ALGINIC ACID AND ITS AMMONIUM, CALCIUM, POTASSIUM AND
SODIUM SALTS
First draft prepared by
Dr G.J.A. Speijers and Mrs M.E. van Apeldoorn
National Institute of Public Health and Environmental Protection
Laboratory for Toxicology
Bilthoven, The Netherlands
1. EXPLANATION
These substances were evaluated at the seventh and seventeenth
meetings of the Committee (Annex 1, references 7 and 32). At the
seventeenth meeting, an ADI of 0-50 mg/kg bw was established. Since
these evaluations, additional data have become available and were
reviewed by the Committee at its present meeting.
Alginate solutions of different viscosities are used as texture
modifiers in a wide variety of food and industrial applications.
2. BIOLOGICAL DATA
2.1 Biochemical aspects
2.1.1 Absorption, distribution and excretion
14C-Labelled alginates were fed as 10% of the diet to
10-week-old rats that had been starved for 24 h; and the subsequent
metabolism over a 17 h period was measured. Eighty-five to
ninety-one % of the radioactivity was recovered in the faeces.
Recoveries of administered 14C in urine (0.11-0.16%), respiratory
CO2 (0.21-0.42%), and plasma (0.002-0.007%), show that alginate
absorption under these conditions of feeding is extremely small
(Humphreys & Triffitt, 1968).
From the clinical experiments reported it appears that alginic
acid does not bind sodium in man to any great extent (Feldman
et al., 1952; Gill & Duncan, 1952).
The absorption of orally administered riboflavin-5'-phosphate
by healthy male subjects was increased significantly when the
vitamin was administered in 50 ml of 2% alginate solution rather
than water alone (Levy & Rao, 1972).
2.2 Toxicological studies
2.2.1 Acute toxicity
Table 1. Acute toxicity of alginic acid and its salts
Compound Animal Route LD50 References
(mg/kg bw)
Alginic acid rat i.p. 1600 Thienes et al.,
1957
Sodium mouse i.v. less than 200 Solandt, 1941
alginate
Sodium mouse i.p. LDLO 500 Arora et al.,
alginate 1968
Sodium rat oral >5000 Woodward
alginate Research Corp.
1972
Sodium rat i.v. 1000 Sokov, 1970
alginate
Sodium rabbit i.v. approx. 100 Solandt, 1941
alginate
Sodium cat i.p. approx. 250 Chenoweth, 1948
alginate
Calcium rat i.v. 64 Sokov, 1970
alginate
Calcium rat i.p. 1407 Sokov, 1970
alginate
Subcutaneous and intramuscular injections of 0.1 ml of a 1%
dispersion of alginic acid were not followed by any injurious
reactions in mice or rats (Chenoweth, 1948).
2.2.2 Short-term studies
2.2.2.1 Rats
Potassium alginate at a level of 5% in the feed acted as a
laxative; calcium alginate 5% was without this effect (Thienes
et al., 1957).
Groups of 4 male and 4 female Charles river CD rats were fed a
control diet or a diet with 10% sodium alginate at the expense of
starch for 12 days. Faecal lipids were increased 5 times in the
alginate group. Total blood cholesterol was decreased but not
significantly. Total faecal sterols were somewhat increased (Mokady,
1973).
When male Sprague-Dawley rats (5-7/group) received for 2 or 4
weeks a non-fibre diet in which 5% sucrose was substituted by 5%
sodium alginate, pancreatic-bile secretion was elevated. When
alginic acid or calcium alginate was fed, no effect on pancreatic
and biliary secretion was observed (Ikegami et al., 1989).
Groups of ten 21-day old male Wistar rats received a diet with
10% casein or 10% soybean proteins with 0, 0.5, 1, 2 or 3% sodium
alginate for 4 weeks. Sodium alginate had no effect on the protein
efficiency ratio (Mouecoucou et al., 1990).
Groups of 5 rats were fed 5%, 10% or 20% of alginic acid in the
diet for two months. Rats on the 20% diet showed a decreased food
consumption and weight gain. Those on lower levels were unaffected
(Thienes et al., 1957).
Groups of 6 rats were fed sodium alginate for 10 weeks at
levels of 5%, 10%, 20% and 30% in the diet. The mortality rate was
high in the 20% and 30% groups during the first two weeks,
apparently due to inanition. Ten per cent or 5% in the diet had no
effect on longevity. The weight gain of the 10% group was slightly
decreased. Five per cent had no effect on weight gain (Nilson &
Wagner, 1951).
