PHOSPHATED DISTARCH PHOSPHATE
Explanation
This modified starch was previously evaluated for an ADI for man
by the Joint FAO/WHO Expert Committee on Food Additives in 1969, 1971
and 1973 (see Annex I, Refs. 19, 26 and 29). Toxicological monographs
were published in 1969, 1972 and 1974 (see Annex I, Refs. 20, 27 and
30).
Since the previous evaluation, additional data have become
available and are summarized and discussed in the following monograph.
The previously published monograph has been expanded and is reproduced
in its entirety below.
Introduction
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% phosphorus.
BIOLOGICAL DATA
BIOCHEMICAL ASPECTS
The in vitro digestibility of this modified starch (prepared
from cornstarch) by pancreatic amylase was somewhat reduced compared
with unmodified starch (Kohn & Kay, 1963a). In vitro digestibility
of this modified starch (prepared from potato starch) by pancreatin
and porcine intestinal amylase was also reduced compared with
unmodified starch (Leegwater, 1971). However, in vitro digestibility
and utilization of this modified starch (prepared from milo starch)
was similar to unmodified starch when measured by weight gain (Kohn &
Kay, 1963b).
TOXICOLOGICAL STUDIES
Special studies on reproduction
Groups of 10 male and 20 female rats were fed for 3 generations
10% of starch modified with sodium trimetaphosphate up to 0.01% P and
sodium tripolyphosphate up to a 0.32% P. Rats were mated (P1, F1 and
F2) at weeks 12 and 20 after weaning. The second litter of each
generation was used to produce the next generation. 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
counting implantation sites. No adverse effects were noted regarding
appearance, behaviour, body weight, 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; de Groot et al., 1974).
Special studies
Groups of 10 male and 10 female rats were given 0, 25, or 50%
modified starch in a low residue diet for 7 days. This was followed by
3 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).
Short-term studies
Groups of 10 male and 10 female rats received in their diet
0, 25 and 50% of modified starch (0.3% 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% 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).
Rat
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 4 test and 2 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 weights were lower for both sexes
but these findings were not associated with any gross or
histopathological changes (Kohn et al., 1964a).
Groups of 25 male and 25 female rats were fed diets containing
1.0 and 5.0% modified or unmodified starch for 90 days. Eleven
controls and 3 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 3 groups (Kohn et al., 1964b).
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 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).
Pig
Groups of 8 Pitman-Moore miniature pigs were weaned at 3 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., 1973a, b).
Long-term studies
Rat
Groups of 30 male and 30 female rats were fed this 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.
Histological examination did not reveal any distinct compound-related
changes. The study did not reveal any indication of carcinogenicity.
In comparison with the controls, the males fed the 30% level of the
modified starch showed a slightly increased degree and incidence of
focal hyperplasia of the renal papillary and pelvic epithelium,
accompanied by calcified patches in the underlying tissue. The
hyperplastic and calcified tissues often protruded into the renal
pelvis and were localized most often in the papilla near the junction
of the papillary and pelvic epithelium. This lesion was seen to a
slight or moderate degree in both sexes at most levels including the
controls but was more pronounced and of higher occurrence in males at
the highest dose level (de Knecht-Van Eekelen et al., 1971; de Groot
et al., 1974).
Roe (1979) has conducted an extensive review of this type of
mineral deposition in the renal pelvis of rats and concluded that
pelvic nephrocalcinosis, corticomedullary nephrocalcinosis, acute
tubular nephropathy, and calculus formation are manifestations of
mineral imbalance and are of relatively common occurrence in untreated
laboratory rats (particularly older animals).
OBSERVATIONS IN MAN
Twelve volunteers consumed on each of 4 successive days 60 g of a
phosphated distarch phosphate. No adverse effects were noted. No
changes occurred as regards frequency and amount of faeces or faecal
water and lactic acid content (Pieters et al., 1971).
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, 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 effects, except for a slight increase in
the incidence of renal focal hyperplasia and mineral deposit. This
lesion is considered to be associated with imbalances of Ca/P and Mg
in the diet.
