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
Geneva
1972
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
PHOSPHATED DISTARCH PHOSPHATE
Biological data
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
0.4 per cent. P.
Biochemical aspects
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 unmodified
starch.
Short-term Studies
Groups of 10 male and 10 female rats received in their diet 0, 25 and
50 per cent. of modified starch (0.3 per cent. P) for 8 weeks. There
were no detectable adverse effects on body-weight. Faecal water
content appeared to be higher in animals fed the 50 per cent. 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
per cent. level in male rats but there was no consistent effect on
females at any level tested (de Groot & Spanjers, 1970).
Dog
Groups of 3 male and 3 female beagles were given daily for 90 days
gelatine capsules containing 50, 250 and 1250 mg modified starch/kg
body-weight. 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 & gay, 1963b).
Man
Twelve volunteers consumed on each of 4 successive days 60 g of a
phosphated distarch phosphate with 0.35 per cent. 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 al., 1971).
Long-term studies
Rat
Groups of 30 male and 30 female rats were fed a modified starch at
dietary levels of 0, 5, 10 and 30 per cent. 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
reveal 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
histopathological examination has not yet been completed (de
Knecht-van Eekelen et al., 1971).
Reproduction studies
Rat
A three generation study was performed using 5 males and 10 females
for the P generation and 10 males and 20 females of the F1b and F2b
to produce successive generations by mating at week 12 and 20 after
weaning. The F3b generation was kept for 3 weeks after weaning and
then sacrificed for histopathological study. The P, F1b and F2b
parents were used for determination of implantation sites. The test
material, fed at 10 per cent. of the diet consisted of starch modified
with sodium trimetaphosphate up to 0.04 per cent. P and sodium
tripolyphosphate up to a total of 0.35 per cent. P. No adverse
effects were noted regarding appearance, behaviour, mortality,
body-weights, fertility, litter size, resorption quotient, weaning
weight of pups or mortality of young. Caecal weights were increased.
In the F3b generation spleen weights in females fed this starch
differed in a statistically significant way from controls. Gross
examination at autopsy did not reveal pathological changes
attributable to ingestion of this starch but histopathology is still
outstanding (Til et al., 1971).
Special studies
Groups of 10 male and 10 female rats were given 0, 25 or 50 per cent.
modified starch in a low residue diet for 7 days. This was followed by
3 further days on a diet containing additional 4 per cent. 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 and 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).
Comments
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 and dog do not reveal any significant adverse
effects even at high dietary levels, if one accepts the available
evidence for the group of modified starches considered that caecal
enlargement without associated histopathological changes is of little
toxicological significance. The long-term and reproduction studies in
the rat did not reveal any significant adverse effects and can be used
for evaluation.
EVALUATION*
Temporarily not limited.**
Further work required by 1973
Histological reports to complete the long-term and reproduction
studies in the rat.
REFERENCES
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., Til, H. P., van der Meulen, H. C. & de
Groot, A. P. (1971) Unpublished report No. R 3392 by Centraal
Instituut voor Voedingsonderzoek
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 Central Instituut voor
Voedingsonderzoek
Til, H. P., Spanjers, M. Th. & de Groot, A. P. (1971) Report No. 3403
of Centraal Instituut voor Voedingsonderzoek
* Includes distarch phosphate prepared using trimetaphosphate of
phosphated distarch phosphate or the sum of both. Subject to limits of
phosphorus load given in the seventh report of the Joint FAO/WHO
Expert Committee on Food Additives, Wld Hlth Org. techn. Rep. Ser.,
281, p. 31
** Except for good manufacturing practice.
See Also:
Toxicological Abbreviations
Phosphated distarch phosphate (FAO Nutrition Meetings Report Series 46a)
Phosphated distarch phosphate (WHO Food Additives Series 5)
Phosphated distarch phosphate (WHO Food Additives Series 17)
PHOSPHATED DISTARCH PHOSPHATE (JECFA Evaluation)