Groups of 10 male and 10 female Wistar rats (bw 46.0-47.3 g)
received for 4 or 13 weeks 0, 0, 5, 15 or 45% low viscosity sodium
alginate in their diet. Body weights were recorded weekly. Food
consumption was determined at weeks 1-4 and weeks 12-13. During the
first week faeces were collected. Appearance of faeces was judged at
intervals during 90 days. After 4 weeks one control group and the 5
and 45% groups were discarded. At week 13 haematology (Hb, Ht, Er,
Leu, Diff) in all rats was carried out. In week 14 all rats were
killed, relative organ weights were determined, macroscopy and
microscopy (approximately 25 tissues) in all rats were carried out.
In the first weeks rats on 45% sodium alginate showed abnormal hair
loss resulting in practically complete baldness. Heavy diarrhoea was
seen in the 45% group in the initial phase of the study. In the 15%
group only slightly abnormal faeces were produced during the first
weeks. In the 45% group considerable growth retardation was
observed. At the 15% level growth was normal. In the final 2 weeks
of the study the batch of sodium alginate had to be replaced by
another sample. The feeding of the new material caused a sharp drop
in body weight followed by a recovery which had not yet been
completed at the end of week 12. Low food intake in the 15% group in
the final week of the study is ascribed to the change of the test
batch. The amount of faeces produced per 100 g of food consumed was
considerably increased in rats fed sodium alginate. Haematology did
not show abormalities. A significantly increased weight of the
caecum, both filled and empty, was seen in the 15% sodium alginate
group. Macroscopy showed enlarged, distended, heavy caeca.
Histopathology revealed thickened urothelium with papillomatous
appearance in the urinary bladder of 6/10 male and 3/10 female rats
on 15% sodium alginate. Small calcium deposits under the sometimes
thickened urothelium of the renal pelvis and/or under the surface of
the renal papilla were seen in 6/10 male and 2/10 female rats on 15%
sodium alginate. These changes were not seen in the control group
(Feron et al., 1967).
2.2.2.2 Guinea-pigs
Two groups of five adult male albino guinea-pigs were given 1%
sodium alginate in their drinking water for 10 weeks. A further four
groups of six animals were used for a seven-month study. No ill
effects were observed and no colon ulceration occurred (Watt &
Marcus, 1972).
2.2.2.3 Dogs
Groups of each six beagle dogs (equally divided by sex), were
maintained on diets containing 0, 5 or 15% sodium alginate for one
year. Weight gain, behaviour, appearance, periodic blood values,
terminal urinalysis, blood urea nitrogen, blood glucose and serum
alkaline phosphatase were within normal limits. Gross autopsy and
histopathologic examination of tissues revealed no compound-related
effects (Woodard Research Corp., 1959).
2.2.3 Long-term/carcinogenicity studies
2.2.3.1 Mice
Groups of 75 male and 75 female Swiss mice (age 6 weeks)
received for 89 weeks a control diet or a diet containing sodium
alginate at a dose level gradually increasing to 25% (week 39).
Sodium alginate was incorporated into the control diet at the
expense of equal amounts of the precooked control starch. The mice
were observed daily for condition, behaviour and the appearance of
faeces. Body weights were recorded at weeks 1, 2 and 4 and once
every 4 weeks thereafter. Water intake was measured in at least 5
animals/sex/group in week 87. Haematology was performed in 10
animals/sex/group in weeks 40 and 78. Blood glucose and
urea-nitrogen levels were determined in 10 animals/sex/group in
weeks 78 and 86 after overnight fasting. Urinalysis was conducted in
at least 5 males/group and 8 females/group in weeks 82 and 86,
respectively. In week 87 half of the surviving male and female
animals in the treated group were placed on control diet and 2-5
weeks later urinalysis was performed in 6-8 males. The pH of faeces
was measured in 4-5 males/group in weeks 82 and 85. In week 80, 10
animals/sex/group and in weeks 89-92, all surviving animals were
killed, organ weights were determined and macroscopy and microscopy
were carried out.
