TRAGACANTH GUM
EXPLANATION
The Joint FAO/WHO Expert Committee on Food Additives has reviewed
this substance many times in the past (Annex 1, references 19, 32, 44,
53, & 62). Toxicological monographs were prepared twice previously
(Annex 1, references 20 & 33).
Since the previous evaluation, additional data have become
available and are summarized and discussed here. Material from the
earlier monographs is incorporated into this evaluation.
BIOLOGICAL DATA
Biochemical aspects
In a comparative study of the hypocholesterolemic activity of
various mucilaginous polysaccharides, tragacanth gum fed at a level of
3% along with 3% cholesterol in the diet of cockerels inhibited the
development of hypercholesterolemia (Riccardi & Fahrenback, 1965).
Tragacanth gum administered i.p., s.c., or per os 24 hours before
hexobarbital had no effect on the hexobarbital sleeping time of mice.
The effect of phenobarbital and urethan pretreatment to induce a
shortening of hexobarbital sleeping time was blocked by i.p. injection
of tragacanth gum, thus suggesting the presence of a hepatic effect of
tragacanth gum (Fujimoto, 1965).
The influence of a number of hydrocolloids on the transit time of
digesta, stool weight, and colour of stools was investigated in rats.
Groups of 23 male rats were fed for 2 weeks the basal diet mixed
with 2 or 20% of a thickening agent added at the expense of the
entire diet. Tragacanth gum accelerated the digesta passage. All
hydrocolloids tested gave the stools a lighter colour and increased
their size and water content (Gohl & Gohl, 1977).
Ten Bacteroides species and several strains of anaerobic
bacteria found in the human colon were surveyed for their ability to
ferment 21 different complex polysaccharides. Many of the
Bacteroides strains and a strain of Bifidobacterium (B. longum)
fermented tragacanth gum (Salyers et al., 1977a & 1977b).
Fermentation of 20 polysaccharides by species of the family
Enterobacteriaceae were examined. Species of Klebsiella,
Serratia, and Yersinia fermented tragacanth gum. As a food
additive, tragacanth gum may lose some of its properties when exposed
in various ways to enteric organisms (Ochuba & von Riesen, 1980).
Female rats were dosed twice-daily with aqueous solutions of
tragacanth gum at doses of 20, 40, and 80 mg/kg b.w. over a period of
4 weeks. All doses caused uncoupling of oxidative phosphorylation in
liver and heart mitochondria and partial inhibition of mixed function
oxidases of liver endoplasmic reticulum. The uncoupling was reversible
in the case of heart mitochondria while it was progressive in liver
mitochondria. Tragacanth gum did not have any adverse effect on the
hepatic mixed-function oxidases at the 2 lower doses, while a 20%
inhibition developed after 30 doses with 2 × 40 mg/kg (Bachmann
et al., 1978).
Male albino Wistar rats were fed diets containing 0, 0.5, 1.5,
2.5, and 3.5 (w/w) tragacanth gum for 91 days. Microsomal protein and
PL-480 content of the liver were measured. No compound-related effects
were observed. Electron microscopy of liver and heart muscle from the
treated rats showed no abnormalities in any of the test animals
(Anderson et al., 1984).
Toxicological studies
Special studies on mutagenicity
Tragacanth gum was evaluated for genetic activity in the
following in vitro microbial assays, with and without activation:
Salmonella typhimurium (strains TA1535, TA1537, TA1538, TA98, and
TA100) and Saccharomyces cerevisiae strain D4. No mutagenic
activity was observed in any of these assays (Litton Bionetics, 1977).
Tragacanth gum was not mutagenic in a number of tests using
mammalian systems. These included: (a) Host Mediated Assay in vivo
in rats and mice using Salmonella typhimurium strain TA1530 and G46
or mitotic recombination frequency in S. cerevisiae D3, (b) a
cytogenic study in vivo of rat bone-marrow cells, and (c) an
in vitro study with human lung cells (wt. 38) in tissue culture
(Litton Bionetics, 1972).
Special studies on teratogenicity
I.p. injection of 1 ml 1% aqueous mucilage of Persian tragacanth
gum (single dose or 5 doses of 0.2 ml each) into mice between days 11
and 15 of gestation caused the death of all foetuses. Oral or s.c.
administration had no effect. All samples were found to be
contaminated with Enterobacter spp. and the embryotoxic effects were
attributed to bacterial metabolites (Frohberg et al., 1969).
Tragacanth gum showed no evidence of maternal toxicity or
teratogenicity after oral administration (as a suspension in corn oil)
at levels up to 1200 mg/kg b.w./day to pregnant mice (days 6-16 of
gestation) or to pregnant hamsters at dose levels up to 900 mg/kg
b.w./day (days 6-10 of gestation). Similar studies with pregnant rats
at dose levels up to 1200 mg/kg b.w. (days 6-15 of gestation) and with
pregnant rabbits at dose levels up to 700 mg/kg b.w. (days 6-18 of
gestation) resulted in significant maternal mortality in rats at the
1200 mg/kg b.w. dose level and in rabbits at dose levels of 150 and
700 mg/kg b.w. At autopsy, the gross pathological finding was marked
haemorrhage in the mucosa of the small intestine. Offspring from
animals surviving in the high-dose group as well as those in other
test groups showed no compound-related abnormalities in the soft or
skeletal tissues (FDRL, 1972).
