ACETYLATED DISTARCH PHOSPHATE
Explanation
This substance was evaluated for acceptable daily intake for man
(ADI) by the Joint FAO/WHO Expert Committee on Food Additives in 1969
and 1971 (see Annex I, Refs. 20 and 27). A toxicological monograph was
issued in 1974 (see Annex I, Ref. 33).
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
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.
BIOLOGICAL DATA
BIOCHEMICAL ASPECTS
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).
TOXICOLOGICAL STUDIES
Special studies on kidney lesions associated with dietary modified
starches
Rat
Groups of 25 female Sprague-Dawley rats were fed diets containing
either 30% acetylated distarch phosphate or 30% unmodified starch
(control) in a 1-year study with weanling rats (Experiment I) and a
separate 9-month study utilizing 9-month-old rats (Experiment II). The
Ca concentration in the diet was c. 1%, P concentration c. 0.8% and Mg
c. 0.15%. Urinary calcium concentration and total daily output were
significantly increased in animals on the test diet (Experiments I and
II), but only minor differences occurred in phosphorus, oxalate,
magnesium and creatinine excretion. No significant effects were
observed on body weight, food consumption, urine volume, urine pH and
crystal content or faecal mineral content in animals on the test diet.
At autopsy, caecal enlargement was present in treated animals, but no
other treatment-related effects on relative organ weights were
observed. No treatment-related histopathological effects were observed
in the uterus or lower urinary tract, liver, parathyroid, caecum or
ovaries in either experiment. Histological examination of kidney
sections demonstrated the presence of treatment-related pelvic
nephrocalcinosis. An apparent correlation was observed between the
increased incidence of pelvic nephrocalcinosis, increased accumulation
of calcium in the kidney, and increased urinary excretion of calcium.
Residues of calcium in kidney tissue were significantly higher in test
groups than in control (Hodgkinson et al., 1981).
Roe (1979) has conducted an extensive review 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).
Special studies on reproduction
Rat
A 3-generation study was performed using groups of 10 males and
20 females of the P, F1 and F2 generations to produce 2 successive
litters in each generation by mating at weeks 12 and 20 after weaning.
Ten males and 10 females of the F1b generation were kept for 3 weeks
after weaning and then sacrificed for histopathological studies. The
P, F1b and F2b 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% vinyl acetate
and 1.2% phosphorus oxychloride (D.S. of 0.064, 0.043% phosphorus
introduced). No adverse effects were noted with respect to health,
behaviour, mortality, growth, fertility, litter size, resorption
quotient, weaning weight or mortality of young. Caecal weight of
parent rats fed the modified starches was not increased. Gross
pathology revealed a slightly decreased thyroid weight and a slightly
increased caecum weight in F3a rats fed the starch treated with
acetic anhydride and phosphorus oxychloride. Histopathology failed to
reveal any treatment-related changes (De Groot et al., 1974).
Weanling Wistar-derived rats were segregated by sex into groups
of 10 males and 20 females and fed a test diet consisting of 10%
acetylated distarch phosphate + 20% unmodified starch and a control
diet of 30% unmodified starch throughout the pre-mating, gestation and
lactation periods. Control animals received equivalent levels of
unmodified starch in their diet. At weeks 12 and 20, all rats were
mated in groups of 5 males and 10 females to produce 2 successive
litters (F1a and F1b). Litters were randomly culled on day 1 to 8
pups when required. Ten male and 20 female weanlings were randomly
selected from the F1b litter and the above procedure repeated to
produce F2a and F2b litters. In similar fashion, male and female
weanlings from the F2b generation were mated to produce F3a and F3b
litters. After weaning their second litter, dams were sacrificed and
the uterus examined for implantation sites. Ten male and 20 female
weanlings were selected from the F3b litters and continued on their
diets for 3 more weeks before sacrifice. No treatment-related
differences in mortality or fertility were observed between the test
groups and controls. The growth rate of the pups in all groups given
acetylated distarch phosphate was comparable with that in the
controls, and mortality in utero (resorption quotient) and preweaning
mortality were low in all groups. The rats from the F3b generation,
sacrificed 3-4 weeks after weaning, showed no treatment-related gross
or histological changes (de Groot et al., 1974).
Special studies
Groups of 10 male and 10 female rats were fed 0, 25 or 50% of 2
different modified starches (acetic anhydride and vinyl acetate
modified) in a low residue diet for 7 days followed by the additional
feeding of 4% cellulose for 3 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 & Spanjers, 1970).
Short-term studies
Hamster
Groups of 10 male and 10 female Syrian Golden hamsters, weighing
30-40 g, were fed a diet containing either 30% acetylated distarch
phosphate or 30% untreated starch for 30 days. Hamsters fed the test
diet exhibited a reduction in average daily weight gain, compared to
control animals, but the average daily test diet intake was also
reduced. Comparison of feed consumption to corresponding weight gain
did not indicate a significant difference in efficiency of utilization
of the test and control diets. No treatment-related differences were
noted in haematology, clinical chemistry or urinalysis data. No
treatment-related lesions were evident in histological sections from
liver and kidney (Newberne & Buttolph, 1977).