In the male control group between weeks 39 and 65, and in the
male alginate group during the last six months, high mortality
occurred due to haemorrhagic myocarditis. This phenomenon is not
uncommon in this strain of mouse. Mean body weights in the alginate
group were decreased from week 8 onwards in males and from week 20
onwards in females. Alginate was nephrotoxic to mice as shown by
extremely high water consumption (5-10 times control value), high
urine production, urinary incontinence (8 males and 2 females), high
pH and low specific gravity of the urine, increased level of blood
urea nitrogen, increased kidney weights, distension of renal calyx
and a high incidence of dilated distal tubules. Furthermore caecal
and colonic enlargement and urinary changes were seen, but these
changes appeared to be reversible and had completely or largely
disappeared within 2-5 weeks after cessation of treatment in week
87. The incidence of intratubular calcinosis or of concretions in
the pelvic space was not reduced during the recovery period. In mice
no renal pelvic calcification accompanied by hyperplasia of the
papillary and pelvic epithelium, as seen in rats fed 15% sodium
alginate in their diet, was observed. Probably the high water
consumption together with the high production of urine with a low
specific gravity prevented formation and deposition of calcareous
concretions in the pelvic space of the kidneys of the mice on 25%
sodium alginate. Furthermore, in mice no hyperplasia of the
epithelium of the urinary bladder, as was seen in rats on 15% sodium
alginate, was observed. No indication for a carcinogenic activity of
sodium alginate in mice was seen (Til et al., 1986).
Infant albino mice (ICR/HA strain) were injected subcutaneously
in the nape of the neck with suspensions of alginic acid (10 and
100 mg/ml) or solvent alone in volumes of 0.1, 0.1, 0.2, and 0.2 ml
on days 1, 7, 14, and 21 respectively after birth (so total dose in
the two test groups was 6 and 60 mg alginic acid, respectively), and
maintained on normal diets for 49 to 53 weeks. The initial number of
mice was 170, 20 and 79, respectively, in the solvent control group,
the 6 mg group and the 60 mg group. Tumour frequency fell within
control ranges. At 21 days 16 out of 20 mice in the 6 mg group and
16 out of 79 mice in the 60 mg group were alive, whereas in the
solvent control group 147 out of 170 animals were alive. At week 49,
10 out of 20 mice in the 6 mg group and only 11 out of 79 mice in
the 60 mg group were alive, whereas in the solvent control group 118
out of 170 animals were alive. Due to the limited number of animals
in the lowest dosage group, the low number of survivors in the
highest dosage group and the short duration of the experiment, the
study is considered to be inappropriate for evaluation of a possible
carcinogenic effect of alginic acid (Epstein et al., 1970).
2.2.3.2 Rats
Two groups of 10 male albino rats were fed two different
commercial preparations of sodium alginate at the 5% level over
their lifespan (maximum 128 weeks). Data on longevity, maximum
weight and food and water consumption indicate no adverse effect.
Gross necropsy studies revealed no abnormalities. Histopathological
examination was not carried out (Nilson & Wagner, 1951).
2.2.4 Reproduction studies
2.2.4.1 Rats
Groups of 40 rats (equally divided by sex) were maintained on
diets containing 0 or 5% sodium alginate for a period of two years.
During this period approximately half the rats were bred once to
produce an F1-generation, which was subsequently bred to produce
an F2-generation. There were no significant differences in growth
rate of test groups and controls, for either the parent group over
the two-year period or the progeny (F1 and F2). Reproductive
performance was normal. Haematological values of the parent group,
as well as those of the F2 offspring, were normal. Gross and
microscopic study of various tissues and organs of the parent groups
at two years, and of the F1 and F2 groups at the conclusion of
the rapid growth period, were normal (Morgan et al., undated).
2.2.5 Special studies on genotoxicity
Table 2. Results of genotoxicity assays on sodium alginate
Test system Test object Dose-levels Results References
used
Ames test Salmonella up to 10 negative1 Isidate et
typhimurium mg/plate al., 1984
Chromosomal Chinese hamster up to 10 negative2 Isidate et
aberrations lung cells mg/ml al., 1984
(CHL cells)
Chromosomal Chinese hamster 1, 50, 100 negative2 Larripa et
aberrations ovary cells µg/per ml al., 1987
Dominant ICr/Ha Swiss i.p. 82, negative3 Epstein et
lethal assay mice 200, 1000 al., 1972
mg/kg bw
1 Assay with metabolic activation.
2 Assay without metabolic activation.
3 Test compound alginic acid.
2.2.6 Special studies on immunotoxicity
2.2.6.1 Mice
Four mice received an injection with 100 µg of sodium alginate
(derived from Mycrocystis pyriforma) 4 days before and at the day
of inoculation with sheep red blood cells. Mice were bled 7 days
after inoculation and serum was assayed for antibodies against sheep
red blood cells by haemagglutination. Sodium alginate caused a
significant increase in haemagglutination titer. However when the
test was repeated the result was negative (Mayer et al., 1987).