A study was done using a chick embryo test system. Tragacanth
gum dissolved in 0.12 N HCl was injected either into the air sac or
the yolk of fertile chicken eggs at dose levels up to 7 mg/kg. The
administration of tragacanth gum did not result in a significant
increase in mortality. All hatched chicks appeared normal.
Abnormalities observed in eggs that failed to hatch were 22% test, 14%
solvent-control, and 3.41% flock background (Bodder, 1974).
Special studies on sensitization
Although there are only a few reports on sensitization to
tragacanth gum, the available information indicates that tragacanth
gum is a powerful allergen capable of causing extremely severe
reactions. Allergic reactions may occur as a result of inhalation or
oral ingestion (Gelfand, 1943; 1949).
The immunogenicity of tragacanth gum was demonstrated in an
in vivo test using a foot pad swelling test in mice. Purification of
the gum led to a marked reduction of the immune response (Strobel
et al., 1982).
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 sodium
carboxymethyl cellulose) were studied. Each gum was administered by
gavage to 5 groups of 10 animals, with 5 males and 5 females in each
group. Vehicles utilized were water, mineral oil, corn oil, and
soybean oil. The animals were fasted 18 hours prier to dosing with
food and water available ad libitum during the 14-day observation
period. LD50 values observed ranged from 2.6 to 18.0 g/kg, with most
values in the 5 to 10 g/kg range. Generally, the rabbit was the most
sensitive species and the rat and mouse the least sensitive (Bailey,
personal communication to WHO, 1976).
Short-term studies
Rats
Groups of newly-weaned rats (10 per group) were fed a soybean-
corn meal diet containing 2% tragacanth gum for 37 days. Tragacanth
gum had no effect on the digestibility of the diet, nor was there any
significant effect on growth (Vohra et al., 1979).
Tragacanth gum was used in a 6-7 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 growth rates due to lower energy intakes. None of
the polysaccharides fed, however, decreased energy utilization.
Similarly, all polysaccharides increased small intestine weights by up
to about 30% without grossly altering mucosal protein or DNA per unit
of length. Concerning the effect on the large intestine, tragacanth
gum had a pronounced effect on caecum weight, which increased by
factors of 1.8, 2.0, and 4.2 for additions of 10, 20, and 40%,
respectively. The degree of the observed changes was determined mainly
by the dietary concentration of the polysaccharide and its
accessibility to bacterial degradation within the intestinal tract
(Elsenhaus et al., 1981).
Groups of 50 male and 50 female Osborne-Mendel rats
(approximately 21 days of age) were maintained on diets containing 0,
0.006, 0.06, 0.6, or 6.0% ppm tragacanth gum. After 13 weeks on the
test diets, the rats were bred to produce an F1 generation. The
offspring were weaned at day 21 and placed on their respective diets.
The animals in the F0 generation were maintained on the test diets
for a total period of 27 weeks. Groups of 50 male and 50 female rats
of the F1 generation were maintained on the test diets for
approximately 20 weeks. During the course of the study, body weights
and food intake were measured. Reproduction data included the
fertility index, total number of progeny, average litter size of
pregnant females, total number of liveborn, viability index, survivors
to days 4 and 21, weaning index at birth, and weaning weights. At
termination of the study, haematological and clinical chemistry
studies were carried out. Organ weights were determined, and a
complete histological study was made of the principal tissues and
organs. Special studies were carried out on liver composition (DNA,
RNA, and protein levels), liver DNA synthesis, and intermediary
metabolism.
Both males and females in the 6% group showed significantly lower
body weights, as well as decreased food efficiency, than the controls.
Lower body weights were also observed in the F1 generation,
particularly in the males. Haematological measurements showed no
compound-related effects. Only minor effects were noted in the various
clinical chemistry parameters. Reproduction data were comparable for
test and control animals. Histological studies did not show any
compound-related effects. Enlarged livers were noted in the 6% group,
but the enlargement was not associated with any significant change in
liver composition or with histological changes. The ATP/ADP ratio in
liver preparations for F0 animals was markedly decreased, but this
effect was not observed in F1 animals (Graham et al., 1985).
Chickens
Groups of day-old broiler chickens (7 per group) were fed a
soybean-corn diet containing 2% tragacanth gum for 24 days. The
dietary intake of 10 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. Body weights and the
digestibility of the diet were reduced significantly by the inclusion
of tragacanth gum in the diet (Vohra et al., 1979).
Quail
Groups of day-old Japanese quail (10 per group) were fed a
soybean-corn diet containing 2% tragacanth gum for 36 days. Tragacanth
gum did not affect significantly the growth of the quail or the
digestibility of the diet (Vohra et al., 1979).
Long-term studies
No information available.
Observations in man
Following a 7-day control period, 5 healthy men ingested 9.9 g
tragacanth gum daily (3 × 3.3 g-portion gelled in 200 ml water) for 32
days. The following measurements were made during the control period
and at the end of the test period: blood glucose, insulin, serum lipid
estimations of cholesterol and HDL cholesterol, phospholipids,
triglycerides, haematological indices, and biochemical analyses.
