INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
WORLD HEALTH ORGANIZATION
TOXICOLOGICAL EVALUATION OF SOME
FOOD COLOURS, ENZYMES, FLAVOUR
ENHANCERS, THICKENING AGENTS, AND
CERTAIN FOOD ADDITIVES
WHO FOOD ADDITIVES SERIES 6
The evaluations contained in this publication were prepared by the
Joint FAO/WHO Expert Committee on Food Additives which met in Rome,
4-13 June 19741
World Health Organization Geneva 1975
1 Eighteenth Report of the Joint FAO/WHO Expert Committee on
Food Additives, Wld Hlth Org. techn. Rep. Ser., 1974, No. 557.
FAO Nutrition Meetings Report Series, 1974, No. 54.
XANTHAM GUM
BIOLOGICAL DATA
BIOCHEMICAL ASPECTS
The caloric availability and digestibility indicated that xantham
gum is not utilized by the body and the conclusion was substantiated
by finding that practically all of the gum fed during a seven-day
period could be accounted for in the faeces (Booth et al., 1963).
When 14C-labelled xantham gum prepared by fermentation of
uniformly labelled glucose with xanthomonas campestris was fed to rats
at a level of 2% (50 mg in total) in the diet a maximum of 15% of the
label was metabolized to carbon dioxide in 100 hours. In vitro tests
showed that the acetate content was labile at gastric pH. Acetate and
pyruvate accounted for only 9.8% of the label in the gum used. The
finding that 15% of the label was metabolized to carbon dioxide
indicated that the hexoses were used to a certain extent also. No
accumulation in tissues were found and the observed metabolism of
labelled material and distribution of 14C in tissues was that
expected from feeding a simple 14C-labelled molecule such as acetate
or a hexose. Analysis of faecal material showed no accumulation of the
five polysaccharide constituents, except acetate. Some 98% of the
radioactivity in the faeces could be attributed to unchanged or only
slightly modified polysaccharide. In vitro tests indicated that
nonenzymatic hydrolysis and the action of faecal-microorganisms is
responsible for the initial breakdown of polysaccharide in vivo
(Gumbmann, sine data).
TOXICOLOGICAL STUDIES
Special studies on reproduction
Rat
A three-generation reproduction study was carried out using
groups of 10 male and 20 female rats in the first generation and
20 male and 20 female rats in subsequent generations. Dosage levels
of 0, 0.25 and 0.5 g/kg/day were administered in the diet. Criteria
evaluated were survival, body weights, general appearance, behaviour,
the number of litters produced, numbers of live births and
stillbirths, physical condition of young, weight of young at birth and
weaning and the survival of young. Females that had fewer than two
litters were examined to determine whether there was foetal
resorption. Malformations in offspring were recorded and gross and
micropathological examinations made on the offspring of the second and
third generations. No adverse effects attributable to xantham gum were
found in this study (Woodard et al., 1973).
Acute toxicity
Animal Route LD50 References
(mg/kg bw)
Mouse oral > 1 000 Booth et al., 1963
i.p. > 50 Booth et al., 1963
i.v. 100-250 Hendrickson & Booth (sine data)
Rat oral >45 000 Jackson et al., (sine data I)
Dog oral >20 000 Jackson et al., (sine data II)
Daily application of a 1% solution for 15 days to rat skin
produced no signs of irritation. Daily application of a 1% solution
for five days to rabbit conjunctiva produced no signs of irritation.
Intradermal challenge tests in guinea-pigs did not produce evidence of
sensitization (Hendrickson & Booth (sine data)).
Short-term studies
Rat
A study was carried out on an unspecified number of rats fed on
diets containing 7.5% or 10% xantha gum for 99-110 days. No untoward
effects were observed in extensive investigations on these animals
(Booth et al., 1963).
In a 91-day feeding study a reduced rate of weight gain was found
in groups of rats receiving 7.5% or 15% of xantham gum in the diet.
Diets containing 3% or 6% gum did not reduce weight gain. No
significant alterations in haemoglobin, red and white cell counts, and
organ weights were observed in these rats. Histological examination of
tissues from rats at the 15% level showed no pathological effects. At
the highest dosage level the animals produced abnormally large faecal
pellets but diarrhoea did not occur. A paired-feeding test was used to
compare the growth of rats ingesting a diet containing 7.5% xantham
gum and comparable rats restricted to the same intake of control diet.
No difference in weight gains was found at the end of 18 days,
indicating the absence of a growth-inhibiting factor (Booth et al.,
1963).