Rat
Groups of 10 male and 10 female rats were fed 0, 25 and 50% of 2
different modified starches (acetic anhydride and vinyl acetate
modified) in their diet for 8 weeks. Body weights of animals on the
higher test levels were somewhat lower than at the 25% levels 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 abnormalities of the enlarged caeca were
noted (de Groot & Spanjers, 1970).
Pig
Groups of 4 male and 4 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 2 or in any other animal (Shillam et al., 1971).
A further pig study in which groups of 8 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).
Long-term studies
Rat
Groups of 30 male and 30 female rats were fed 2 different
modified starches (acetic anhydride and vinyl acetate 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 with either modified starch.
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).
Groups of 30 male and 30 female weanling Wistar-derived rats were
fed diets containing 0, 5, 10 and 30% acetylated distarch phosphate
and 30% unmodified starch (control) for 2 years. A slight growth
retardation was observed at the 30% dietary level, with an increase in
the relative weight of the caecum. The caecal enlargement was
attributed to an adaptive response to the presence of indigestible
material, rather than to a pathological response. Females exhibited an
apparent dose-related increase in relative adrenal weight. Other
organs exhibited slightly increased weight at higher dose levels, but
these findings were, in most cases, considered incidental because
histological sections revealed no treatment-related effects. The only
treatment-related effect that was observed histologically was a kidney
lesion which occurred at a higher incidence in the high dose males.
The lesion consisted of focal hyperplasia of the renal papillary and
pelvic epithelium accompanied by calcified patches in the underlying
tissues. No treatment-related effect was observed on the pattern of
neoplasm development, or on food intake, survival, haematology or
clinical chemistry (de Groot et al., 1974).
OBSERVATIONS IN MAN
Twelve volunteers consumed on each of 4 successive days, 60 g
acetylated distarch phosphates of either 1.5% 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 noted (Pieters et al., 1971).
Comments
The feeding studies with rats show that the modified starch is
well utilized. The available evidence for the group of modified
starches considered suggests that caecal enlargement without
associated histopathological changes is without toxicological
significance. The short-term study shows no other significant effects
related to treatment, the observed growth depression being the obvious
result of the high dietary level used. A reproduction study in rats
showed no significant compound-related effects. A long-term feeding
study in rats showed no compound-related effect, apart from decreased
weight gain, caecal enlargement, and an increased incidence of renal
epithelial hyperplasia in female rats. Data derived from special
studies with a group of modified starches suggest that the latter
effect is due to an imbalance in dietary Ca/F and Mg.
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.
REFERENCES
De Groot, A. P. & Spanjers, M. Th. (1970) Unpublished 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, 651-663
Hodgkinson, A., Robertson, W. G., Fourman, J. & Davis, D. (1981) A
comparison of the effects on mineral metabolism of diets
containing waxy maize starch, either of two chemically-modified
waxy maize starches, or lactose. Unpublished report from the
General Infirmary, and from the Medical School, University of
Leeds (1981). Submitted by the US Food and Drug Administration to
the World Health Organization, 1982
Leegwater, D. C. (1971) Unpublished report No. F 3431 by Centraal
Instituut voor Voedingsonderzoek, Zeist, Holland
Newberne, P. M. & Buttolph, M. L. (1977) A preliminary report of a
thirty-day study in hamsters fed modified starches. Unpublished
report from Massachusetts Institute of Technology (1977),
submitted by the US Food and Drug Administration to the World
Health Organization, 1982
Pieters, J. J. L., van Staveren, W. A. & Brinkhuis, B. G. A. M. (1971)
Unpublished report No. R 3433 by Central Instituut voor
Voedingsonderzoek, Zeist, Holland
Roe, F. J. C. (1979) Mineral deposition in the renal pelvis of rats: A
brief review. Unpublished report submitted to the World Health
Organization
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., Feron, V. J., Spanjers, M. Th. & de Groot, A. P. (1971a)
Chronic (two-year) feeding study in rats with two chemically
modified starches (acetylated distarch phosphate and acetylated
diamylopectin phosphate). Unpublished report from report No. R
3351. Centraal Instituut voor Voedingsonderzoek, Zeist, Holland.
Submitted to WHO
de Groot, A. O., Til, H. P., Feron, V. J., Dreef-van der Meulen, H. C.
& Willems, M. I. (1971b) Two-year feeding and multigeneration
studies in rats on five chemically modified starches. Unpublished
report from Centraal Instituut voor Voedingsonderzoek, Zeist,
Holland. Submitted to WHO
See Also:
Toxicological Abbreviations
Acetylated distarch phosphate (FAO Nutrition Meetings Report Series 46a)
Acetylated distarch phosphate (WHO Food Additives Series 1)
Acetylated distarch phosphate (WHO Food Additives Series 5)
ACETYLATED DISTARCH PHOSPHATE (JECFA Evaluation)