Twenty-four-hour urine samples were collected and tested for sugar,
protein, and blood. Five-day faecal collections were made during days
2-6 of the control period and during days 16-20 of the treatment
period. The tragacanth gum was well-tolerated and no adverse effects
were reported in any of the volunteers. Tragacanth gum had no
significant effect on any of the parameters measured with the
exception that intestinal transit time decreased, and faecal wet- and
dry-weights were increased in all subjects at the end of the test
period. Four subjects also showed an increase in faecal fat
concentration (Eastwood, et al., 1984).
Comments
Tragacanth gum is fermented by several strains of bacteria found
in the human colon.
An earlier study showed changes in liver microsomal enzyme
activity and in the oxidative phosphorylation function of heart and
liver mitochondria isolated from rats fed tragacanth gum. However, a
recent study showed no detectable ultrastructural abnormalities in rat
heart or liver and no changes in microsomal protein or P-450 content
of the liver that could be attributable to tragacanth gum.
Tragacanth gum was not mutagenic in bacterial or mammalian
systems. No teratogenic effects were observed in studies in mice,
rats, guinea-pigs, or rabbits. Maternal toxicity observed in rats and
rabbits, at the highest levels tested, may have been due to the mode
of administration (suspended in corn oil), rather than to any innate
toxicity of the gum.
Tragacanth gum fed to rats at dietary levels up to 6% had no
effect on reproductive performance nor on post-partum development of
the pups. The only effects observed in both the F0 and F1
generations were lower body weights and decreased feed-efficiency at
the 6% level. Since these effects were not accompanied by any
compound-related histological changes in any tissues or organs, the
effects may be due to the bulking effect of this non-nutritive
substance, rather than any innate toxicity. The highest level tested
in this study exceeds the maximum level (5%) recommended for non-
nutrients.
Relatively high levels of tragacanth gum were well-tolerated by
man. However, possible allergic effects need to be considered.
EVALUATION
Level causing no toxicological effect
Rat: 6000 ppm tragacanth gum in the diet, equivalent to
3000 mg/kg b.w./day.
Estimate of acceptable daily intake for man
ADI "not specified".
REFERENCES
Anderson, D.M.W., Ashby, P., Busuttil, A., Kempson, S.A., & Lawson,
M.E. (1984). Transmission electron microscopy of heart and liver
tissues from rats fed with gums arabic and tragacanth.
Toxicology Letters, 21, 83-89.
Bachmann, E., Weber, E., Post, M., & Zbinden, G. (1978). Biochemical
effects of gum arabic, gum tragacanth and carboxymethyl cellulose
in rat heart and liver. Pharmacology, 17, 39-49.
Bodder, R. (1974). Evaluation of chemicals for toxic and teratogenic
effects using the chick embryo as a test system. Unpublished
report of Warf Institute, Inc. Submitted to WHO by U.S. Food and
Drug Administration.
Eastwood, M.A., Brydon, W.G., & Anderson, D.M.W. (1984). The effects
of dietary gum tragacanth in man. Toxicology Letters, 21,
73-81.
Elsenhaus, B., Blume, R., & Caspary, W.F. (1981). Long-term feeding
of unavailable carboydrate gelling agents. Influence of dietary
concentration and microbiological degradation on adaptive
responses in the rat. Am. J. Clin. Nutr., 34, 1837-48.
FDRL, 1972. Teratology evaluation of gum tragacanth in mice, rats,
hamsters and rabbits. Unpublished report of Food and Drug
Research Laboratories, Inc. Submitted to WHO by U.S. Food and
Drug Administration.
Frohberg, H., Oettel, H., & Zeller, H. (1969). Concerning the
mechanisms of the fetal toxic effects of tragacanth. Arch.
Toxicol., 25, 268-295.
Fujimoto, J.M. (1965). Effect of gum tragacanth, urethan, and
phenobarbital on hexobarbital narcosis in mice. Toxicol. Appl.
Pharmacol., 7, 287-290.
Gelfand, H.H. (1943). The allergenicity of vegetable gums, a case of
asthma due to tragacanth. J. Allergy, 14, 203.
Gelfand, H.H. (1949). Vegetable gums by ingestion in etiology of
allergic disorders. J. Allergy, 20, 311-321.
Graham, S.L., Friedman, L., & Garthoff, L. (1985). The subchronic
effects of gum tragacanth on F0 and F1 generation Osborn-Mendel
rats. Unpublished report of the Food and Drug Administration.
Submitted to WHO by U.S. Food and Drug Administration.
Gohl, B. & Gohl, I. (1977). The effect of viscous substances on the
transit time of barley digesta in rats. J. Sci. Fd. Agric.,
28, 911-915.
Litton Bionetics (1972). Summary of mutagenicity screening studies,
contract FDA71-268, gum tragacanth host-mediated assay,
cytogenetics, dominant lethal assay, L.B.I. Project No. 2311.
Unpublished report of Litton Bionetics Inc. Submitted to WHO by
U.S. Food and Drug Administration.
Litton Bionetics (1977). Mutagenicity evaluation of gum tragacanth,
LBI Project No. 20671. Unpublished report of Litton Bionetics
Inc. Submitted to WHO by U.S. Food and Drug Administration.