2.2.7 Special studies on tumour inhibition
2.2.7.1 Rats
Two groups of 10 male Spague-Dawley rats (age 5 weeks) received
weekly for 12 weeks a s.c. injection with a solution of
dimethylhydrazine (DMH) (dose 20 mg DMH/kg bw adjusted to pH 7 with
sodium bicarbonate). One group received a basal diet while the
second group received 1.5% sodium alginate (crude) in their diet
during the 12 weeks of DMH treatment. The experiment was terminated
8 weeks after the treatment period. Sodium alginate appeared to
exert an inhibitory effect on the development of intestinal tumours
resulting from DMH (Yamamoto & Maruyama, 1985).
2.2.8 Special investigations on the interference of alginate
with minerals
Two groups of 12 male weanling Sprague-Dawley rats received a
control diet or a diet with 10% Na-alginate, at the expense of corn
starch, for 8 days. A marked increase in faecal dry matter was seen
in the alginate group. Ca and Zn absorption were not affected by
alginate. Absorption of Fe, Cr, and Co were significantly reduced in
the alginate group (Harmut-Hoene & Schelenz, 1980).
2.2.8.1 Interference with Cd and Pb
In vitro
Equilibrium dialysis experiments were carried out in solutions
containing varying concentrations of either Cd (as Cd(OH)2) in
saline or Pb (as lead acetate) in water with or without the addition
of 1 g alginic acid/100 ml. Equilibration lasted for a minimum of
24 h at room temperature. The extent of the binding by alginate
increased as metal concentration increased. At concentrations of 10
and 50 µg Pb/L, 0.7 and 5 mg Pb, respectively, was bound per g
alginic acid. At concentrations of 0.01, 0.1, 5 and 10 µg Cd/L 0.09,
0.4, 2.1 and 7.5 mg Cd, respectively, were bound to 1 g alginic acid
(Rose & Quarterman, 1987).
Rats
A group of 6 male rats received for 4 weeks a diet supplemented
with 200 mg Pb/kg (as lead acetate) together with 5 mg Cd/kg (as
cadmium hydroxide). Furthermore, 40 g alginic acid/kg of diet was
added. A control group of 10 male rats received the Pb/Cd
supplemented diet without the addition of alginic acid. Deposition
of Pb and Cd in liver, kidneys and femur was measured. A reduction
of growth was seen in the alginic acid group. Alginic acid had no
effect upon Cd deposition, but Pb content in femur and kidneys was
doubled.
Five groups of 6 male rats received 0, 1, 5, 10 or 40 g alginic
acid in their diet for 4 days. On the third day all rats received by
stomach tube 0.2 ml saline containing 2 µg radioactive Pb. On day 4
the rats were killed and radioactivity in blood, duodenal mucosa,
liver, kidney and gut-free carcass was measured. Pb retention was
already increased at 1 g alginic acid/kg of diet (Rose & Quarterman,
1987).
Humans
In a limited trial with 3 human volunteers, the absorption of
203Pb was unchanged by alginate supplement (Harrison et al.,
1969).
2.2.8.2 Interference with radium
Mice
Male mice (C57 Black, age 3 months) given a single i.p.
injection with 226RaCl2 and fed from day 3 thereafter with bread
containing 10% sodium alginate (intake Na-alginate was 13 g/kg bw)
showed a reduction of the 226Ra content in the femur without
decalcification. The amount of 226Ra decorporated was independent
of the dose of 226Ra injected i.p. 226Ra content of blood was
doubled and 226Ra content of faeces showed a 60% increase. Urinary
level of 226Ra was not changed significantly (Kestens et al.,
1980).
Mice (BALB/c, age 3 months), given bread with 6% sodium
alginate 2 h before oral administration (by gavage) of 226RaCl2,
revealed a more than 100 times reduction of Ra uptake (measured in
whole body). In the same experiment 47Ca uptake was only 1.2 times
less than in controls (Vanderborght et al., 1971).
2.2.8.3 Interference with strontium
Humans and animals
Several experiments in humans and animals which demonstrated a
reduction of Sr uptake when Sr isotopes were administered very early
before or together with alginate, in the majority of the cases via
the oral route. In animals reductions of Sr intake of 1.2 to 10-fold
were measured. The radioactive Sr isotopes were determined in
carcass, skeleton, femur or whole body. In humans reductions in Sr
uptake of 1.6 to 24--fold were reported. Radioactive Sr isotopes
were measured in whole body or plasma (Vanderborght et al. 1971).
