexa-, 33%
hepta- and 58% octa-esters of edible-grade fatty acids with sucrose) fed to
rats at up to 10% of their diet, no adverse effects on reproductive or developmental
parameters were reported.
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