Dog
Four groups of two male and two female young adult beagle dogs
were fed for two weeks on diets providing 0, 1 or 2 g/kg bw/day of
xantham gum or 2 g/kg/day of cellulose powder. Persistent diarrhoea
occurred in dogs receiving the 2 g/kg/day xantham gum and occasional
diarrhoea in those receiving 1 g/kg/day. All dogs, including controls,
lost weight but the weight loss was most marked in animals receiving
xantham gum. The red blood cell count, haemoglobin concentration and
serum cholesterol were lowered and the relative adrenal weight
increased in dogs receiving 2 g/kg/day xantham gum. These effects were
considered to be due to the persistent diarrhoea in this group. Liver
and kidney function tests indicated no disturbance in the function of
these organs. Extensive gross and histopathological examination failed
to detect lesions which could be attributed to ingestion of the gum
(Robbins et al., 1964).
Groups of three male and three female beagle dogs were fed on
diets supplying 0, 0.25 and 0.5 g/kg bw/day of xantham gum for 12
weeks. Animals receiving the 0.5 g/kg level had softer stools than
normal but no diarrhoea. Growth was slightly retarded in the males and
the serum cholesterol level was lowered in both sexes of the group
receiving 0.5 g/kg/day. No other untoward effects were seen. The no-
untoward-effect-level in this test was considered to be 0.25 g/kg/day
(Research report, 1964).
Xantham gum was administered in the diet at levels supplying 0,
0.25, 0.37 and 1.0 g/kg bw/day to groups of four male and four female
beagle dogs for 107 weeks. No effects attributable to administration
of gum were seen in the treated animals with regard to survival, food
intake, body weight gain, ECG, blood pressure, heart rate, body
temperature, and ophthalmic and neurological examinations. The
haemoglobin, total and differential white cell counts, coagulation and
prothrombin times, thrombocyte counts, serum alkaline phosphates,
blood urea nitrogen, blood glucose, SGOT and SPGT were the same in
control and treated animals. Urine pH, glucose and sediment contents
were comparable with controls but there was a dose related increase in
urine SG and a more frequent appearance of urinary albumin in dogs
consuming 1.0 g/kg/day of gum. Stool consistency was normal at the
0.37 g/kg level but loose at the top dosage level. The weight of
faeces showed a dose-related increase, as would be expected from
feeding a non-absorbed hydrophilic gum at high dosage levels. The
increased urinary SG is consistent with physiological adjustment for
the extra water excreted in the faeces. Examination of the appearance
and weights of organs and histopathological examinations failed to
detect any untoward effects of treatment with xantham gum at any
dosage level (Woodard et al., 1973).
Long-term studies
Rat
Groups of 30 male and 30 female rats were fed on diets for 104
weeks supplying 0, 0.25, 0.5 or 1.0 g/kg bw/day of xantham gum. No
abnormalities which could be attributed to ingestion of these
experimental diets were found with regard to survival, body weight
gain, food consumption, behaviour and appearance. Ophthalmic and
haematologic examination yielded normal results. Analysis of blood for
glucose, SGOT and prothrombin time showed no abnormalities in test
groups. Organ weights were within normal limits and no lesions
attributable to xantham gum were found on gross and histopathological
examination (Woodard, 1973).
Comments:
Studies indicate that this polymeric material is poorly absorbed.
It is partially degraded at gastric pH and probably also by intestinal
organisms in the rat. Molecules, or parts of the molecule which are
absorbed, are metabolized by normal energy-forming pathways. There is
no evidence of accumulation of the substance in tissues. At high
dosage levels it causes diarrhoea in dogs which was considered not
unusual for a hydrophilic gum. The possibility of this effect
occurring in man has been considered but use as food additive
according to general principles should preclude this. An adequate two-
year test in rats failed to show any carcinogenicity attributable to
the material. The reproduction study on rats revealed no untoward
effects.
EVALUATION
Level causing no toxicological effect
Rat: 1000 mg/kg bw
Estimate of acceptable daily intake for man
0-10 mg/kg bw
REFERENCES
Booth, A. N., Hendrickson, A. P. & DeEds, F. (1963) Toxicol. appl.
Pharmacol., 5, 478
Gumbmann, M. R., Research Report "Metabolism of 14C Polysaccharide
B-1459 by the Rat", Western Regional Research Laboratory, Albany,
California
Hendrickson, A. P. & Booth, A. N., Research Report "Supplementary
acute toxicological studies of polysaccharide B-1459", Western
Regional Research Laboratory, Albany, California
Jackson, N. N., Woodard, M. W. & Woodard, G., Research Report "Xantham
gum, acute oral toxicity to rats", Woodard Research Corporation
Jackson, N. N., Woodard, M. W. & Woodard, G., Research Report "Xanthan
gum, acute oral toxicity to dogs", Woodard Research Corporation
Research Report (1964) "Safety evaluation of polysaccharide B-1459
(xanthan gum) in laboratory animals - effects of feeding to dogs"
Western Regional Research Laboratory, Albany, California
Robbins, D. J., Moulton, J. E. & Booth, A. N. (1964) Food. Cosmet.
Toxicol., 2, 545
Technical bulletin on Keltral, Kelco Co., San Diego, California,
United States of America
Woodard, G. et al. (1973) Toxicol. appl., Pharmacol., 24, 30