Mice
Male C57 Black mice (which had been contaminated with 85Sr
3 weeks previously) were fed a dough containing 5% sodium alginate
showed an increased 85Sr content of the blood (Vanderborght
et al., 1971). It was hypothesized that the increased 85Sr
content in blood was due to a shift in Sr-equilibria between
intestinal lumen, blood and the skeleton (Van Barneveld et al.,
1977).
Simultaneous i.p. and oral (via a diet with starch containing
dough) treatment of male Black mice with sodium alginate which had
been contaminated with 85Sr 9 weeks previously, resulted in a
5-fold increase of the blood content of 85Sr. 85Sr content of
liver, kidney and spleen is increased 4-6 times by this combined
treatment. Urinary and faecal excretion of 85Sr were increased 1.2
and 1.8 times, respectively. Treatment with dietary alginate only
caused a 2.5-fold rise in blood 85Sr content, 1.5-2 times
increases of 85Sr contents in liver, spleen and kidney, a 2.1
times rise in faecal excretion of 85Sr and urinary excretion was
somewhat lowered. I.p. treatment with alginate only resulted in a
2.3-fold increase in blood 85Sr content, 2.3-3.6-fold increases of
85Sr contents of liver, spleen and kidney and a 1.7-fold increase
in urinary 85Sr excretion, while faecal excretion was not changed.
The biological half-life of Sr is about halved by the treatment with
alginate via the diet together with i.p. alginate injection.
Treatment with alginate via the diet only will speed decorporation
of Sr from skeleton by about 40% (Vanderborght et al., 1978).
2.2.8.4 Interference with calcium
Rats
Rats received diets supplemented with calcium and phosphate
with and without 10% sodium alginate. No effect on the absorption
and skeletal retention of calcium was observed (Slat
et al., 1971).
Humans
Calcium balance experiments on six healthy adults taking 8 g of
sodium alginate daily for seven days failed to show any interference
with the absorption of calcium from a normal mixed diet (Millis &
Reed, 1947).
In 14 out of 15 men receiving 1.5 g sodium alginate the
gastrointestinal content of strontium was reduced by a factor of two
while calcium absorption was hardly affected (Harrison et al.,
1966).
The absorption and retention of 47Ca and 85Sr was compared
for four human volunteers on a normal diet with and without sodium
alginate supplement. Fifteen to twenty grams alginate/day was given
for seven days. Alginate decreased the retention of 85Sr and
47Ca by about 70 and 7%, respectively. No changes in excretion
pattern of Na, K, Mg or P were observed (Carr et al., 1968).
2.2.8.5 Interference with barium
Rats
Rats were fed diets with 10% alginate (3 different types). At
day 3 or 4 on diet the animals received an oral, i.p. or s.c. dose
of 133Ba. The retention of barium in the carcass after oral
administration was reduced 4 to 8 times with the different types of
alginate. Four days after parenteral administration of radiolabelled
barium, the barium content of the carcass was 5-12% lower than in
controls accompanied by a small increase in faecal excretion of the
marker (Sutton et al., 1972).
2.2.9 Observations in humans
Six healthy adults were given 8 g of sodium alginate daily for
seven days without untoward effects (Millis & Reed, 1947).
Three patients whose clinical condition warranted sodium
restriction were given oral doses of 15 g of alginic acid three
times daily for seven days. A slightly increased faecal sodium and
potassium excretion was noted, but no changes in plasma electrolyte
concentration (Feldman et al., 1952).
Six patients with essential hypertension were given daily doses
of 45 g of alginic acid containing 10% of potassium alginate for
five to nine weeks and three patients in an oedematous state were
given the same dosage for about a week. It was well tolerated and
produced no gastrointestinal disturbance (Gill & Duncan, 1952).
Five healthy male volunteers received 175 mg sodium alginate/kg
bw/day for 7 days, followed by 200 mg/kg bw for a further 16 days.
