ARABIC GUM (Gum Arabic)
Explanation
This substance was last evaluated for acceptable daily intake for
man by the Joint FAO/WHO Expert Committee on Food Additives in 1969
(see Annex I, Ref. 19). A toxicological monograph was issued in 1970
(see Annex I, Ref. 20).
Additional data have become available and are summarized and
discussed in the following monograph. The previous monograph has been
expanded and is reproduced in its entirety below.
BIOLOGICAL DATA
BIOLOGICAL ASPECTS
Absorption and metabolism
Based on food and caloric intake, arabic gum fed to weanling male
Sprague-Dawley rats at dietary levels of 0.5 and 2.0 g/day was
reported to have caloric values of 131% and 110% of corn starch,
respectively (Nees, 1965).
Arabic gum is almost completely digested by guinea-pigs (O'Dell
et al., 1957).
At dietary levels of less than 10%, arabic gum is fully absorbed
with a caloric equivalent of 4 calories per gram (Shue et al., 1962).
Effects on enzymes and other biochemical parameters
Groups of female ZUR:SIV-Z strain rats, initial body weight
100-110 g, were gavaged twice daily, 5 days per week for 4 weeks with
20, 40 or 200 mg/kg of arabic gum as an aqueous suspension. Groups
of 4 rats were killed at various time intervals and oxidative
phosphorylation in isolated liver and heart mitochondria was assayed
as well as mixed function oxidase activity in liver endoplasmic
reticulum. A dose-dependent uncoupling of oxidative phosphorylation in
heart and liver mitochondria was reported in the arabic gum groups.
significant reductions occurred within 2 days to 2 weeks depending on
the dose. As the feeding of arabic gum continued, liver mitochondria
isolated from test animals appeared to recover. Recovery did not occur
in the isolated heart mitochondria at the mid-dosage level. At the
high-dose level as feeding of test animals continued, there was
partial recovery in the isolated heart mitochondria followed by
another decline. The mid- and high-dose levels of arabic gum were
reported to cause a progressive decline in hepatic mixed function
oxidase activity, while no effect was noted at the low dose (Bachman
et al., 1978).
Another study similar to the preceding one was carried out in
female rats (ZUR:SIV-Z strain), golden hamsters (ZUR:LAK-Z strain),
and mice (ZUR;ICR-Z strain). In mice and hamsters, there was an
initial decrease in hepatic biphenyl hydroxylation; however, enzyme
activity returned towards control values as the experiment progressed.
In the rat, biphenyl hydroxylase activity went down and did not
recover. Hepatic cytochrome b5 and P450 levels were also measured;
levels of these proteins were not affected by arabic gum dosing in the
rat. However, cytochrome b5 levels were depressed by the treatment in
hamsters, while in mice there was a transient decrease in both
cytochrome P450 and b5 levels (Bachman & Zbinden, 1978).
Female rats (ZUR:SIV-Z strain) dosed by gavage with 200 mg/kg of
gum arabic twice daily for 3 or 4 days showed an inhibition of
phenobarbitol-stimulated aminopyrine demethylation as compared to
animals not receiving gum arabic (Lutz et al., 1978).
Groups of 10 Sprague-Dawley rats received 0 or 5% of arabic
gum in a 0.2% cholesterol-supplemented diet. A tracer dose of
14C-labelled cholesterol was included in the animals' last meal. The
animals fed arabic gum had significantly lower absorption of labelled
cholesterol, although there was no effect on total carcass, serum or
liver concentrations of cholesterol. However, uptake of 14C-labelled
cholesterol in liver and carcass was reduced. Arabic gum was
associated with an increase in total cholesterol biosynthesis (Kelly &
Tsai, 1978).
