CAROB (LOCUST) BEAN GUM
Explanation
This substance was evaluated for acceptable daily intake for man
by the Joint FAO/WHO Expert Committee on Food Additives in 1969, 1973
and 1975 (see Annex, Refs. 19, 32 and 37). Toxicological monographs
were issued in 1970, 1974 and 1975 (see Annex, Refs. 20, 30 and 38).
Additional data have become available since the previous
evaluation and are summarized and discussed in the following
monograph. The previous monograph has been expanded and is reproduced
in its entirety below.
Introduction
Carob bean gum (also called locust bean gum) is the material
separated and variously refined from the endosperm of the seed of the
carob tree, Ceratonia siliqua, a large leguminous evergreen that
is widely cultivated in the Mediterranean area. The carbohydrate
component of carob bean gum is considered to be a neutral
galactomannan polymer consisting of a main chain of 1,4-linked
D-mannose units with a side chain of D-galactose on every fourth or
fifth unit, attached through 1,6-glycosidic linkages to the
polymannose chain (LSRO/FASEB, SCOGS-3, 1972).
BIOLOGICAL DATA
BIOCHEMICAL ASPECTS
In a bioavailable calorie assay, groups of 10 male weanling rats
(Sprague-Dawley) were given 5 g basal diet or basal diet plus 0.5, 1,
2 g sucrose or 0.5, 1, 2 g gum for 10 days. Comparison of the carcass
weight gain showed that carob bean gum was not a source of
bioavailable calories (Robaislek, 1974).
Fifteen controls and 18 male test rats, after three days on
normal diet followed by a 12-hour fast, received for two-and-a-half
days in their diet either 67% cocoa butter with wheat flour or 67%
cocoa butter with 33% carob bean gum. Glycogen accumulated in the
liver but far less efficiently than with wheat flour (Krantz et al.,
1948).
A digestibility study in groups of five male and five female rats
(Purdue strain) on a mannose-free diet showed that 85-100% of mannose
fed as 1% carob bean gum in the diet for 18 hours were excreted in the
faeces over a total of 30 hours. Some decrease in chain length of
galactomannan may have occurred, probably through the action of the
microflora as mammals are not known to possess mannosidase. Liberation
of galactose units was not determined (Tsay & Whistler, 1975).
Incubation of solutions or suspensions with human gastric juice,
duodenal juice plus bile, pancreatic juice and succus entericus with
or without added rabbit small gut membrane enzymes produced no
evidence of hydrolysis (Semenza, 1975). Rat large gut microflora
partially hydrolysed carob bean gum in vitro (Towle & Schranz, 1975)
after conditioning to 14 carob bean gum in the diet for three weeks.
Groups each of eight male Holtzman rats were maintained on a
purified synthetic diet, or the diet plus 1% cholesterol, or the diet
plus 1% cholesterol plus 10% carob bean gum for 28 days. The increased
liver cholesterol and liver total lipid induced by cholesterol feeding
was largely counteracted by concurrent feeding of carob bean gum
(Ershoff & Wells, 1962).
Groups each of 12 chicks, one day old, were fed a casein sucrose
basal diet supplement with 34 cholesterol and either 10, 6, 3, 2, 1.5
or 1.0% locust bean gum for 27 days. At the end of the test period,
plasma cholesterol was determined. At the 10% level, there was a 35%
reduction of plasma cholesterol, no significant effect in body
weight or food consumption. At the 64 level, there was a moderate
reduction in cholesterol level. There was a wide variation in the
hypocholesterolaemic activity of the carob bean gums tested with some
preparations being totally inactive (Fahrenbach et al., 1966).
The effect of carob or locust bean gum on nitrogen (N) balance
and dry matter digestibility was studied in rats. Seventy-two weanling
male Sprague-Dawley rats were divided into a control and five
experimental groups of 12 animals each. Various gums including locust
bean gum were fed at the 10% level in a casein-saccharose-corn starch
diet. Following a three-day adaptation period, feed remnants, urine
and faeces were collected during an eight-day balance period. Trypsin
inhibitory activity was measured in each diet. Carob bean gum caused a
significant rise in faecal N loss, resulting in a marked reduction of
apparent protein digestibility from 87.8% in the controls to 75%.
