Toxicological evaluation of some food
additives including anticaking agents,
antimicrobials, antioxidants, emulsifiers
and thickening agents
WHO FOOD ADDITIVES SERIES NO. 5
The evaluations contained in this publication
were prepared by the Joint FAO/WHO Expert
Committee on Food Additives which met in Geneva,
25 June - 4 July 19731
World Health Organization
Geneva
1974
1 Seventeenth Report of the Joint FAO/WHO Expert Committee on
Food Additives, Wld Hlth Org. techn. Rep. Ser., 1974, No. 539;
FAO Nutrition Meetings Report Series, 1974, No. 53.
HYDROXYPROPYL DISTARCH GLYCEROL
Explanation
Modification is performed by the use of 0.1% epichlorhydrin and
up to 10% propylene oxide. Cross-linkage would be no greater than
expected on modification with 0.1% epichlorhydrin. Substitution by
treatment with 10% propylene oxide would probably add no more than
15-20 ether linkages per 100 glucopyranose units.
BIOLOGICAL DATA
BIOCHEMICAL ASPECTS
The in vitro digestibility of a hydroxypropyl distarch glycerol
(degree of substitution 0.04) by pancreatin and porcine intestinal
mucose was found to be 86% of that of the native starch (Leegwater,
1971).
TOXICOLOGICAL STUDIES
Special studies on reproduction
Groups each of 10 male and 20 female rats were fed the modified
starch at a level of 10% in their diet for a period of three
generations. Rats were mated (P1, F1 and F2) at week 12 and 20
after weaning. Each generation was mated twice and the litter from the
second generation used to produce the next generation. No adverse
effects were noted on fertility, number of pups per litter, body
weight of young, mortality experience or resorption quotient that
could be ascribed to treatment. The average relative caecum weight
(filled) of females of the P and F2 generation was greater than
controls, but empty caecum weight did not differ from controls. The
relative caecum weight (filled and empty) of males of the F1
generation did not differ from controls. Growth of the F3b generation
maintained on test diet for three weeks was normal. Relative organ
weights were comparable to control, with the exception of decreased
thyroid weight and distinctly increased caecal weight (both filled and
empty) in male pups, and increased empty caecal weight in female pups.
Gross examination of organs at autopsy did not show any compound-
related changes. Gross and microscopic examination of F3b rats did
not show any compound-related changes (Til et al., 1971b).
Short-term studies
Rat
Groups of 10 male and 10 female rats were fed for eight weeks on
a diet containing 25 or 50% modified starch. Although the body weights
of males at the higher level tested were slightly lower than those of
the controls, the differences were not statistically significant. The
faecal dry matter content was increased at both test levels in both
sexes and there was considerable diarrhoea at the 50% level in both
sexes. Slight diarrhoea occurred at the 25% level in both sexes.
Caecal weights were increased in a dose-related manner at all levels
in all test groups but no histological abnormalities could be detected
in the caeca (de Groot & Spanjers, 1970).
Groups of 25 male and 25 female rats were fed for 13 weeks on a
diet containing 1 and 5% of modified starch or 5% of native starch.
The general appearance and behaviour of test rats was comparable with
the controls. One male and one female rat died at the lower test
level. Growth, feed consumption, body weight, haematology at one and
three months, urinalysis at one and three months, gross and
histopathological findings were comparable in all groups (Knapp,
1967a).
In another experiment, groups of 10 male and 10 female rats were
fed for 90 days diets containing 0, 5, 10 or 30% modified starch. No
differences between test and control animals were noted with regard to
appearance, behaviour, growth, food consumption, haematology, serum
chemistry urinalysis. No definite diarrhoea occurred at any test
level. The amounts of dry matter in the faeces did not vary
significantly between controls and treated animals. Only at the 30%
level were the caecal weights increased in both sexes. Gross and
histopathology were otherwise unremarkable in all groups.
Histopathology of the enlarged caeca showed no recognizable
abnormality (de Knecht-van Eekelen et al., 1970).
Dog
Three groups of four male and four female beagle dogs were given
in their diet 1 and 5% of modified starch or 5% of native starch for
13 weeks. Haematological studies, blood sugar, blood urea, serum GPT
and alkaline phosphatase as well as urinalysis were comparable for all
groups. Appearance and behaviour were normal. Body weight changes were
unrelated to the administration of the test substance. Gross and
histopathology showed no consistent abnormalities. Organ weights of
thyroid, heart, liver, spleen, kidneys, adrenals and testes showed no
test-related changes (Knapp, 1967b).