Ochuba, G.U. & von Riesen, V.L. (1980). Fermentation of
polysaccharides by Klebsiellae and other facultative bacilli.
Appl. Environ. Microbiol., 39, 988-992.
Riccardi, B.A. & Fahrenbach, M.J. (1965). Hypocholestrolemic activity
of mucilaginous polysaccharides in white leghorn cockerels.
Fed. Proc., 24, 263-265.
Salyers, A.A., Vercellotti, J.R., West, S.E.H., & Wilkins, T.D.
(1977a). Fermentation of mucins and plant polysaccharides by
strains of Bacteroides from the human colon. Appl. Environ.
Microbiol., 33, 319-322.
Salyers, A.A., Vercellotti, J.R., West, S.E.H., & Wilkins, T.D.
(1977b). Fermentation of mucins and plant polysaccharides by
anaerobic bacteria from the human colon. Appl. Environ.
Microbiol., 34, 529-533.
Strobel, S., Ferguson, A., & Anderson, D.M.W. (1982). Immunogenicity
of food and food additives - In vivo testing of gums arabic,
karaya and tragacanth. Toxicology Letters, 14, 247-252.
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. Int., 19, 463-469.
ANNEX 1
REPORTS AND OTHER DOCUMENTS RESULTING FROM MEETINGS OF THE JOINT
FAO/WHO EXPERT COMMITTEE ON FOOD ADDITIVES
1. General principles governing the use of food additives (First
report of the Joint FAO/WHO Expert Committee on Food Additives).
FAO Nutrition Meetings Report Series, No. 15, 1958; WHO Technical
Report Series, No. 129, 1957 (out of print).
2. Procedures for the testing of intentional food additives to
establish their safety for use (Second report of the Joint
FAO/WHO Expert Committee on Food Additives). FAO Nutrition
Meetings Report Series, No. 17, 1958; WHO Technical Report
Series, No. 144, 1958 (out of print).
3. Specifications for identity and purity of food additives
(antimicrobial preservatives and antioxidants) (Third report of
the Joint FAO/WHO Expert Committee on Food Additives). These
specifications were subsequently revised and published as
Specifications for identity and purity of food additives, Vol. I.
Antimicrobial preservatives and antioxidants, Rome, Food and
Agriculture Organization of the United Nations, 1962 (out of
print).
4. Specifications for identity and purity of food additives (food
colours) (Fourth report of the Joint FAO/WHO Expert Committee on
Food Additives). These specifications were subsequently revised
and published as Specifications for identity and purity of food
additives, Vol. II. Food colours, Rome, Food and Agriculture
Organization of the United Nations, 1963 (out of print).
5. Evaluation of the carcinogenic hazards of food additives (Fifth
report of the Joint FAO/WHO Expert Committee on Food Additives).
FAO Nutrition Meetings Report Series, No. 29, 1961; WHO Technical
Report Series, No. 220, 1961 (out of print).
6. Evaluation of the toxicity of a number of antimicrobials and
antioxidants (Sixth report of the Joint FAO/WHO Expert Committee
on Food Additives). FAO Nutrition Meetings Report Series, No. 31,
1962; WHO Technical Report Series, No. 228, 1962 (out of print).
7. Specifications for the identity and purity of food additives and
their toxicological evaluation: emulsifiers, stabilizers,
bleaching and maturing agents (Seventh report of the Joint
FAO/WHO Expert Committee on Food Additives). FAO Nutrition
Meetings Report Series, no. 35, 1964; WHO Technical Report
Series, No. 281, 1964 (out of print).
8. Specifications for the identity and purity of food additives and
their toxicological evaluation; food colours and some
antimicrobials and antioxidants (Eighth report of the Joint
FAO/WHO Expert Committee on Food Additives). FAO Nutrition
Meetings Report Series, No. 38, 1965; WHO Technical Report
Series, No. 309, 1965 (out of print).
9. Specifications for identity and purity and toxicological
evaluation of some antimicrobials and antioxidants. FAO Nutrition
Meetings Report Series, No. 38A, 1965; WHO/Food/Add/24.65 (out of
print).
10. Specifications for identity and purity and toxicological
evaluation of food colours. FAO Nutrition Meetings Report Series,
No. 35B, 1966; WHO/Food Add/66.25.
11. Specifications for the identity and purity of food additives
and their toxicological evaluation: some antimicrobials,
antioxidants, emulsifiers, stabilizers, flour-treatment agents,
acids, and bases (Ninth report of the Joint FAO/WHO Expert
Committee on Food Additives). FAO Nutrition Meetings Report
Series, No. 40, 1966; WHO Technical Report Series, No. 339, 1966
(out of print).
12. Toxicological evaluation of some antimicrobials, antioxidants,
emulsifiers, stabilizers, flour-treatment agents, acids, and
bases. FAO Nutrition Meetings Report Series, No. 40A, B, C;
WHO/Food Add/67.29.
13. Specifications for the identity and purity of food additives and
their toxicological evaluation: some emulsifiers and stabilizers
and certain other substances (Tenth report of the Joint FAO/WHO
Expert Committee on Food Additives). FAO Nutrition Meetings
Report Series, No. 43, 1967; WHO Technical Report Series, No.