Urinary N was significantly lower than controls. Faecal dry matter was
also significantly increased by carob bean gum. There was only slight
trypsin inhibition caused by carob bean gum (Harmuth-Hoene &
Schwerdtfeger, 1979).
Carob bean gum has been noted to contain tannins, which depress
appetite and growth, and trypsin inhibitors, which are also growth
inhibitory (LSRO/FASEB, SCOGS-3, 1972).
TOXICOLOGICAL STUDIES
Special studies on mutagenicity
Carob (locust) bean gum was evaluated for genetic activity in
microbial assays with and without the addition of mammalian metabolic
activation preparations. Indicator organisms used were Saccharomyces
cerevisiae and Salmonella typhimurium, strains TA-1535, TA-1537
and TA-1538. Mammalian metabolic activation preparations were from
mouse (ICR adult), rat (Sprague-Dawley adult) and monkey (Macaca
mulatta adult). Carob (locust) bean gum did not exhibit genetic
activity in any of the assays employed (Litton Bionetics, 1975;
Maxwell & Newell, 1972).
Special studies on reproduction
A three-generation reproduction study was carried out in CD
strain Charles River albino rats. Groups of 10 male and 20 female
animals were fed a rat chow diet containing 2 or 5% locust bean gum
(LBG) or 5% alpha cellulose (control). The same doses and animal
numbers were used throughout the study. In each generation the
parental animals received the test diet for 11 weeks prior to mating
and then through mating, gestation and weaning.
Two or three litters were raised per generation and the second
litter was used to produce the following generation. Ten males and 10
females from each treatment group of the F3b generation were selected
for histopathological examination of 12 major organs and tissues and
organ weight analysis. All other animals were subject to gross
necropsy only.
There were statistically significant decreases in premating body
weight gain in the F0 females fed 2% LBG and in final body weight in
the females fed 5% LBG.
There were the following significant differences in organ weight
ratios in the F3b 5% LBG group as compared to the controls: smaller
spleen to brain weight, absolute liver weight, liver to brain weight
and larger brain to body weight. These differences were ascribed to
the highly variable values for these parameters in young rats and the
fact that all the animals may not have been at the same age at
sacrifice. This factor could have had an effect on organ weight ratios
in young animals.
There were no significant treatment-related effects on
reproductive indices or gross or microscopic pathology (Domanski et
al., 1980).
Special studies on teratogenicity
Teratogenic experiments with four species of animals (rats, mice,
hamsters and rabbits) did not indicate that the test material was a
teratogen to mice at 280 m/kg bw and 1300 mg/kg, although 5/21 dams
died at the latter dose. Up to 1300 mg/kg in rats, up to 1000 mg/kg in
hamsters and at 196 mg/kg in rabbits no teratological effects were
seen. At 910 mg/kg in rabbits, most of the pregnant dams died
(Morgareidge, 1972).
Carob bean gum was injected via the air cell and yolk or albumen
route into fertile eggs prior to and after 96 hours of incubation.
Eggs were candled at 48-hour intervals and dead embryos were examined
for stage of development and defects. At hatching, all chicks were
examined for gross defects and samples were taken for gross skeletal
staining and histopathological examination. Although the authors do
not state levels of carob bean gum injected, they note anophthalmia,
phocomelia, micromelia and torticollis occurring with carbob bean gum
(Naber & Smothers, 1975).