Pig
Groups of eight Pitman-Moore miniature pigs were weaned at three
days of age, and were fed formula diets containing 5.4% unmodified
starch or 4.9% hydroxypropyl distarch glycerol for 25 days. Growth was
normal during the test period. At termination of the study,
biochemical analyses of blood (haemoglobin) and serum (cholesterol,
triglyceride, calcium, phosphorus, alkaline phosphatase, urea
nitrogen, total protein, albumin and globulin) were similar for test
and control animals. Relative organ weight as well as carcass
composition (water, fat, protein, ash, Ca, PO4, Na, Mg) and liver
composition (water, fat, protein and ash), were similar for test and
control animals (Anderson et al., 1973).
Long-term studies
Groups of 30 male and 30 female rats were fed for 104 weeks
modified starch at 0, 5, 10 and 30% of their diet. No differences were
noted between test and control animals with regard to appearance,
behaviour, food consumption, haematology, serum chemistry and
urinalysis. The mortality of females at the 30% level was slightly
higher. The growth rate was slightly reduced for both sexes at the 30%
level when compared with controls. Caecal weight was increased at 30%
in males and at 10% and 30% in females. Microscopic examination
revealed no noticeable changes in the caecal wall. Renal calcification
accompanied by focal hyperplasia of the pelvic epithelium was more
marked in males fed 30% of the test compound than in control males. No
distinct compound-related gross or microscopic changes were
encountered in any of the organs examined (Til et al., 1971a).
OBSERVATIONS IN MAN
Twelve volunteers consumed 60 g modified starch on each of four
successive days. No adverse effects were noticed and no abnormalities
occurred as regards frequency and amount of faeces or faecal water and
lactic acid content (Pieters et al., 1971). œ
Comments:
The feeding studies with rats, dogs and pigs show that the
modified starch is well utilized. The studies with radio-labelled
hydroxypropyl starch provide some information in the rat on the
metabolic fate of the hydroxypropyl moiety. Several short-term studies
in the rat and dog show no adverse effects even at high dietary
levels. The available evidence for the group of modified starches
considered indicates that caecal enlargement without associated
histopathological changes is without toxicological significance. The
long-term and reproduction studies in the rat indicate no significant
adverse effects and may be used for evaluation.
EVALUATION
Estimate of acceptable daily intake for man
Not limited.*
REFERENCES
Anderson, T. A. et al. (1973) Unpublished data submitted to Corn
Refiners Ass., Inc.
de Groot, A. P. & Spanjers, M. Th. (1970) Unpublished report
No. R 3096 by Centraal Instituut voor Voedingsonderzoek
Knapp, W. A. jr (1967a) Report of Hazleton Laboratories Inc.,
submitted by the International Latex and Chemical Corporation
Knapp, W. A. jr (1967b) Report of Hazleton Laboratories Inc.,
28 February submitted by the International Latex and Chemical
Corporation
de Knecht-van Eekelen, A., Willems, M. & de Groot, A. P. (1970)
Unpublished report No. R 3093 by Centraal Instituut voor
Voedingsonderzoek
Leegwater. D. C. (1971) Unpublished report No. R 3431 by Centraal
Instituut voor Voedingsonderzoek
Pieters, J. J. L., van Staveren, W. A. & Brinkhuis, B. G. A. M. (1971)
Unpublished report No. R 3433 by Centraal Instituut voor
Voedingsonderzoek
Til, H. P. et al. (1971a) Unpublished report No. R 3363 by Centraal
Instituut voor Voedingsonderzoek
Til, H. P., Spanjers, M. Th. & de Groot, A. P. (1971b) Report No. 3403
of Centraal Instituut voor Voedingsonderzoek, submitted to WHO
* See relevant paragraph in the seventeenth report, pages 10-11.
See Also:
Toxicological Abbreviations
Hydroxypropyl distarch glycerol (FAO Nutrition Meetings Report Series 46a)
Hydroxypropyl distarch glycerol (WHO Food Additives Series 1)
Hydroxypropyl distarch glycerol (WHO Food Additives Series 17)
HYDROXYPROPYL DISTARCH GLYCEROL (JECFA Evaluation)