KARAYA GUM (STERCULA)
EXPLANATION
This substance has been evaluated for acceptable daily intake
by the Joint FAO/WHO Expert Committee on Food Additives in 1969,
1973, 1977, 1980, 1983, 1986 and 1987 (Annex 1, references 19, 32,
44, 50, 62, 70 and 73). Toxicological monographs were issued in
1969, 1973 and 1983 (Annex 1, references 20, 33 and 63). A temporary
ADI of 0-20 mg/kg bw was established in 1983 and the Committee
required submission of the results of a short term feeding study in
a non-rodent species by 1985. The 1985 Committee extended the
temporary ADI of 0-20 mg/kg bw and requested submission of more
detailed information on the submitted feeding study by 1986. At the
1986 meeting another report of the study was submitted to the
Committee for review, but it still lacked the detailed information
needed for a proper evaluation. However, the Committee was informed
that a feeding study in monkeys was in progress. The Committee
therefore agreed to extend the existing temporary ADI of 0-20 mg/kg
bw and requested the submission of detailed information by 1988.
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.
BIOLOGICAL DATA
Biochemical studies
Absorption and metabolism
Karaya gum does not disintegrate or decompose appreciably in
the alimentary tract. In a study of 10 dogs, 95% of the orally
administered gum was recovered in the faeces. It absorbs a large
quantity of water and therefore acts as a mechanical laxative. It
tends to increase faecal nitrogen excretion, does not affect starch
digestion in the dogs and does not inhibit the utilization of
vitamin A in rats (Ivy & Isaacs, 1938).
The caloric value was determined in groups of 10 rats fed for
one week 5 g basal diet with either 1 g and 3 g corn starch or 1 g
and 3 g karaya gum supplements. At the 1 g level, karaya gum only
had 30% of the caloric value of corn starch. At the 2 g level
growth was depressed. The intestine was enlarged in all rats on gum
(Wisconsin Alumni Research Foundation, 1964).
The action of 10 species of Bacteroides found in the human
colon on dietary fibre has been studied. Karaya gum is not utilized
by these bacteria and remains unchanged (Salyers, 1977).
Fermentations of 10 polysaccharides by species of the family
of Enterobacteriaceae were examined. Karaya gum was not fermented
by any of the strains tested. As food additive, karaya gum seems
safe from destruction by facultative fermenters (Ochuba & von
Riesen, 1980).
Two groups of four male rats (365-459 g) were fed pelleted
diet containing 5% (w/w) karaya gum over a 24-hour period. Urine
and faeces from each animal were collected and weighed after 24, 48
and 72 hours Faeces were examined, after methanolysis, by GC-MS and
the quality and monosaccharide composition of the faecal
polysaccharides were compared with the dose and original
composition of the gum polysaccharides. It was estimated that 95%
of the gum consumed was recovered as faecal polysaccharide.
Rhamnose was not detected in the urine. The absence of this
component demonstrates that it is not liberated from karaya gum
during its transit through the intestine. These findings indicate
that extensive degradation involving chains and chain terminations
did not occur. The study has not produced any evidence suggesting
metabolic modification of karaya gum in the intestinal tract of the
rat when the gum is added to a normal rat diet (Brown et al.,
1982).
A finely powdered (passing 150 mesh) gum karaya (GK) was added
to the basic diet (Spratts' No. 1 powder) at the 7% (w/w) level.
This dose level was selected so as to exceed, slightly, the
no-effect level established from 90-day dietary studies, e.g. 5%. This
supplemented diet was ingested by a group (unspecified number) of
Albino Wistar rats for 45 days, during which time their initial body
weights, range 99-120 g, increased an average by 233 g (controls) and
229 g (GK). The study indicates that the ingestion of GK for 45 days
does not cause abnormalities in the organelles within the cells of rat
jejunum, ileum and caecum. Neither inclusions nor other ultra-
structural or pathological differences between the control animals
and experimental animals fed diets supplemented with karaya gum
were detected (Anderson et al., 1986).
Toxicological Studies
Special studies on teratogenicity
The administration of up to 170 mg/kg bw of the test material
to pregnant mice for 10 consecutive days had no clearly discernable
effect on nidation nor on maternal or foetal survival. The number
of abnormalities seen in either soft or skeletal tissues of the
test groups did not differ from the number occurring spontaneously
in the controls. In a concurrent group of mice dosed at a level of
800 mg/kg bw, a significant number of maternal deaths (9 out of 28)
occurred. The surviving dams appeared to be completely normal and
bore normal foetuses with no effect on the rate of nidation or
survival of live pups in utero. It was concluded that the test
material was not a teratogen in mice (US FDA, 1972; US FDA, 1973).