TOXICOLOGICAL STUDIES
Special studies on carcinogenicity
Mouse
Groups of 50 male and 50 female B6C3F1 mice were given arabic gum
in the diet at concentrations of 0, 25 000 or 50 000 ppm (0, 2.5 or
5.0%) for 103 weeks. The animals were maintained on a control diet for
an additional 2 weeks prior to sacrifice. No effect of the test
compound on body weight gain was noted in either sex, although mean
daily food consumption was reduced in both sexes of the groups
receiving arabic gum. No effect of the test compound was noted with
respect to survival, clinical signs, or incidence of gross or
microscopic non-neoplastic lesions. Hepatocellular adenoma of the
liver was found in 2/49 controls, 0/50 low-dose and 6/49 high-dose
females. Hepatocellular carcinomas were found in 1/49 controls, 2/50
low-dose and 6/50 high-dose females. The number of female mice with
hepatocellular adenoma, carcinoma or unspecified neoplasm of the liver
were 4/49, 2/50 and 10/49 in controls, low-dose and high-dose animals,
respectively. Some high-dose animals had both a hepatocellular adenoma
and a hepatocellular carcinoma. The historical records at the
performing laboratory indicate the incidence of control female B6C3F1
mice with adenomas or carcinomas of the liver has been 56/975 (5.7%)
with a range of 1/50 to 11/54 (2-20.3%). Male mice given arabic gum
did not have an increased incidence of liver tumours. The incidence of
mice with haemangiomas or haemangiosarcomas of the circulatory system
was not significant in either sex. The conclusion of the study was
that there was no site at which an increase in tumour incidence could
be clearly associated with the administration of the chemical
(National Toxicology Program, 1980).
Rat
Groups of 50 male and 50 female Fischer 344 rats were given gum
arabic in the diet at concentrations of 0, 25 000 or 50 000 ppm
(0, 2.5 or 5.0%) for 103 weeks. The animals were maintained on the
control diets for an additional 2 weeks prior to sacrifice. In the
males, body weights of test and control animals were comparable
throughout the study, while in the females, weight gain in the test
animals was slightly less than that of controls. The effect was not
dose related. As compared to controls, feed intake was reduced in test
males and test females. No effects of the test compound were reported
with respect to clinical signs, survival, or incidence of gross or
microscopic lesions (National Toxicology Program, 1980).
Special studies on mutagenicity
Gum arabic did not produce a measurable mutagenic response or
alteration in the recombination frequency for Saccharomyces
cerevisiae in either the host-mediated assay or in vitro.
Similarly, no mutagenicity was reported with gum arabic either in the
host-mediated assay or in vitro using Salmonella strains G-46 or
TA-1530.
Cultures of bone marrow metaphase chromosomes taken from rats
dosed in vivo with 50 mg or 2.5 g/kg of arabic gum showed an
increased incidence of chromosomal breaks occurring within 6 hours of
treatment. Similar effects were found in vitro with human WI-38
embryonic lung cells.
Gum arabic was tested using the dominant lethal gene test in
Sprague-Dawley rats. Males were given 0, 30, 2500 or 5000 mg/kg by
gavage in a water suspension. A significant increase in dead implants
was noted in pregnant females mated to males given a single dose of
5000 mg/kg at the third week of the study. No other significant
effects were recorded and arabic gum was considered not to be a
mutagen in this study (Newell & Maxwell, 1972).
No genetic activity was noted in in vitro mutagenic tests with
Saccharomyces cerevisiae strain D4 and Salmonella typhimurium
strains TA-1535, TA-1537 and TA-1538. Both suspension and plate test
were used, with and without activation. Activation systems were
prepared from liver, lung, kidney and testes from male mice, rats and
monkeys (Brusick, 1975).
Gum arabic was concluded to be not mutagenic based on the sex-
linked dominant lethal test in Drosophila (Valencia & Abrahamson).
Special observations on sensitivity
Sensitivity to arabic gum was found to be a true antigen-antibody
response in the guinea-pig (Rice, 1955; Silvette et al., 1955).