Acute toxicity
LD50
Animal Route (g/kg bw) Reference
Mouse Oral (gavage 13.1 ± 0.65 Maxwell & Newell, 1970
in corn oil)
Hamster Oral (gavage 10.3 ± 0.49 Maxwell & Newell, 1970
in corn oil)
Rat Oral (gavage 13.1 ± 0.75 Food & Drug Research
in corn oil) Laboratories, Inc., 1976
Oral (gavage 5.00 Maxwell & Newell, 1970
in corn oil)
Rabbit Oral (gavage 9.1 ± 0.39 Maxwell & Newell, 1970
in corn oil)
Short-term studies
Rat
Groups of 10 males and 10 females were fed in their diet carob
bean gum at levels of 0, 1, 2 or 5% for 90 days. General condition,
behaviour, survival, growth, food intake, haematology, blood
biochemistry and urinalysis showed no treatment-related differences
between test and control groups at any dietary level except that the
last glucose level was slightly increased in the 5% group. Gross and
microscopic examination did not reveal any pathological changes
attributable to ingestion of the gum. The increase in the relative
weight of the caecum at the 2% level is not considered to be of
toxicological importance (Til et al., 1974).
Groups of newly weaned Sprague-Dawley rats (10 per group) were
fed a soybean-corn meal diet containing 2% locust (carob) bean gum for
36 days. Locust bean gum had no effect on the digestibility of the
diet, nor was there any significant effect on growth (Vohra et al.,
1979).
Dog
Four groups of five male and five female beagles were fed 0, 1, 5
or 10% of a precooked mixture of carob bean and guar gum (proportions
unknown) for 30 weeks. Only at the 10% level were hypermotility and
soft, bulky stools observed, probably of no toxicological
significance. Also at the 10% level digestibility was reduced. No
adverse haematological, urinary, gross and histopathological and
ophthalmological findings were noted (Cox et al., 1974).
Chicken
Groups of 20-day-old chickens were fed diets containing 0.25,
0.52, 12 and 22% carob bean gum for three weeks. Growth depression was
dose related and marked at the 2% level of intake (Kratzer et al.,
1967; Vohra & Kratzer, 1964).
Groups of day-old broiler chickens (seven per group, breed not
specified) were fed a soybean protein-corn based diet containing 2%
carob (locust) bean gum for 24 days. The dietary intake of the
chickens was measured daily for the last week of the experimental
period; digestibility of the test diet was calculated from the dry
weights of the feed and excreta. The average body weight of chickens
and the digestibility of the diet was reduced significantly by the
inclusion of locust (carob) bean gum in the diet (Vohra et al., 1979).
Japanese quail
Groups of day-old Japanese quail (10 per group) were fed a
soybean-meal-corn based diet containing 2% locust (carob) bean gum
for either 35 or 37 days. The dietary intake of the quail was measured
daily for the last week of their experimental period; the
digestibility of the diet was calculated from the dry weights of the
feed and excreta. Average body weight and digestibility of the diet
was significantly reduced by inclusion of locust (carob) bean gum in
the diet (Vohra et al., 1979).
Long-term studies
Mouse
Groups of 50 male and 50 female B6C3F1 mice were given 0, 25 000
or 50 000 ppm (0, 2.5 or 5%) carob bean gum in the diet for 103 weeks.
The surviving animals were then fed a control diet for an additional
two weeks prior to sacrifice. The mean body weight of the high dose
male mice was lower than the control during the second year of the
study. The other dose groups had body weights comparable to their
respective control groups. No significant compound-related effects
were noted with respect to survival or gross or microscopic pathology
except for the possible incidence of alveolar/bronchiolar adenomas in
male mice. The incidence of this lesion was 7/50 in the control, 17/50
in the low dose group and 11/50 in the high dose group. The historical
incidence of this lesion in male mice was 8.1%, although incidences in
the test laboratory performing the study had ranged upwards of 26%.
The investigators concluded that "the lack of significant results in
the high dose group taken together with the relatively high background
rate of these tumors precludes a clear decision as to the effect of
locust bean gum at this site. When the incidence of male mice with
adenomas or carcinomas is analyzed, there is no significant result".
The report concluded that locust bean gum was not carcinogenic to male
or female rats or mice under conditions of the test (National
Toxicology Program, 1980).