In further studies 1% and 10% aqueous suspensions were given
orally and a 1% suspension was given intraperitoneally to pregnant
mice in the 11th to 15th days of gestation. In these tests, GK had
no influence on fetal development (Frohberg et al., 1969).
Special studies on immunoresponse
Female CBA mice, 6 to 8 per group, aged 6 weeks, were used.
They were immunized by injection of 0.1 mg gum in a volume of
0.05 ml, in complete Freund's adjuvant, into the left hind footpad.
Twenty one days after primary immunization, the presence of
delayed-type hypersensitivity was measured by a skin test. Gum
karaya (0.1 mg) dissolved in 0.15 M saline in a volume of 0.05 ml
was injected intradermally into the plantar side of the right
footpad. Footpad thickness was measured in triplicate immediately
before the intradermal injection, and 24h later. Gum karaya is
capable of eliciting an immune response which is comparable to the
specific immune responses elicited by a protein antigen, hen's egg
ovalbumin (Strobel et al., 1982).
Two preparations of gum karaya (Sterculia spp.) have been used
to investigate the immunogenicity and specific irritant properties
of the gum. Sample KA was completely characterized chemically and
conforms to the current EEC (E416) and JECFA specifications. Sample
B, a white powder of Sudanese origin (Sterculia setigera) also
conformed to the above specifications. The animals used were groups
of six to eight mice (C57BL/6J × DBA/2)F1 (BDF1). The time course
of the experiments was as follows: day 0 immunization with 0.2 mg gum
or saline in complete Freund's adjuvant, intradermally into one hind
footpad; day 21 skin test with 0.1 mg antigen into the other
footpad; day 22 measure footpad swelling; day 28 bleed out under
general anesthesia and measure antibody levels. Serum antibody
levels were measured by an ELISA technique and delayed hyper-
sensitivity responses by a footpad swelling test. Antigenic
cross-reactivity within each gum species was tested in a crossover
fashion. All gum preparations elicited systemic immune responses
after immunization. Further processing reduced immunogenicity,
although there was no evidence that systemic immunity to these
complex polysaccharide antigens responses could be completely
abolished by processing or purification. The ethanolic extract of
gum karaya caused considerable footpad swelling when injected
intradermally (Strobel et al., 1986).
Special studies on mutagenicity
The host-mediated assay of karaya gum did not produce any
measurable mutagenic response or alteration in the recombination
frequency of Saccharomyces cerevisiae in either host-mediated
assay or the associated in vitro tests. The cytogenetic assay of
karaya gum exhibited no adverse effect on either metaphase
chromosomes from rat bone marrow or anaphase chromosomes from in
vitro culture of human embryonic lung cells at any of the dose
levels or time periods tested. No consistent responses were
reported in the dominant lethal test to suggest that karaya gum is
mutagenic to the rat as a result of this experimental procedure
(Newell & Maxwell, 1972, available in summary only).
Acute toxicity
The acute oral LD50 of 12 food-grade gums (sodium and calcium
carragheenate, tragacanth, ghatti, locust bean, arabic, guar,
karaya, propylene glycol, alginate, furcellaran, agar-agar and Na
carboxymethylcellulose) was studied. Each material was administered
by gavage to five groups of 10 rats, with five males and five
females in each group. Vehicles utilized were water, mineral oil,
corn oil and soybean oil. The animals were fasted 18 hours prior to
dosing with food and water available ad libitum during the 24-day
observation period. LD50 values observed ranged from 2.6 to
18.0 g/kg with most values in the 5-10 g/kg range. The rabbit was
reported to be the most sensitive species and the rat and mouse the
least sensitive (Bailey et al., 1976, available in summary only).
Short-term studies
Mice
Groups each of 16 mice, equally divided by sex were fed
diets containing 0, 2, 10, 20 or 40% Gum Karaya, for 3 weeks.
Histological examination of all important organs showed no compound
related effect. In another study groups of 20 weanling mice were
fed diets containing 0, 20 or 30% gum karaya for 3 months.
Histopathological examination of all organs at the termination of
the study showed no compound related effects (Balakrishan, 1984a).
Rats
Examination of the intestine of rats fed 1 g karaya gum per
day for 91 days showed no gross abnormalities. There was no
interference with normal growth (Ivy & Isaacs, 1938).