Special studies in teratology
Groups of 21-24 pregnant Wistar-derived rats were dosed by gavage
on days 6 through 15 of gestation with 0, 16, 75, 350 or 1600 mg/kg of
arabic gum suspended in corn oil. No compound-related effect was
observed on nidation, maternal or foetal survival, or on the incidence
of hard or soft tissue anomalies occurring in the offspring. The
average foetal weight at birth was slightly depressed in the high-dose
group.
Groups of 19-21 pregnant CD-1 mice were dosed by gavage on days 6
through 15 of gestation with 0, 16, 75, 350 or 1600 mg/kg of arabic
gum suspended in corn oil. No compound-related effect was observed on
nidation, maternal or foetal survival or on the incidence of hard or
soft tissue anomalies occurring in the offspring. The average foetal
weight at birth was slightly depressed in the high-dose group.
Groups of 19-21 pregnant outbred golden hamsters were dosed by
gavage on days 6 through 10 of gestation with 0, 16, 75, 350 or
1600 mg/kg of arabic gum suspended in corn oil. No compound-related
effect was observed on nidation, maternal or foetal survival or on the
incidence of hard or soft tissue anomalies occurring in the offspring.
Groups of 12-14 pregnant Dutch-belted rabbits were dosed by
gavage with 0, 8, 37, 173 or 800 mg/kg of arabic gum suspended in corn
oil on days 6 through 18 of gestation. The administration of up to
37 mg/kg of the test material as a suspension in anhydrous corn oil
had no clear effect on nidation or on maternal or foetal survival.
The number and type of abnormalities seen in foetal soft or skeletal
tissues derived from this group of does did not differ from the number
occurring spontaneously in the sham-treated controls. However, in 2
groups of dams dosed at 173 and 800 mg/kg bw respectively, maternal
toxicity ensued with the loss of a majority of animals in the
800 mg/kg group. Death was preceded by severe bloody diarrhoea,
urinary incontinence, with anorexia for 48-72 hours terminally. At
autopsy no gross pathological findings were seen other than
haemorrhage in the mucosa of the small intestines. Does which survived
the highest dose and bore living young to term remained outwardly
normal, and the offspring were likewise normal in all respects. It was
concluded that this test substance was not a teratogen in the rabbit
under the test conditions employed (Morgareidge, 1972).
Acute toxicity
LD50
Animal Route (g/kg bw) Reference
Mouse Oral 16.0 Morgareidge, 1972
Rat Oral 18.0 Morgareidge, 1972
Hamster Oral 16.0 Morgareidge, 1972
Rabbit Oral 8.0 Morgareidge, 1972
Short-term studies
Mouse
Groups of 10 male and 10 female B6C3F1 mice were fed diets
containing 0, 6300, 12 500, 25 000, 50 000 or 100 000 ppm (0, 0.63,
1.25, 2.5, 5.0 or 10%) of arabic gum in the diet for 13 weeks. No
compound-related effects on survival or gross or microscopic pathology
were noted. Final body weights and feed consumption tended to be
slightly lower in the dosed animals (National Toxicology Program,
1980).
Rat
Groups of rats were fed 0 or 15% arabic gum in their diet for 62
days. A cathartic effect was observed, but weight gain, food
efficiency, haematological findings and organ weights were normal
(Booth et al., 1963).
Groups of 10 male and female Fischer 344 rats were fed diets
containing 0, 6300, 12 500, 25 000, 50 000 or 100 000 ppm (0, 0.63,
1.25, 2.5, 5.0 or 10%) gum arabic in the diet for 13 weeks. No
compound-related effects on survival or gross or microscopic pathology
were noted. Feed consumption was reduced at the 2 highest doses in the
males, and at all the doses in the females. Final body weights tended
to be slightly lower in the dosed animals (National Toxicology
Program, 1980).
Guinea-pig
Groups of 10 and 20 guinea-pigs were fed 15% powdered arabic gum
for 6 weeks. Controls received no bulk food in their diet. Weight gain
was improved in the test groups (Booth et al., 1949).
Rabbit
A group of 4 rabbits was given 20% arabic gum in a casein diet
for 4 weeks. Weight gain improved significantly in the test groups
(Hove & Herndon, 1957).