The daily doses were consumed in three measured portions at
intervals each day. The portions were prepared by adding the weighed
aliquots of sodium alginate by rapid stirring to 220 ml cold
distilled water. The hydrocolloid was then allowed to hydrate for
24 h to a thick, but fluid gel to which each volunteer added a
predetermined amount of orange juice prior to consumption. The
treatment period was preceded by a 7 day initial control period
during which a daily amount of orange juice, equal to that to be
taken later, was consumed. During the treatment period enquiries
were made with respect to apparent allergic responses. At day 3 of
the initial control period, on the last day of the 23 day treatment
period and on the last day of the 7 day recovery period the
following parameters were examined; fasting blood glucose, plasma
insulin, breath hydrogen concentrations, haematological parameters
(Hb, Ht, MCV, MCH, MCHC, Er, Leu, Diff, platelets) and biochemical
parameters (Na, Cl, K, CO2, urea, LDH, AST, bilirubin, alk.
phosphatase, phosphate, Ca, protein, albumin, creatinine, urate,
lipids, cholesterol, HDL cholesterol and triglycerides). Routine
urinalysis was carried out during the initial control week and
during the third week of treatment. Five day faecal collections were
made during days 2-6 of the initial control period and during days
16-20 of the treatment period. Faecal transit time, wet weight, dry
weight, water content, pH, occult blood, neutral sterols, fat,
volatile fatty acids and bile acids in faeces were determined. No
allergic reactions were reported nor observed. Sodium alginate acted
as a bulking agent of moderate efficiency as indicated by a
significant increase in faecal dry and wet weight and an increase in
water content of faeces without a significant change in transit
time. Faecal pH remained normal. Total faecal volatile acids
increased in four volunteers but decreased in one. No changes in
faecal total and individual neutral sterols or in total and
individual bile acids were seen. Haematological, biochemical and
urinalysis parameters did not show significant changes with the
exception of some parameters of one volunteer who suffered from
influenza (Anderson et al., 1991).
Two-hundred-and-eight workers who are exposed to dust from
dried milled seaweed and pure alginate compounds in an alginate
factory were examined for pulmonary hypersensitivity. Fifteen out of
these 208 workers showed symptoms definitely related to dust
exposure at work. Serological tests showed that 8 of the 15 workers
with definite symptoms and one worker without definite symptoms had
precipitating antibodies to prepared extracts in their serum.
Chest X-rays of these 16 workers were normal. Twelve workers
with either evidence of work related respiratory symptoms or
precipitating antibodies in their serum or both (3 out of 12) were
exposed to an atmosphere artificially contaminated with raw seaweed
dust for a maximum of one hour. Measurements of pulmonary function
were made before, immediately after, and 1, 3, 5 and 24 h after
exposure. A significant reversible deterioration in pulmonary
function was seen as shown by an acute and sometimes severe airway
obstruction, followed by a delayed loss of lung volume with
reduction in transfer factor (Henderson et al., 1984).
3. COMMENTS
Three limited long-term dietary studies, one in mice and two in
rats, provided no indication of a carcinogenic effect of alginates.
Neiher an in vitro nor an in vivo genotoxicity study showed any
genotoxic activity. No effects on the reproduction of rats were
observed, but the experimental design of the study was limited. A
long-term study in mice using only a single dose level of 25% sodium
alginate in the diet showed a clear effect (soft stool, distended
caecum, decreased growth and deposition of calcium in the pelvis of
the kidney).
In a 90-day study in rats, 15% sodium alginate in the diet
resulted in an enlarged, distended, heavy caecum, a papillomatous
appearance in the urinary bladder and calcium deposits in the renal
pelvis and/or renal papilla. A slight decrease in growth was seen in
only one short-term experiment with rats at the 10% level, but the
effects were not specific and were also seen with other poorly
absorbed compounds. Recent studies have shown slight interference
with the absorption of a number of minerals.
4. EVALUATION
The Committee recalled the similar effects of poorly absorbed
compounds (modified celluloses, polyalcohols, gums, modified
starches) reviewed in Section 2.2.3 of the report of the
thirty-fifth meeting (Annex 1, reference 88); for such compounds an
ADI "not specified" usually had been allocated. The Committee
therefore allocated a group ADI "not specified" to alginic acid and
its ammonium, calcium, potassium and sodium salts, but pointed out
(as it had for other compounds causing this effect) that laxative
effects might occur at a high level of intake.
Propyleneglycol alginate was evaluated at the Committee's
seventeenth meeting (Annex 1, reference 32) when an ADI of
0-25 mg/kg bw was allocated. It was not re-evaluaed at the present
meeting.
5. REFERENCES
ANDERSON, D.M., BRYDON, W.G., EASTWOOD, M.A. & SEDGWICK, D.M. (1991)
Dietary effects of sodium alginate in humans. Food Add. Contam.,
8: 237-248.