Karaya gum was used in a six- to seven-week feeding study to
evaluate the effect on adaptive responses of nutritionally
controlled parameters in rats by feeding a fibre-free diet
containing increasing additions of polysaccharides (0, 10, 20 and
40%). In general, the supplements reduced weight increases due to
lower energy intakes. None of the polysaccharides fed, however,
decreased energy utilization. Similarly, all polysaccharides
increased small intestine length up to about 30% without grossly
altering mucosal protein and DNA per unit of length. Concerning the
effect on the large intestine, the addition of karaya gum at 10, 20
and 40% level caused average increases of the weight of the colon
by a factor of 1.4, 1.9 and 2.9 respectively (Elsenhaus et al.,
1981).
Karaya gum given to groups of 15 rats of each sex at levels of
0 (control), 0.2, 1.0 and 5.0% (w/w) in the diet for 13 weeks (5%
is the top level recommended for substances that are not absorbed).
An increase in faecal bulk was seen in all treated groups
throughout the experiment. There was a decrease in weight gain at
the highest dietary level (significant only in the females) which
was associated with a marginal reduction in food conversion
efficiency. Males given 1 or 5% gum drank more than the controls
and a transient increase in water intake was seen in females given
the highest level. The no-effect level from this study was 5% of
the diet, providing a mean intake of approximately 4 g karaya
gum/kg bw per day (Taupin & Anderson, 1982).
Groups each of 16 rats (Wistar strain) equally divided by sex,
were maintained on diets containing 0, 0.5, 2 or 4% gum karaya for
90 days. Body weight, pattern and food intake was comparable for
all groups. At the termination of the study, creatine phosphate,
glutamic-oxaloacetic transaminase, glutamic pyruvic transaminase,
and protein was measured in serum and liver. Histopathology was
also carried out on the principle organs and tissues. No compound
related effects were observed (Dikshith et al., 1984).
Dogs
Three dogs were fed 5 g unprocessed karaya gum daily for 30
days. Faecal bulk and moisture were increased but there was no
obvious gastro-intestinal irritation (Ivy & Isaacs, 1938).
Long-term studies
Rats
Five rats were fed karaya gum in the diet for two years. Three
developed enlarged colons and ulcerations (Hoelzel et al., 1941).
In another experiment, groups of three rats were fed karaya
gum at first at 10%, gradually increasing to 25% in the diet over
their life span. Controls of five and seven animals received low
residue diets. No caecal ulceration was found in this experiment
(Carlson & Hoelzel, 1948).
Guinea pigs
Groups of Guinea pigs, distributed as 10 males and 8 females
in the test group, and 5 males and 5 females in the control group
were fed stock diet in which increasing amounts of the powdered gum
were incorporated, starting from 1 g level in the diet. The
increment of gum in the diet was continued up to obtaining 16.6%
level of gum (for the first 4 weeks). There after the 16.6% level
of gum in the stock diet was continued up to the termination of the
experiment at 52 weeks. Parameters investigated included growth,
excretion levels of N in urine, haematological values, organs
weight. At the end of treatment, organs such as heart, liver,
spleen, kidneys, adrenals were weighed and preserved for
histopathological observations. No compound related effects were
observed (Balakrishan, 1984b, National Institute of Nutrition
(India), 1985).
Rhesus monkeys
Four adult female rhesus monkeys (Macaca mulatta) were fed
diets containing gum karaya. Levels were progressively increased
over the course of one month, from 10 g to 25 g in a daily diet of
250 g (16.6%), and then maintained at this dietary level for 16
months. A control group of four female rhesus monkeys received
stock diet. Body weights, hematological data and liver function
tests were similar for test and control animals (Balakrishnan,
1984b, National Institute of Nutrition (India), 1985).
Eleven adult rhesus monkeys (5 males and 6 females) were
divided into two groups. The control group consisted of one male
and two female monkeys which were fed a basal stock diet. The
experimental groups consisted of four male and four female monkeys
which were fed a basal stock diet to which gum karaya at the 5% level
was added. The feeding trial was continued for a period of 18 weeks.
There was no difference in growth between the control and experimental
groups. There were some reduction in weight of control and experimental
male animals; it had no relation to the feeding of gum karaya. No
significant changes in the hematological parameters were found.
Absolute and relative weights of the various organs did not show
any change. The authors concluded that the organs and tissues of
the animals in the control and experimental groups were essentially
similar (Bhat et al., 1987).
Observations in man
Forty-six female and 46 male subjects took karaya gum granules
for one week at levels equivalent to 7 g/day. Seven subjects had
abdominal discomfort (Ivy & Isaacs, 1938).
Ingestion or inhalation was reported to have caused allergy.
Sixteen cases of allergic sensitivity to inhalation of the gum used
as wave set and to oral ingestion as a laxative were reported.
Symptoms included hay fever, asthma, dermatitis and gastro-
intestinal distress (Figley, 1940).