Dog
Three dogs were given 32-35 intravenous injections of acacia over
a period of 76 days at a total cumulative dosage ranging from 15.7 to
47.7 g/kg. The dog on the largest dose died with an enlarged liver.
Cause of death, 4 months after its last injection, was not explanable.
The other two dogs remained in good condition; biopsy showed acacia
present in their livers 26 months after their last injections (Smalley
et al., 1945).
Man
Nine patients with nephrotic oedema received 1-6 intravenous
injections of acacia over periods up to 8 weeks, with total doses
ranging from 80 to 325 g. There were no signs or symptoms of liver
enlargement, and no other complications. Five of these patients
excreted in the urine 5.5-38% of a single dose during periods ranging
from 10 to 30 days, respectively (Johnson & Newman, 1945).
OBSERVATIONS IN MAN
Sensitivity reactions have been reported in man, e.g., asthma in
printers (Brown & Crepea, 1947; Bohner et al., 1941; Sprague, 1942;
Fowler, 1952).
Occupational exposure to arabic gum has been associated with
rhinitis and asthma in sensitive individuals (Cuthbert, 1973).
Sensitivity to arabic gum as a tablet additive has been reported
in some kidney transplant patients. Hypersensitivity manifested as
itching, and rash with fever and arthralgia was also reported in
individual patients (Rubinger et al. 1978). Sensitivity of some
individuals to gum arabic in food has also been reported (Gelfand,
1949).
Comments
Metabolic studies are limited, but it has been demonstrated that
in the rat this gum is completely metabolized when it comprises less
than 10% of the diet. Mitochondrial preparations isolated from the
liver or hearts of rats maintained on diets containing arabic gum
showed a dose- and time-dependent uncoupling of oxidative
phosphorylation. Hepatic mixed function oxidase activity was also
depressed. Changes were also reported in hepatic cytochrome b5 and
P450 levels in the liver of test animals maintained on diets
containing arabic gum. The significance of these effects is not known,
since inclusion of arabic gum in the diet of test animals at levels
that cause these effects does not cause a reduction in weight gain,
which would be expected if uncoupling of oxidative phosphorylation
occurred.
Teratology studies were negative in rats, mice, hamsters and
rabbits, although maternal toxicity was observed at very high dose
levels in the rabbit.
Mutagenic studies in a number of systems, including host-mediated
assay, the Ames test, Saccharomyces cerevisiae, dominant lethal test
and Drosophila, were negative. Lifetime feeding studies in the rat and
mouse at 5% of the diet showed no significant adverse effects.
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
Bachman, E. et al. (1978) Biochemical effects of gum arabic gum,
tragacanth, methylcellulose and carboxymethylcellulose in the rat
heart and liver, Pharmacol., 17, 39-49
Bachman, E. & Zbinden, G. (1978) Biochemical effects of chronically
administered suspended agents on mitochondrial metabolism and
hepatic mixed function oxidases in rat, mice and hamster, Arch.
Toxicol. Suppl., 1, 183-187
Bohner, C. B., Sheldon, J. M. & Trenis, J. W. (1941) Sensitivity of
gum acacia with a report of ten cases of asthma in printers,
J. Allergy, 12, 290
Booth, A. N., Elvehjem, C. A. & Hart, E. B. (1949) The importance of
bulk in the nutrition of the guinea pig, J. Nutr., 37, 263
Booth, A. N., Hendrickson, A. P. & De Eds, F. (1963) Physiologic
effects of three microbial polysaccharides on rats, Toxicol.
Appl. Pharmacol., 5, 478
Brown, E. B. & Crepea, S. B. (1947) Allergy (asthma) to ingested gum
tragacanth - a case report, J. Allergy, 18, 214
Brusick, E. (1975) Mutagenic evaluation of compound FDA 71-15, gum
arabic. Unpublished. Litton Bionetics, Inc. Contract, 32 pp.