373, 1967.
14. Specifications for the identity and purity of food additives and
their toxicological evaluation: some flavouring substances and
non-nutritive sweetening agents (Eleventh report of the Joint
FAO/WHO Expert Committee on Food Additives). FAO Nutrition
Meetings Report Series, No. 44, 1968; WHO Technical Report
Series, No. 383, 1968.
15. Toxicological evaluation of some flavouring substances and non-
nutritive sweetening agents. FAO Nutrition Meetings Report
Series, No. 44A, 1968; WHO/Food Add/68.33.
16. Specifications and criteria for identity and purity of some
flavouring substances and non-nutritive sweetening agents. FAO
Nutrition Meetings Report Series, No. 44B, 1969; WHO/Food
Add/69.31.
17. Specifications for the identity and purity of food additives and
their toxicological evaluation; some antibiotics (Twelfth report
of the Joint FAO/WHO Expert Committee on Food Additives). FAO
Nutrition Meetings Report Series, No. 45, 1969; WHO Technical
Report Series, No. 430, 1969.
18. Specifications for the identity and purity of some antibiotics.
FAO Nutrition Meetings Report Series, No. 45A, 1969; WHO/Food
Add/69.34.
19. Specifications for the identity and purity of food additives and
their toxicological evaluation; some food colours, emulsifiers,
stabilizers, anticaking agents, and certain other substances
(Thirteenth report of the Joint FAO/WHO Expert Committee on Food
Additives). FAO Nutrition Meetings Report Series, No. 46, 1970;
WHO Technical Report Series, No. 445, 1970.
20. Toxicological evaluation of some food colours, emulsifiers,
stabilizers, anticaking agents, and certain other substances. FAO
Nutrition Meetings Report Series, No. 46A, 1970; WHO/Food
Add/70.36.
21. Specifications for the identity and purity of some food colours,
emulsifiers, stabilizers, anticaking agents, and certain other
food additives. FAO Nutrition Meetings Report Series, No. 46B,
1970; WHO/Food Add/70.37.
22. Evaluation of food additives; specifications for the identity and
purity of food additives and their toxicological evaluation; some
extraction solvents and certain other substances; and a review of
the technological efficacy of some antimicrobial agents
(Fourteenth report of the Joint FAO/WHO Expert Committee on Food
Additives). FAO Nutrition Meetings Report Series, No. 48, 1971;
WHO Technical Report Series, No. 462, 1971.
23. Toxicological evaluation of some extraction solvents and certain
other substances. FAO Nutrition Meetings Report Series, No. 48A,
1971; WHO/Food Add/70.39.
24. Specifications for the identity and purity of some extraction
solvents and certain other substances. FAO Nutrition Meetings
Report Series, No. 48B, 1971; WHO/Food Add/70.40.
25. A review of the technological efficacy of some antimicrobial
agents. FAO Nutrition Meetings Report Series, No. 48C, 1971;
WHO/Food Add/70.41.
26. Evaluation of food additives: some enzymes, modified starches,
and certain other substances: toxicological evaluations and
specifications and a review of the technological efficacy of some
antioxidants (Fifteenth report of the Joint FAO/WHO Expert
Committee on Food Additives). FAO Nutrition Meetings Report
Series, No. 50, 1972; WHO Technical Report Series, No. 488, 1972.
27. Toxicological evaluation of some enzymes, modified starches, and
certain other substances. FAO Nutrition Meetings Report Series,
No. 50A, 1972; WHO Food Additives Series, No. 1, 1972.
28. Specifications for the identity and purity of some enzymes and
certain other substances. FAO Nutrition Meetings Report Series,
No. 50B, 1972; WHO Food Additives Series, No. 2, 1972.
29. A review of the technological efficacy of some antioxidants and
synergists. FAO Nutrition Meetings Report Series, No. 50C, 1972;
WHO Food Additives Series, No. 3, 1972.
30. Evaluation of certain food additives and the contaminants
mercury, lead, and cadmium (Sixteenth report of the Joint FAO/WHO
Expert Committee on Food Additives). FAO Nutrition Meetings
Report Series, No. 51, 1972; WHO Technical Report Series, No.
505, 1972, and corrigendum.
31. Evaluation of mercury, lead, cadmium, and the food additives
amaranth, diethylpyrocarbamate, and octyl gallate. FAO Nutrition
Meetings Report Series, No. 51A, 1972; WHO Food Additives Series,
No. 4, 1972.
32. Toxicological evaluation of certain food additives with a review
of general principles and of specifications, (Seventeenth report
of the Joint FAO/WHO Expert Committee on Food Additives). FAO
Nutrition Meetings Report Series, No. 53, 1974; WHO Technical
Report Series, No. 539, 1974, and corrigendum (out of print).
33. Toxicological evaluation of certain food additives including
anticaking agents, antimicrobials, antioxidants, emulsifiers, and
thickening agents. FAO Nutrition Meetings Report Series, No. 53A,
1974; WHO Food Additives Series, No. 5, 1974.
34. Specifications for identity and purity of thickening agents,
anticaking agents, antimicrobials, antioxidants and emulsifiers.
FAO Food and Nutrition Paper, No. 4, 1978.