EVALUATION
Estimate of acceptable daily intake for man
Not specified.*
* The statement "ADI not specified" means that, on the basis of the
available data (toxicological, biochemical, and other), the total
daily intake of the substance, arising from its use or uses at
the levels necessary to achieve the desired effect and from its
acceptable background in food, does not, in the opinion of the
Committee, represent a hazard to health. For this reason, and for
the reasons stated in individual evaluations, the establishment
of an acceptable daily intake (ADI) in mg/kg bw is not deemed
necessary.
The ADI includes distarch phosphate prepared using
trimetaphosphate or phosphated distarch phosphate or the sum of both.
Subject to limits of phosphorus load (see monograph on "Phosphoric
acid and phosphate salts").
REFERENCES
Anderson, T. A. et al. (1973a) Unpublished data submitted to Corn
Refiners Ass., Inc.
Anderson, T. A., Filer, L. J., Fomon, S. J., Andersen, D. W.,
Jensen, R. L. & Rogers, R. R. (1973b) Effects of waxy corn starch
modification on growth, serum biochemical values and body
composition of Pitman-Moore miniature pigs, Fd. Cosmet.
Toxicol., 11, 747-754
Cervenka, H. & Kay, J. H. (1963) Subacute oral toxicity of phosphate
starch code number 4822: beagle dogs. Report of Industrial
Biotest Laboratories, Inc., Northbrook, Ill. Submitted by Corn
Products Co., Argo, Ill.
de Groot, A. P. & Spanjers, M. Th. (1970) Observations in rats fed on
diets containing five different chemically modified starches.
Report No. R 3096 by Centraal Instituut voor Voedingsonderzoek,
Zeist, Holland
de Groot, A. P., Til, H. P., Feron, V. J., Van der Meullen, H. C. D. &
Willems, M. I. (1974) Two-year feeding and multigeneration
studies in rats on five chemically modified starches, Fd.
Cosmet. Toxicol., 12, 651-664
de Knecht-van Eekelen, A., Til, H. P., Willems, M. I. & de Groot,
A. P. (1971) Chronic (2-year) feeding study in albino rats with
phosphated distarch phosphate (a chemically modified starch).
Report No. R 3392. Centraal Instituut voor Voedingsonderzoek,
Zeist, Holland
Kohn, F. E. & Kay, J. H. (1963a) The digestion of various starches by
pancreatic amylase. Report of Industrial Biotest Laboratories,
Inc., Northbrook, Ill. Submitted to Corn Products Company, Argo,
Ill.
Kohn, F. E. & Kay, J. H. (1963b) Nutritional assay of starch 4822.
Report of Industrial Biotest Laboratories, Inc., Northbrook, Ill.
Submitted to Corn Products Company, Argo, Ill.
Kohn, F. E., Kay, J. H. & Calandra, J. C. (1964a) 60-day Target organ
study on phosphate starch, code No. 4822. Report of Industrial
Biotest Laboratories, Inc., Northbrook, Ill. Submitted to Corn
Products Company, Argo, Ill.
Kohn, F. E., Kay, J. H. & Calandra, J. C. (1964b) Subacute oral
toxicity of phosphate starch code No. 4822. Report of Industrial
Biotest Laboratory, Inc., Northbrook, Ill. Submitted to Corn
Products Company, Argo, Ill.
Leegwater, D. C. (1971) Report No. R 3431 by Centraal Instituut voor
Voedingsonderzoek, Zeist, Holland. Submitted to WHO
Pieters, J. J. L., van Staveren, W. A. & Brinkhuis, B. G. A. M. (1971)
Unpublished report No. 3433 by Centraal Instituut voor
Voedingsonderzoek, Zeist, Holland. Submitted to WHO
Roe, F. J. C. (1979) Mineral deposition in the renal pelvis of rats:
A brief review, unpublished report. Submitted to WHO
Til, H. P., Spanjers, M. Th. & de Groot, A. P. (1971) Report No. 3403
of Centraal Instituut voor Voedingsonderzoek, Zeist, Holland.
Submitted to WHO
See Also:
Toxicological Abbreviations
Phosphated distarch phosphate (FAO Nutrition Meetings Report Series 46a)
Phosphated distarch phosphate (WHO Food Additives Series 1)
Phosphated distarch phosphate (WHO Food Additives Series 5)
PHOSPHATED DISTARCH PHOSPHATE (JECFA Evaluation)