ARORA, C.K., CHAUDHURRY, S.K. & CHAUHAN, P.S. (1968) Sodium-alginate
toxicity in mice. Indian J. Physiol. Pharmacol., 12: 129-130.
CARR, T.E.F., HARRISON, G., HUMPHREYS, E. & SUTTON, A. (1968)
Reduction in the absorption and retention of dietary strontium in
man by alginate. Int. J. Radiol. Biol., 14: 225.
CHENOWETH, M.B. (1948) Toxicity of sodium alginate in rats. Ann.
Surg., 127: 1173.
EPSTEIN, S.S., FUJII, K., ANDREA, J. & MANTEL, N. (1970)
Carcinogenicity testing of selected food additives by parenteral.
Tox. Appl. Pharmacol., 16: 321-334.
EPSTEIN, S.S, ARNOLD, E., ANDREA, J., BASS, W. & BISHOP, Y. (1972)
Detection of chemical mutagens by the dominant lethal assay in the
mouse. Tox. Appl. Pharmacol., 23: 288-325.
FELDMAN, H.S., URBACH, K., NAEGELE, C.F., REGAN, F.D. & DOERNER,
A.A. (1952) Cation adsorption by alginic acid in humans. Proc. Soc.
Exp. Biol. Med., 79: 439-441.
FERON, V.J., TIL, H.P. & GROOT, A.P. DE (1967) Unpublished Report of
the Central Institute for Nutrition and Food Research TNO, Zeist,
The Netherlands to Kon. Scholten-Honig N.V. (Foxhol) and
AVEBE-D.W.M. (Veendam). Report R2456. Sub-chronic toxicity test with
a modified potato starch (propylene oxide) and an alginate in albino
rats. July 1967.
GILL, R.J. & DUNCAN, G.G. (1952) The clinical use of alginic acid as
a cation exchanger. Amer. J. Med. Sci., 224: 569-472.
HARMUT-HOENE, A. & SCHELENZ, R. (1980) Effect of dietary fiber on
mineral absorption in growing rats. J. Nutr., 110: 1774-1784.
HARRISON, G.E., McNEILL, K.G. & JANICA, J. (1966) The effect of
sodium alginate on the absorption of strontium and calcium in human
subjects. Can. Med. Ass. J., 3: 532-534.
HARRISON G.E., CARR, T.E.F., SUTTON, A. & HUMPHREYS, E.R. (1969)
Effect of alginate on the absorption of lead in man. Nature, 224:
1115-1116.
HENDERSON, A.K., RANGER, A.F., LLOYD, J., McSHARRY, C., MILLS, R.J.
& MORAN, F. (1984) Pulmonary hypersensitivity in the alginate
industry. Scott Med. J., 29: 90-95.
HUMPHREYS, E.R. & TRIFFITT, J.T. (1968) Absorption by the rat of
alginate labelled with Carbon-14. Nature, 219: 1172.
IKEGAMI, S., TSUCHIHASHI, F., HARADA, H., TSUCHIHASHI, N., NISHIDE,
E. & INNAMI, S. (1989) Effect of viscous indigestible
polysaccharides on pancreatic-biliary secretion and digestive organs
in rats. J. Nutr., 120: 353-360.
ISHIDATE, M., JR., SOFUNI, T., YOSHIKAWA, K., HAYASHI, M., NOHMI,
T., SAWADA, M. & MATSUOKA, A. (1984) Primary mutagenicity screening
of food additives currently used in Japan. Food Chem. Toxicol., 22:
623-636.
KESTENS, L., SCHOETERS, G., VAN PUYMBROECK, S. & VANDERBORGHT, O.
(1980) Alginate treatment and decrease of 226Ra retention in the
mouse femur after an i.p. contamination with various radium doses.
Health. Phys., 39: 805-809.
LARRIPA, I.B., MUDRY DE PARGAMENT, M., LABEL DE VINUESA, M. & MAYER,
M.S. (1987) Biological activity in Macrocystis pyrifera from
Argentina: sodium alginate, fucoidan and laminaran. II.
Genotoxicity. Hydrobiologia, 151/152: 491-496.
LEVY, G. & RAO, K. (1972) Enhanced intestinal absorption of
riboflavin from sodium alginate solution in man. J. Pharm. Sci.,
61: 279-280.
MARTIN, G. (1986) Evaluation toxicologique et nutritionelle des
alginates. I. Définition, structure, fabrication, propriétés et
applications. Sciences et Aliments, 6: 473-486.