35. Evaluation of certain food additives (Eighteenth report of the
Joint FAO/WHO Expert Committee on Food Additives). FAO Nutrition
Meetings Report Series, No. 54, 1974; WHO Technical Report
Series, No. 557, 1974, and corrigendum.
36. Toxicological evaluation of some food colours, enzymes, flavour
enhancers, thickening agents, and certain other food additives.
FAO Nutrition Meetings Report Series, No. 54A, 1975; WHO Food
Additives Series, No. 6, 1975.
37. Specifications for the identity and purity of some food colours,
flavour enhancers, thickening agents, and certain food additives.
FAO Nutrition Meetings Report Series, No. 54B, 1975; WHO Food
Additives Series, No. 7, 1975.
38. Evaluation of certain food additives: some food colours,
thickening agents, smoke codensates, and certain other substances
(Nineteenth report of the Joint FAO/WHO Expert Committee on Food
Additives). FAO Nutrition Meetings Report Series, No. 55, 1975;
WHO Technical Report Series, No. 576, 1975.
39. Toxicological evaluation of some food colours, thickening agents,
and certain other substances. FAO Nutrition Meetings Report
Series, No. 55A, 1975; WHO Food Additives Series, No. 8, 1975.
40. Specifications for the identity and purity of certain food
additives. FAO Nutrition Meetings Report Series, No. 55B, 1976;
WHO Food Additives Series, No. 9, 1976.
41. Evaluation of certain food additives (Twentieth report of the
Joint FAO/WHO Expert Committee on Food Additives). FAO Food and
Nutrition Series, No. 1. 1976; WHO Technical Report Series, No.
599, 1976.
42. Toxicological evaluation of certain food additives. WHO Food
Additives Series, No. 10, 1976.
43. Specifications for the identity and purity of some food
additives. FAO Food and Nutrition Series, No. 1B, 1977; WHO Food
Additives Series, No. 11, 1977.
44. Evaluation of certain food additives (Twenty-first report of the
Joint FAO/WHO Expert Committee on Food Additives). WHO Technical
Report Series, No. 617, 1978.
45. Summary of toxicological data of certain food additives. WHO Food
Additives Series, No. 12, 1977.
46. Specifications for identity and purity of some food additives,
including antioxidants, food colours, thickeners, and others. FAO
Nutrition Meetings Report Series, No. 57, 1977.
47. Evaluation of certain food additives and contaminants (Twenty-
second report of the Joint FAO/WHO Expert Committee on Food
Additives). WHO Technical Report Series, No. 631, 1978.
48. Summary of toxicological data of certain food additives and
contaminants. WHO Food Additives Series, No. 13, 1978.
49. Specifications for the identity and purity of certain food
additives. FAO Food and Nutrition Paper, No. 7, 1978.
50. Evaluation of certain food additives (Twenty-third report of the
Joint FAO/WHO Expert Committee on Food Additives). WHO Technical
Report Series, No. 648, 1980, and corrigenda.
51. Toxicological evaluation of certain food additives. WHO Food
Additives Series, No. 14, 1980.
52. Specifications for identity and purity of food colours,
flavouring agents, and other food additives. FAO Food and
Nutrition Paper, No. 12, 1979.
53. Evaluation of certain food additives (Twenty-fourth report of the
Joint FAO/WHO Expert Committee on Food Additives). WHO Technical
Report Series, No. 653, 1980.
54. Toxicological evaluation of certain food additives. WHO Food
Additives Series, No. 15, 1980.
55. Specifications for identity and purity of food additives
(sweetening agents, emulsifying agents, and other food
additives). FAO Food and Nutrition Paper, No. 17, 1980.
56. Evaluation of certain food additives (Twenty-fifth report of the
Joint FAO/WHO Expert Committee on Food Additives). WHO Technical
Report Series, No. 669, 1981.
57. Toxicological evaluation of certain food additives. WHO Food
Additives Series, No. 16, 1981.
58. Specifications for identity and purity of food additives (carrier
solvents, emulsifiers and stabilizers, enzyme preparations,
flavouring agents, food colours, sweetening agents, and other
food additives). FAO Food and Nutrition Paper, No. 19, 1981.
59. Evaluation of certain food additives and contaminants (Twenty-
sixth report of the Joint FAO/WHO Expert Committee on Food
Additives). WHO Technical Report Series, No. 683, 1982.
60. Toxicological evaluation of certain food additives. WHO Food
Additives Series, No. 17, 1982.
61. Specifications for the identity and purity of certain food
additives. FAO Food and Nutrition paper, No. 25, 1982.
62. Evaluation of certain food additives and contaminants (Twenty-
seventh report of the Joint FAO/WHO Expert Committee on Food
Additives). WHO Technical Report Series, No. 696, 1983, and
corrigenda.
63. Toxicological evaluation of certain food additives and
contaminants. WHO Food Additives Series, no. 18, 1983.
64. Specifications for the identity and purity of certain food
additives. FAO Food and Nutrition Paper, No. 28, 1983.
65. Guide to specifications - General notices, general methods,
identification tests, test solutions, and other reference
materials. FAO Food and Nutrition Paper, No. 5, Rev. 1, 1983.