In a comparison with carob bean gum as a laxative in 10 human
subjects, karaya gum was found to be transformed to a gelatinous
state at a higher level in the intestine and to be transported more
rapidly through the intestinal tract (Holbrook, 1951).
A case of allergic respiratory symptoms (nasal congestion,
coughing and wheezing) following exposure to karaya gum powder has
been reported in a 27-year-old female nurse employed for three
years as an enterostomal therapist (Wagner, 1980).
The administration of karaya gum to human subjects and the
effects on glucose absorption and biochemical measurements were
studied. Karaya gum was administered to 5 healthy male volunteers
(aged 30-56 years), free of gastro-intestinal disease and symptoms,
over a 21-day period. The dose of 10.5 g was well tolerated. Karaya
gum had no significant effect on wet and dry stool weight, faecal
constituents or transit time. Also, there was no increase in
bactericidal metabolic activity. It would appear that the molecule
is not significantly degraded during its passage through the human
colon. Karaya gum appears to have little metabolic effect upon the
host: glucose tolerance is not significantly altered after its
ingestion and haematological and biochemical indices remain
unchanged (Eastwood et al., 1983).
Five male volunteers made 24-h collections prior to, and
following, the ingestion of 10 g gum karaya for 15 days. Paper
chromatographic separations, with two solvent systems, were made on
the fresh urine specimens and also after ten-fold enrichments of
all urinary constituents. Standard aqueous solutions of rhamnose,
and urine to which rhamnose had been added, showed the detection limit
to be 0.2 g rhamnose. Independent examinations on two laboratories
failed to detect rhamnose at this level in any of the urine
specimens. Had 1% of the rhamnose present in 10 g gum karaya
appeared in the 24-h urine specimens, it would have been detected.
This confirms previous evidence that dietary gum karaya is neither
digested nor degraded by enteric bacteria and is not absorbed to
any significant extent in man (Anderson et al., 1985a).
Gum karaya (10 g) was added to the normal diet of 5
participating male volunteers with ages ranging from 21 to 57
years. A series of urinary, blood and faecal analyses were made
during an initial control period of 7 days and for a further 7 days
during the third week of the supplemented diet period. Gum karaya
had no effect on stool weight, serum cholesterol or hydrogen in
expired air (Eastwood et al., 1986).
Eleven men, age 23-62 years (averaging 38 years and 86.0 kg
bw) consumed a basal diet with a relatively low fiber 4 day
rotating menu containing 6.33 g neutral detergent fiber per
2550 kcal throughout the 20-week study. Four refined fibers, locust
bean gum (LBG), karaya gum (KG), carboxymethylcellulose gum (CMC), and
cellulose, were used as the fiber sources. Each fiber source was
added to the basal diet in the form of baked muffins or fruit juice
gel for 4 wk at 7.5 g of refined fiber per 1000 kcal. Refined fiber
intake ranged from 19.1 g/d to 26.0 g/d depending on caloric
intake. Food, urine and faecal composites were collected during the
last 8 d of each feeding period. Bowel transit time was not
significantly affected; however total dry fecal weight was
significantly increased after administration of the refined fiber
diet compared with that after the basal diet. Adding refined fibers
to the basal diet did not significantly affect apparent mineral
balance of calcium, magnesium, manganese, iron, copper or zinc,
with the exception of a negative mineral balance for manganese with
carboxymethylcellulose. Karaya gum had a mean positive balance for
all minerals tested (Behall et al., 1987).
COMMENTS
The Committee considered that the data provided additional
information on the lack of toxicity of karaya gum when fed at high
dietary levels. The analysis of the gum revealed that there are no
unusual amino acids present. Karaya gum is not degraded by strains
of bacteria found in the human colon and does not undergo any
metabolic modification in the intestinal tract of rats and dogs.
Studies in both rats and human subjects failed to detect rhamnose
in the urine of both species, suggesting that the gum is neither
digested nor degraded by enteric bacteria. A short-term study in
rats showed no evidence of adverse effects at the 5% level. Dietary
studies in man indicate that karaya gum is tolerated for 21 days at
dose levels of 10.5 g/day without any adverse effect.
EVALUATION
Estimate of Acceptable Daily Intake for Man
ADI "not specified".
Further work or information
Desired
Detailed histopathological information on the monkey studies.
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See Also:
Toxicological Abbreviations
Karaya gum (FAO Nutrition Meetings Report Series 46a)
Karaya gum (WHO Food Additives Series 5)
Karaya gum (WHO Food Additives Series 18)
KARAYA GUM (JECFA Evaluation)