MAYER, A.M.S., KROTZ, L., BONFIL, R.D., BUSTUOBAD, O.D., GROISMAN,
J.F., DE LEDERKREMER, R.M. & STIERLE, D.B. (1987) Biological
activity in Macrocystis pyrifera from Argentina: sodium alginate,
fucoidan and laminaran. I. Antitumor, cytotoxicity and humoral
immune response. Hydrobiologia, 151/152: 483-489.
MILLIS, J. & REED, F.B. (1947) The effect of sodium alginate on the
absorption of calcium. Biochem. J., 41: 273-275.
MOKADY, S. (1973) Effect of dietary pectin and algin on blood
cholesterol level in growing rats fed a cholesterol-free diet.
Nutr. Metabol., 15: 290-294.
MORGAN, C.F., FABER, J.E., Jr. & DARDIN, V.J. (undated) Unpublished
report from Georgetown University Medical School, Washington, D.C.
MOUECOUCOU, J., VILLAUME, C., BAU, H.M. BAU, NICOLAS, J.P & MEJEAN,
L. (1990) Effets des alginates et des carraghenates de sodium
associés aux protéines de soja sur le coéfficient d'efficacité
protéique (CEP). Reprod. Nutr. Dev., 30, 541-547.
NILSON, H.W. & WAGNER, J.A. (1951) Feeding tests with some algin
products. Proc. Soc. Exp. Biol. Med., 76: 630-635.
ROSE, H.E. & QUARTERMAN, J. (1987) Dietary fibers and heavy metal
retention in the rat. Environ. Res., 42: 166-175.
SLAT, B., KOSTIAL, K. & HARRISON, G.E. (1971) Reduction in the
absorption and retention of strontium in rats. Health Phys., 21,
811-814.
SOLANDT, O.M. (1941) Some observations upon sodium alginate. Quart.
J. Exp. Physiol., 31: 25.
SOKOV, L.A., (1970) Radioaktivnye Izotopy Vo Vneshnei Srede i
Organizine. Atomizidat, Moscow 247.
SUTTON, A., HUMPHREYS, E.R., SHEPHERD, H. & HOWELLS, G.R. (1972)
Reduction in the retention of radioactive barium in rats following
the addition of sodium alginate derivatives to the diet. Int. J.
Radiat. Biol., 22, 297-300.
THIENES, C.H., SKILLEN, R.G., MEREDITH, O.M., FAIRCHILD, M.D.,
McCANDLESS, R.S. & THIENES, R.P. (1957) The hemostatic laxative and
toxic effects of alginic acid preparations. Arch. int.
Pharmacodyn., 111: 167-181.
TIL, H.P., FERON, V.J. & IMMEL, H.R. (1986) Chronic (89-week)
feeding study with hydroxypropyl distarch phosphate, starch acetate,
lactose and sodium alginate in mice. Food Chem. Toxicol., 24:
825-834.
VAN BARNEVELD, A.A., VAN PUYMBROECK, S. & VANDERBORGHT, O. (1977)
The action of sodium alginate in the food on a 85Sr body-burden in
mice. Health Phys., 33: 533-537.
VANDERBORGHT, O., VAN PUYMBROECK, S. & COLARD, J. (1971) Intestinal
absorption and body retention of 226-radium and 47-calcium in mice:
effect of sodium alginate, measured in vivo with a Ge(Li)
detector. Health Phys., 21, 181-196.
VANDERBORGHT, O.L.J., VAN PUYMBROECK, S. & BABAKOVA, I. (1978)
Effect of combined alginate treatments on the distribution and
excretion of an old radiostrontium contamination. Health Phys. 35:
255-258.
WATT, J. & MARCUS, R. (1971) Effect of degraded and undegraded
alginates on the colon of guinea-pigs. Proc. Nutr. Soc., 30: 81A.
WOODARD RESEARCH CORP. (1959) Unpublished report submitted to Kelco
Co.
WOODARD RESEARCH CORP. (1972) Unpublished report submitted to Kelco
Co.
YAMAMOTO, I. & MARUYAMA, H. (1985) Effect of dietary seaweed
preparations on 1,2-dimethylhydrazine-induced intestinal
carcinogenesis in rats. Cancer Letters, 26: 241-251.
See Also:
Toxicological Abbreviations
Alginic acid and its ammonium, calcium, potassium and sodium salts (WHO Food Additives Series 5)