66. Evaluation of certain food additives and contaminants (Twenty-
eighth report of the Joint FAO/WHO Expert Committee on Food
Additives). WHO Technical Report Series, No. 710, 1984.
67. Toxicological evaluation of certain food additives and
contaminants. WHO Food Additives Series, No. 19, 1984.
68. Specifications for the identity and purity of certain food
additives. FAO Food and Nutrition paper, No. 31/1, 1984.
69. Specifications for the identity and purity of certain food
additives. FAO Food and Nutrition Paper, No. 31/2, 1984.
70. Evaluation of certain food additives and contaminants (Twenty-
ninth report of the Joint FAO/WHO Expert Committee on Food
Additives). WHO Technical Report Series, No. 733, 1986.
ANNEX 2
ABBREVIATIONS USED IN THE MONOGRAPHS
ADI acceptable daily intake
BUN blood urea nitrogen
b.w. body weight
CD50 convulsive dose, median
CHO Chinese hampster ovary
DCI immobilized glucose isomerase from S. rubiginosis
FAO Food and Agriculture Organization of the United Nations
FFA free fatty acids
g gram
GOT see SGOT
GPM alpha-D-glucopyranosido-1,6-mannitol
GPS alpha-D-glucopyranosido-1,6-sorbitol
GPT see SGPT
Hb haemoglobin
HFE non-immobilized glucose isomerase from S. rubiginosis
HGS hydrogenated glucose syrups
IARC International Agency for Research on Cancer
i.m. intramuscular
i.p. intraperitoneal
IPCS International Programme on Chemical Safety
IRI immunoreactive insulin
i.v. intravenous
JECFA Joint FAO/WHO Expert Committee on Food Additives
kg kilogram
LD50 lethal dose, median
LDH lactate dehydrogenase
4-MEI 4-methylimidazole
µg microgram
µl microlitre
µM micromolar
mg milligram
ml millilitre
mM millimolar
MTD maximum tolerated dose
NAG N-acetylglucosaminidase
nM nanomolar
NOEL no observed effect level
OCT ornithine carbamoyl transferase
PCV haematocrit
per os by mouth
RBC red blood cell (erythrocyte count)
SAP serum alkaline phosphatase
s.c. subcutaneous
SG specific gravity
SGOT serum glutamate-oxaloacetate transaminase
SGPT serum glutamate-pyruvate transaminase
T3 triiodothyronine
T4 thyroxine
TG triglycerides
THI 2-acetyl-4(5)-tetrahydroxybutylimidazole
WBC white blood cell (total leukocyte count)
WHO World Health Organization
w/w weight/weight
ANNEX 3
JOINT FAO/WHO EXPERT COMMITTEE ON FOOD ADDITIVES
Geneva, 3-12 June 1985
Members invited by FAO
Dr I. Chakravarty, Professor and Head, Department of Biochemistry and
Nutrition, All India Institute of Hygiene and Public Health,
Calcutta, India
Dr W.H.B. Denner, Head, Food Composition and Information Unit, Food
Sciences Division, Ministry of Agriculture, Fisheries and Food,
London, England (Vice-Chairman)
Dr S.W. Gunner, Director General, Food Directorate, Health Protection
Branch, Health and Welfare Canada, Ottawa, Canada
Professor K. Kojima, College of Environmental Health, Azabu
University, Sagamihara-Shi, Kanagawa-Ken, Japan
Dr W. Kroenert, Head, Food Chemistry Division, Max von Pettenkofer
Institute, Federal Office of Public Health, Berlin (West)
Dr R. Mathews, Director, Food Chemicals Codex, National Academy of
Sciences, Washington, DC, USA
Dr J.P.M. Modderman, Food Additives Chemistry Evaluation Branch,
Center for Food Safety and Applied Nutrition, Food and Drug
Administration, Washington, DC, USA
Professor F.J. Pellerin, Faculty of Pharmacy, Université de Paris XI,
Centre hospitalier Corentin-Celton, Issy-les-Moulineaux, France
Members invited by WHO
Dr H. Blumenthal, Director, Division of Toxicology, Center for Food
Safety and Applied Nutrition, Food and Drug Administration,
Washington, DC, USA
Dr A.H. El-Sebae, Chairman, Pesticides Division, Faculty of
Agriculture, Alexandria University, Alexandria, Egypt
Professor P.E. Fournier, Professor of Clinical Toxicology, Hôpital
Fernand Widal, Paris, France
Dr B. MacGibbon, Senior Principal Medical Officer, Division of
Toxicology and Environmental Protection, Department of Health and
Social Security, London, England
Professor K.A. Odusote, Associate Professor of Medicine, College of
Medicine, University of Lagos, Lagos, Nigeria (Rapporteur)
Dr P. Pothisiri, Director, Food Control Division, Food and Drug
Administration, Ministry of Public Health, Bangkok, Thailand
Professor M.J. Rand, Head, Department of Pharmacology, University of
Melbourne, Victoria, Australia (Chairman)
*Dr V.A. Tutelyan, Deputy Director, Institute of Nutrition, Academy of
Medical Sciences of the USSR, Moscow, USSR
Secretariat
Dr J.R.P. Cabral, Scientist, Unit of Mechanisms of Carcinogenesis,
