WORLD HEALTH ORGANIZATION
WHO Food Additives Series 1972, No. 1
TOXICOLOGICAL EVALUATION OF SOME
ENZYMES, MODIFIED STARCHES AND
CERTAIN OTHER SUBSTANCES
The evaluations contained in this publication were prepared by the
Joint FAO/WHO Expert Committee on Food Additives which met in Rome,
16-24 June 19711
World Health Organization
1 Fifteenth Report of the Joint FAO/WHO Expert Committee on Food
Additives, Wld Hlth Org. techn. Rep. Ser., 1972, No. 488; FAO
Nutrition Meetings Report Series, 1972, No. 50.
The monographs contained in the present volume are also issued by the
Food and Agriculture Organization of the United Nations, Rome, as FAO
Nutrition Meetings Report Series, No. 50A
(c) FAO and WHO 1972
Treatment with epichlorhydrin under akaline conditions up to 0.3 per
cent. tends to produce cross-linking at a rate of one glycerol diether
linkage per 220 - glycopyranose units.
Much evidence in the literature points to etherified starches being
somewhat resistant to enzymic degradation. Probably small fragments
containing the ether linkage will remain and will not be absorbed
readily. Any material absorbed is likely to be excreted by the
kidney. No direct experimental evidence exists for this particular
hypothesis (French, 1960). The metabolic fate of methylglucose is
cited as collateral evidence. Although methylglucose is absorbed by
rats (Sols, 1956) no demethylation is believed to occur (Csaky &
Wilson, 1956) and excretion is essentially quantitative (Csaky &
Glenn, 1957). The in vitro digestibility by amyloglucosidase of
distarch glycerol (0.3 per cent. epichlorhydrin) was shown to be 98.3
per cent. of that of unmodified starch (Kruger, 1970). The caloric
values of two starches treated at levels of 0.07 per cent. and 0.50
per cent. epichlorhydrin were estimated in groups of 10 weanling male
rats by comparing the weight gain obtained after feeding for 28 days a
basal diet supplemented with 3 g of each starch against a
dose-response curve obtained by feeding daily sucrose supplements of
0, 1.5 g, 3 g, 4.5 g and 6 g equivalent to approximately 0, 6, 12, 18
and 24 calories. Distarch glycerols were only slightly lower in
caloric value than unmodified starch, the differences not being
Three groups of 10 male and 10 female rats were fed for 90 days
unmodified starch or starch treated with 0.07 per cent. or 0.50 per
cent. epichlorhydrin at 71 per cent. of their diet. Growth rate,
appearance, behaviour and food intake were similar in all 3 groups.
Haematological investigations showed no abnormalities related to the
feeding of modified starches. Non-protein nitrogen blood levels and
blood sugar levels remained normal in all groups. The weights of all
major organs were normal and no abnormal gross or histopathological
changes related to treatment were seen.
The feeding studies with rats show that the modified starch is well
utilized. The available evidence for the group of modified starches
considered suggests that caecal enlargement without associated
histopathological changes is of little toxicological significance.
The short-term rat study shows no adverse effects at the high dietary
level used. No long-term study on this modified starch is available
and collateral evidence from the long-term and reproduction studies
with hydroxypropyl distarch glycerol, a more highly modified starch,
indicates that the glycerol linkage is causing no adverse effects.
Temporarily not limited.*
Further work required by 1973
Histological report to complete the 2-year rat study on hydroxypropyl
Histological report to complete the reproduction study on
hydroxypropyl distarch glycerol.
Csáky, T. Z. & Wilson, J. E. (1956a) Biochem. Biophys. Acta., 22, 185
Csáky, T. Z. & Glenn, J. E. (1956b) Amer. J. Physiol., 188, 159
French, D. (1960) Unpublished report
Kruger, L. (1970) Unpublished reports Nos 405 & 406 submitted by
National Starch and Chemical Co.
Oser, B. L. (1961) Unpublished report of Food and Drug Research
Laboratories Inc., submitted by National Starch and Chemical Corp.
Sols, A. (1956) Rev. esp. Fisiol., 12, 17
* Except for good manufacturing practice.