Rat
Fischer 344 rats in groups of 50 animals/sex were fed 0, 25 000
or 50 000 ppm (0, 2.5 or 5%) carob bean gum in the diet for 103 weeks;
the surviving animals were then fed the control diet for an additional
two or three weeks prior to sacrifice. No compound-related effects
were noted on body weights, survival, or gross or microscopic lesions.
Groups of 50 male and 50 female Charles River strain albino rats
were fed diets containing 5% alpha cellulose (control) or 2 or 5%
carob bean gum (CBG) for 24 months. There was an interim sacrifice of
10 animals/sex/dose carried out at 12 months.
Significantly greater body weights in the 2% CBG females were
observed at weeks 11, 94, 95, 96, 97, 98, 99 and 100 of the study and
at week 13 in the 5% CBG females. Numerous significant differences in
food consumption were observed during the study, but these were
ascribed to the spillage of the control diet. Inclusion of alpha
cellulose in the diet was said to result in physical characteristics
which made spillage control very difficult.
The following significant differences with respect to haematology
measurements were noted: decrease in reticulocyte count in 5% CBG
females at six months; decrease in haemoglobin concentration in 2% CBG
female rats at six months; and increase in segmented neutrophils and
decrease in lymphocytes in 2% male rats at six months.
A statistically significant reduction in absolute thyroid weight
was noted in the 2% and 5% male CBG groups at the interim sacrifice. A
significant reduction in absolute brain weight was cited in the 5% CBG
females at the final sacrifice.
No significant treatment-related effects on gross or microscopic
pathology were reported (Carlson & Domanski, 1980).
OBSERVATIONS IN MAN
A clinical study of a commercial preparation of carob bean grain
as a laxative in doses of "two heaping teaspoonfuls" in 56 patients,
some of whom took the preparation regularly for two years, resulted in
no untoward effects related to the gastrointestinal tract, and no
allergenic reaction (Holbrook, 1951).
Eight infants between the ages of two-and-a-half to five months
were fed meals of sugared milk or sugared milk plus a 1% powder
extract from carob bean. Addition of the carob supplement did not
alter the duration of the gastrointestinal transit time of the meal.
Physiological aerophagy was markedly suppressed by the supplement
(Rivier, 1952).
Comments
In vitro tests with human enzyme preparations show little
utilization by the gut. Carob bean gum was not teratogenic in several
mammalian species although it did produce terata in the chick embryo
assay. The available short-term studies in the rat and dog showed no
evidence of adverse effects at the 5% level. The effects noted in
feeding trials are those expected of a non-metabolized polymeric
substance acting as a bulking agent. In the previous evaluation, it
was noted that the following studies were not available for
evaluation: long-term, reproduction, teratogenicity and mutagenicity.
The new data submitted showed that carob bean gum did not cause any
significant compound-related effects in a three-generation
reproduction study. It was not mutagenic in microbial systems, with
and without activation. In lifetime feeding studies in the rat and
mouse, carob bean gum was not carcinogenic.
EVALUATION
ADI 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
Carlson, W. & Domanski, J. (1980) Two year chronic oral toxicity study
with locust bean gum in albino rats. Unpublished study.
Industrial Bio-Test Laboratories, Inc.
Cox, G. E., Baily, D. E. & Morgareidge, K. (1974) Subacute feeding in
dogs with a pre-cooked gum blend. Unpublished report from the
Food and Drugs Laboratories, Inc., submitted to the World Health
Organization by Hercules BV
Domanski, J., Carlson, W. & Frawley, J. (1980) Three generation
reproduction study on locust bean gum in albino rats. Unpublished
study
Ershoff, B. H. & Wells, A. G. (1962) Effects of gum guar, locust bean
gum and carrageenan on liver cholesterol of cholesterol-fed rats,
Proc. Soc. Exp. Biol. Med., 110 (3), 580-582
Fahrenbach, M. J., Riccardi, B. A. & Grant, W. E. (1966)
Hypocholesterolemic activity of mucilaginous polysaccharides in
White Leghorn cockerels, Proc. Soc. Exp. Biol. Med., 13 (2),
321-326
Food & Drug Research Laboratories, Inc. (1972) Teratologic evaluation
of FDA 71-14. Teratologic evaluation of carob bean (locust) gum.
