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
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.
PHOSPHATED DISTARCH PHOSPHATE
These modified starches are prepared by the combined use of
sodium tripolyphosphate and sodium trimetaphosphate which results in
cross-linking and esterification of starch chains. The overall extent
of modification is small, the residual phosphate being of the order of
The in vitro digestibility of this modified starch by
pancreatic amylase (Kohn & Kay, 1963) or by pancreatin and porcine
intestinal mucosa (Leegwater, 1971) was somewhat reduced compared with
Groups of 10 male and 10 female rats were given 0, 25, or 50%
modified starch in a low residue diet for seven days. This was
followed by three further days on a diet containing additional 4%
cellulose. The body weights of test animals were slightly reduced in
both sexes in a dose-related manner but the actual changes were small.
No diarrhoea was noted although faecal dry matter was somewhat higher
in test animals compared with controls. The addition of cellulose to
the diet had no adverse effect. No histological abnormality of the
enlarged caeca was noted (de Groot & Spanjers, 1970).
Special studies on reproduction
Groups of 10 males and 20 females were fed for three generations
10% of starch modified with sodium trimetaphosphate up to 0.01% P and
sodium tripolyphosphate up to a total of 0.35% P. Rats were mated (P,
F1 and F2) at week 12 and 20 after weaning. The second litter
of each generation was used to produce the next generation. The
F3b-generation was kept for three weeks after weaning and then
sacrificed for histopathological study. The P, F1b and F2b parents
were used for counting implantation sites. No adverse effects were
noted regarding appearance, behaviour, body weights, fertility, litter
size, resorption quotient, weights of pups and mortality. Caecal
weights were not increased except the filled caecum weight of F1
parent males. The spleen weight of F3b females was increased. Gross
and macroscopical examination did not reveal pathological changes
attributable to the ingestion of this starch (Til et al., 1971).
Groups of 10 male and 10 female rats received in their diet 0, 25
and 50% of modified starch (0.3% P) for eight weeks. There were no
detectable adverse effects on body weight. Faecal water content
appeared to be higher in animals fed the 50% test level but the
results were too variable to allow any definite conclusions.
Production of faeces appeared to be unaffected by this modification
when compared with controls. No diarrhoea occurred at any test level.
Caecal weight was only slightly increased at the 25% level in male
rats but there was no consistent effect on females at any level tested
(de Groot & Spanjers, 1970).
Groups of 10 male and 10 female rats were fed on a diet
containing 10% rising to 35% of phosphated distarch phosphate for a
total of 60 days. Female rats showed a consistent reduced weight gain
throughout the test. Although four test and two control animals died
during the test these incidents were regarded as unrelated to the test
substance. All animals behaved normally. Haematological examination
and urinalysis were normal and comparable in the various groups. The
absolute liver weights of male rats were lower for the test group than
for controls and the absolute kidney weight were lower for both sexes
but these findings were not associated with any gross or
histopathological changes (Kohn et al., 1964).
Groups of 25 male and 25 female rats were fed diets containing
0.2, 1.0 and 5.0% modified or unmodified starch for 90 days. Eleven
controls and three test animals died from intercurrent disease. There
were no obvious gross or histopathological changes attributable to the
test substance. Organ weights and haematological examination (days 45
and 90) were normal in both groups. Pooled urinalysis was comparable
for all three groups (Kohn et al., 1964).
Groups of three male and three female beagles were given daily
for 90 days gelatine capsules containing 50, 250 and 1250 mg modified
starch/kg bw. No adverse effects were observed as judged by behaviour,
body weight changes, mortality, haematological studies, blood
chemistry, urinalysis, liver function tests, organ weights, gross and
histopathological findings (Cervenka & Kay, 1963).
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 5.6% phosphated distarch phosphate 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).
Groups of 30 male and 30 female rats were fed a modified starch
at dietary levels of 0, 5, 10 and 30% for 104 weeks. No adverse
effects were noted on general appearance, behaviour, mortality
experience or food intake. Growth rate and food efficiency were
similar to controls. Haematology, serum chemistry and urinalysis
revealed no consistent changes related to the administration of the
test substance. Relative organ weights were comparable with controls
except for significantly decreased spleen weight in males and
significantly increased spleen and kidney weights in females at the
highest levels fed. These changes were not associated with any gross
pathological findings. Caecal weights were normal at all test levels.
There was no obvious evidence of any carcinogenic effect. The
histological examination did not reveal any distinct compound-related
changes. The incidence of nephrocalcinosis accompanied by hyperplasia
of the pelvic epithelium was slightly higher in test animals than in
controls (de Knecht-Van Eekelen et al., 1971).
OBSERVATIONS IN MAN
Twelve volunteers consumed on each of four successive days 60 g
of a phosphated distarch phosphate with 0.35% introduced P. No adverse
effects were noticed. No changes occurred as regards frequency and
amount of faeces of faecal water and lactic acid content (Pieters et
The extent of the modification is small. The metabolic behaviour
of the phosphate moieties has not been studied. The available short-
term studies in the rat, dog and pig do not reveal any significant
adverse effects even at high dietary levels. The available evidence
for modified starches as a group, indicates that caecal enlargement
without associated histopathological changes is without toxicological
significance. The long-term and reproduction studies in the rat did
not reveal any significant adverse effects and can be used for
Estimate of acceptable daily intake for man
Anderson, T. A. et al. (1973) Unpublished data submitted to Corn
Refiners Ass., Inc.
Cervenka, H. & Kay, J. H. (1963) Unpublished report of Industrial
Biotest Laboratories submitted by Corn Products Co.
de Groot, A. P. & Spanjers, M. Th. (1970) Unpublished report No. R
3096 by Centraal Instituut voor Voedingsonderzoek
de Knecht-van Eekelen, A. et al. (1971) Unpublished report No. R 3392
by Centraal Instituut veer Voedingsonderzoek
Kohn, F. E., Kay, J. H. & Calandra, J. C. (1964) Unpublished report
submitted by Corn Products Co.
Kohn, F. E. & Kay, J. H. (1963) Unpublished report by Industrial
Biotest Laboratories submitted by Corn Products Co.
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
Til, H. P., Spanjers, M. Th. & de Groot, A. P. (1971) Report No. 3403
of Centraal Instituut voor Voedingsonderzoek
* See relevant paragraph in the seventeenth report, pages 10-11.
Includes distarch phosphate prepared using trimetaphosphate or
phosphated distarch phosphate or the sum of both. Subject to limits of