Contract No. 223-74-2104. Submitted to the World Health
Organization by the US Food and Drug Administration
Cuthbert, O. D. (1973) Investigation into an outbreak of rhinitis and
asthma in a printing works, Ann. Occup. Hyg., 16, 203
Fowler, P. B. S. (1952) Printer's asthma, Lancet, 2, 755
Gelfand, H. H. (1949) The vegetable gums by ingestion in the etiology
of allergic disorders, J. Allergy, 20, 311-321
Hove, E. L. & Herndon, F. J. (1957) Growth of rabbits on purified
diets, J. Nutr., 63, 193
Johnson, J. B. & Newman, L. H. (1945) Intravenous injection of acacia,
Arch. Intern. Med., 76, 167
Kelly, J. & Tsai, A. (1978) Effects of pectin, gum arabic and agar on
cholesterol absorption, synthesis and turnover in rats,
J. Nutr., 108, 630-639
Lutz, W. K., Braudle, E. & Zbinden, G. (1978) Effect of gum arabic on
aminopyrine demethylation in rats, Experientia, 34, 1609-1610
Newell, G. W. & Maxwell, W. A. (1972) Study of mutagenic effects of
gum arabic. Unpublished. Standard Research Institute, pp. 31.
Contract No. FDA 71-267. Submitted to the World Health
Organization by the US Food and Drug Administration
Morgareidge, K. (1972a) Acute toxicity studies on gum arabic.
Unpublished. Food and Drug Research Laboratories, Inc. Contract
No. FDA 71-260. Submitted to the World Health Organization by the
US Food and Drug Administration
Morgareidge, K. (1972b) Teratologic evaluation of FDA 71-15 (gum
arabic). Unpublished. Food and Drug Research Laboratories, Inc.
Contract No. FDA 71-260. Submitted to the World Health
Organization by the US Food and Drug Administration
National Toxicology Program (1980) Carcinogenesis bioassay of gum
arabic. Unpublished. National Toxicology Program, Research
Triangle Park, North Carolina, pp. 134. Submitted to the World
Health Organization by the US Food and Drug Administration
Nees, P. W. (1965) Hallmark pure gum arabic No. 1 U.S.P. - evaluation
of caloric content. Unpublished. In: Wisconsin Alumni Foundation,
Madison, Wisconsin, pp. 3, (Assay Report No. 4121036. Submitted
to the World Health Organization by the US Food and Drug
Administration
O'Dell, B. L. et al. (1957) Diet composition and mineral balance in
guinea pigs, J. Nutr., 63, 65
Rice, C. E. (1955) An investigation of some of the factors determining
the decrease in complement activity in anaphylactic shock,
J. Immunol., 75, 85-95
Rubinger, D., Friedlander, M. & Superstine, E. (1978) Hypersensitivity
to tablet additives transplant recipients on prednisone,
Lancet, 2, 689
Silvette, M., Swinford, O., Jr & Tull, L. (1955) Observations on
acacia as an immunizing, sensitizing anaphylactogenic and
desensitizing antigen, J. Allergy, 26, 509-518
Shue, G. M., Douglass, C. D. & Friedman, L. (1962) Nutritional studies
of complex carbohydrates, Fed. Proc., 21(2), 91
Smalley, R. E. et al. (1945) Effect of intravenously administered
solution of acacia on animals, Arch. Intern. Med., 76, 39
Sprague, P. H. (1942) Bronchial asthma due to sensitivity to gum
acacia, Canad. Med. Ass. J., 47, 253
Valencia, R. & Abrahamson, S. (undated) Drosophila sex-linked
recessive lethal test on gum arabic. Unpublished. Contract No.
FDA 223-77-2119, pp. 4. Dept. of Zoology, University of
Wisconsin. Submitted to the World Health Organization by the US
Food and Drug Administration
See Also:
Toxicological Abbreviations
Arabic gum (FAO Nutrition Meetings Report Series 46a)
Arabic gum (WHO Food Additives Series 5)