Submitted under Contract No. FDA 71-260. Maspeth, N.Y.
Harmuth-Hoene, A. & Schwerdtfeger, E. (1979) Effect of indigestible
polysaccharides on protein digestibility and nitrogen retention
in growing rats, Nut. Metab., 23, 399-407
Holbrook, A. A. (1951) The behaviour of carob bean in the
gastrointestinal tract of man, Amer. J. Dig. Dis., 18, 24-28
Krantz, J. C., jr, Carr, C. J. & De Farson, C. B. (1948) Guar poly-
saccharide as a precursor of glycogen, J. Amer. Diet Ass.,
24, 212
Kratzer, F. H., Rajaguru, R.W.A.S.B. & Vohra, P. (1967) The effect
of polysaccharides on energy utilization, nitrogen retention and
fat absorption in chickens, Poultry Sci., 48, 1489-1493
Litton Bionetics, Inc. (1975) FDA Project No. 2468, Food and Drug
Administration Contract No. 223-74-2104. Evaluation of test
compound locust bean gum, FDA 71-14
LRSO/FASEB (1972) Evaluation of the health aspects of carob bean gum
as a food - SCOGS-3. Prepared for Bureau of Foods, US Food and
Drug Administration Contract No. FDA 72-85
Maxwell, W. A. & Newell, G. W. (1972) Study of the mutagenic effects
of FDA-71-14 (locust bean gum). Unpublished report from the
Stanford Research Institute, submitted to the World Health
Organization by Hercules BV
Morgareidge, K. (1972) Teratological evaluation of FDA-71-14 (locust
bean gum). Unpublished report from the Food & Drug Research
Laboratories, Inc., submitted to the World Health Organization by
Hercules BV
Naber, E. C. & Smothers, S. E. (1975) Patterns of toxicity and
teratogenicity in the chick embryo resulting from the
administration of certain nutrients and food additives, Poultry
Sci., 54 (5), 1806
National Toxicology Program (1980) Carcinogenesis bioassay of locust
bean gum. DHHS publication No. (NIH) 81-1777
Rivier, C. (1952) Recherches sur le mode d'action du Nestargel,
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Robaislek, E. (1974) Bioavailable calorie assay of guar gum.
Unpublished report from WARF Institute, Inc., submitted to the
World Health Organization by the Institut Européen des Industries
de la Gomme de Caroube
Semenza, G. (1975) Report on the possible digestion of locust bean gum
in the stomach and/or in the small intestine in an in vitro
study. Unpublished report from the Eidgenossische Technische
Hochschule Zurich, submitted to the World Health Organization by
the Institut Européen des Industries de la Gomme de Caroube
Til, H. P., Spanjers, M. Th. & de Groot, A. P. (1974) Sub-chronic
toxicity study with locust bean gum in rats. Unpublished report
from Centraal Instituut voor Voedingsonderzoek TNO, submitted to
the World Health Organization by Hercules BV and the Institut
Européen des Industries de la Gomme de Caroube
Towle, G. A. & Schranz, R. E. (1975) The action of rat microflora on
carob bean gum solutions in vitro. Unpublished report from the
Hercules Research Center, submitted to the World Health
Organization by Hercules Incorporated
Tsay, L. B. & Whistler, R. L. (1975) Digestibility of galactomannans.
Unpublished report submitted to the World Health Organization by
Professor H. Neukom, Chairman of the Technical Committee of the
Institut Européen des Industries de la Gomme de Caroube
Vohra, P. & Kratzer, F. H. (1964) Growth inhibitory effects of certain
polysaccharides for chickens, Poultry Sci., 43, 1164-1170
Vohra, P., Shariff, G. & Kratzer, F. H. (1979) Growth inhibitory
effect of some gums and pectin for Tribolium castaneum larvae,
chickens and Japanese quail, Nutr. Rep. Internat'l, 19 (4),
463-469
See Also:
Toxicological Abbreviations