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.
ACETYLATED DISTARCH PHOSPHATE
Modification is usually performed by the use of up to 0.1% of
phosphorus oxychloride and 5% acetic anhydride. Vinyl acetate may be
used as an alternative acetylating agent. Maximum acetylation amounts
usually to 2.5% acetyl groups.
The digestibilities in vitro by pancreatin and porcine mucosal
enzymes of acetylated distarch phosphates, modified to 1.6% and 2.3%
acetyl content, were found to be 93% and 31% respectively of that of
unmodified starch (Leegwater, 1971).
Groups of 10 male and 10 female rats were fed 0, 25 or 50% of two
different modified starches (acetic anhydride and vinylacetate
modified) in a low residue diet for seven days followed by the
additional feeding of 4% cellulose for three days. The body weights of
animals fed 50% modified starch were somewhat lower than those of the
controls. Production of faecal dry matter was increased in the higher
groups and less so at the 25% level. Diarrhoea occurred at the higher
level with both modified starches. The addition of 4% cellulose had no
effect on the severity or frequency of the diarrhoea. At the higher
level there was also some loss of hair in both sexes (de Groot &
A three generation study was performed using groups of 10 males
and 20 females for the P, F1 and F2 generations to produce two
successive litters in each generation by mating at week 12 and 20
after weaning. Ten males and 10 females of the F b generation were
kept for three weeks after weaning and then sacrificed for
histopathological studies. The P, F b and F b parents were used for
determination of implantation sites. The test material fed at 10% of
the diet consisted of a starch modified with 8% acetic anhydride and
0.02% phosphorus oxychloride (D.S. of 0.093) and another starch
modified with 4.5% vinylacetate and 1.2% phosphorus oxychloride (D.S.
of 0.064, 0.043% phosphorus introduced). No adverse effects were noted
in respect of health, behaviour, mortality, growth, fertility, litter
size, resorption quotient, weaning weight or mortality of young.
Caecal weight of parent rats fed the modified starches were not
increased. Gross pathology revealed a slightly decreased thyroid
weight and a slightly increased caecum weight of F3b rats fed the
starch treated with acetic anhydride and phosphorus oxychloride.
Histopathology failed to reveal any treatment-related changes (Til et
Groups of 10 male and 10 female rats were fed 0, 25 and 50% of
two different modified starches (acetic anhydride and vinylacetate
modified) in their diet for eight weeks. Body weights of animals on
the higher test level were somewhat lower than at the 25% level and
also lower than controls in both sexes. However, the differences were
not statistically significant. The faecal water content was variable
and could not be related to dietary dosage levels. Production of
faecal dry matter was increased in both sexes at the higher level
tested and slightly so at the 25% dietary level. The incidence of
diarrhoea was insignificant. A dose-related increase in caecal weight
occurred in both sexes. No histological abnormality of the enlarged
caeca was noted (de Greet & Spanjers, 1970).
Groups of four male and four female pigs were given 0, 35 or 70%
of modified starch in their diet over 14-1/2 weeks. Growth rate and
food consumption were satisfactory. Haematology, blood chemistry and
urinalysis revealed no treatment-related abnormalities. Ophthalmoscopy
showed no abnormalities associated with the test substance. Organ
weight, gross and histopathology revealed no abnormalities in test or
control groups. Three pigs in the higher test group died suddenly at
various intervals during the test without any evidence pointing to the
cause of their death. One pig in the higher test group and another in
the 35% group showed evidence of neurological malfunction. The animal
on 70% test substance died, that on the lower dietary level recovered.
No histological evidence of nervous system involvement was noted in
these two nor in any other animal (Shillam et al., 1971).
A further pig study in which groups of eight pigs were fed 0, 5,
15 and 25% modified starch in the diet for 14 weeks, showed no effect
on growth, food consumption, haematology or biochemistry. One pig died
of unknown cause. No significant abnormalities were found at post
mortem but histology was not performed except in the animal which died
(Shillam et al., 1973).
Groups of 30 male and 30 female rats were fed two different
modified starches (acetic anhydride and vinylacetate modified) at
levels of 0, 5, 10 and 30% in their diet for 104 weeks. Appearance,
behaviour, food consumption and mortality were not adversely affected
nor was diarrhoea observed at any level. Growth was slightly depressed
at the highest dietary level with both modified starches. Haematology,
serum chemistry and urinalysis revealed no effects related to
treatment in any group. There was a dose-related increase in the
caecal weight in both sexes at the 30% level but in males only at the
10% level. All other organ weights showed no treatment-related
changes. No gross or microscopic pathological abnormalities were noted
which could be related to the test substances or which would point to
any carcinogenic effects or to any compound related effects. The caeca
appeared remarkably normal (Til et al., 1971a).
OBSERVATIONS IN MAN
Twelve volunteers consumed on each of four successive days, 60 g
acetylated distarch phosphates of either 1.6% or 2.33% acetyl content.
No abnormalities were observed as regards frequency and amount of
faeces as well as faecal water and lactic acid content. No other
adverse effects were noticed (Pieters et al., 1971).
The feeding studies with rat and pig show that these modified
starches are well utilized. The long-term and reproduction studies in
rats reveal only caecal enlargement. It is appropriate to use these
studies for evaluation.
Estimate of acceptable daily intake for man
* See relevant paragraph in the seventeenth report, pages 10-11.
de Groot, A. P. & Spanjers, M. Th. (1970) Unpublished report No. R
3096 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
Shillam, K. W. G. et al. (1971) Unpublished report No. 3978/71/136 by
Huntingdon Research Centre
Shillam, K. M. G. et al. (1973) Unpublished report No. CRN5/73254 by
Huntingdon Research Centre
Til, H. P. et al. (1971a) Unpublished report No. R 3351 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