International Agency for Research on Cancer, Lyons, France
Mr A. Feberwee, Chairman, Codex Committee on Food Additives; and
Deputy Director, Nutrition and Quality Affairs, Ministry of
Agriculture and Fisheries, The Hague, The Netherlands (Member of
FAO Secretariat)
Professor C.L. Galli, Professor of Experimental Toxicology, Institute
of Pharmacology and Pharmacognosy, University of Milan, Milan,
Italy (WHO Temporary Adviser)
Dr W. Grunow, Head, Division of Food Toxicology, Max von Pettenkofer
Institute, Federal Office of Public Health, Berlin (West) (WHO
Temporary Adviser)
Mr R. Haigh, Principal Administrator, Commission of the European
Communities, Brussels, Belgium (WHO Temporary Adviser)
Dr Y. Hayashi, Director, Division of Pathology, Biological Safety
Research Centre, National Institute of Hygienic Sciences, Tokyo,
Japan (WHO Temporary Adviser)
Dr J.L. Herrman, Division of Food and Color Additives, Center for Food
Safety and Applied Nutrition, Food and Drug Administration,
Washington, DC, USA (WHO Consultant)
Dr F. Käferstein, Responsible Officer, Food Safety Programme, Division
of Environmental Health, WHO, Geneva, Switzerland
Dr N. Rao Maturu, Food Standards Officer, Joint FAO/WHO Food Standards
Programme, FAO, Rome, Italy
* Invited but unable to attend
Dr M. Mercier, Manager, International Programme on Chemical Safety,
Division of Environmental Health, WHO, Geneva, Switzerland
Dr A.W. Randell, Nutrition Officer (Food Science), Food Policy and
Nutrition Division, FAO, Rome, Italy (FAO Joint Secretary)
Dr S.I. Shibko, Associate Director for Regulatory Evaluation, Division
of Toxicology, Center for Food Safety and Applied Nutrition, Food
and Drug Administration, Washington, DC, USA (WHO Temporary
Adviser)
Dr P. Shubik, Senior Research Fellow, Green College, Oxford, England
(WHO Temporary Adviser)
Professor R. Truhaut, Professor Emeritus of Toxicology, Department of
Toxicology and Industrial Hygiene, René Descartes University,
Paris, France (WHO Temporary Adviser)
Dr G. Vettorazzi, Senior Toxicologist, International Programme on
Chemical Safety, Division of Environmental Health, WHO, Geneva,
Switzerland (WHO Joint Secretary)
Dr R. Walker, Department of Biochemistry, University of Surrey,
Guildford, Surrey, England (WHO Temporary Adviser)
ANNEX 4
ACCEPTABLE DAILY INTAKES, OTHER TOXICOLOGICAL RECOMMENDATIONS AND INFORMATION ON SPECIFICATIONS
ADI for man
Specifications1 and other
toxicological
recommendations
A. Specific food additives
Enzyme preparations and enzyme immobilizing agents
Carbohydrase (alpha-amylase) R ADI not specified2
from Bacillus licheniformis
Glucose isomerase (immobilized) S Acceptable3
from Actinoplanes missouriensis
Glucose isomerase S No ADI allocated4
from Bacillus coagulans
Glucose isomerase (immobilized) S Acceptable3
from Bacillus coagulans
Glucose isomerase (immobilized) S Acceptable3
from Streptomyces olivaceus
Glucose isomerase (immobilized) S Acceptable3
from Streptomyces olivochromogenes
Glucose isomerase R No ADI allocated4
from Streptomyces rubiginosus
Glucose isomerase (immobilized) R Acceptable3
from Streptomyces rubiginosus)
ANNEX 4 (Con't)
ADI for man
Specifications1 and other
toxicological
recommendations
Polyethylenimine - Suitable5
Flavouring agent
Benzyl acetate S 0-56 mg/kg b.w.
Flour treatment agent
Chlorine S 2.5 g Cl2/kg flour7
Food acids and their salts
Aluminium ammonium sulfate N 0-0.6 mg/kg b.w. 6,8
Aluminium, calcium, magnesium, O No ADI allocated9
potassium, and sodium salts
of capric, caprylic, lauric
and oleic acids
Ammonium succinate O No ADI allocated9
Calcium adipate O No ADI allocated9
Calcium aluminium silicate S ADI "not specified"2, 10
(previously aluminium
calcium silicate)
Calcium fumarate O No ADI allocated9
Calcium hydrogen carbonate O No ADI allocated9
Calcium succinate O No ADI allocated9
Dipotassium guanylate N ADI "not specified"2, 12
Dipotassium inosinate N ADI "not specified"2, 13
Ferric ammonium citrate S 0-0.8 mg/kg b.w.11
Guanylic acid N ADI "not specified"2, 12
Inosinic acid N ADI "not specified"2, 13
ANNEX 4 (Con't)
ADI for man
Specifications1 and other
toxicological
recommendations
Magnesium acetate O No ADI allocated9
Magnesium adipate O No ADI allocated9
Magnesium citrate O No ADI allocated9
Magnesium succinate O No ADI allocated9
Monomagnesium phosphate O No ADI allocated9
Potassium aluminosilicate O No ADI allocated9
Potassium fumarate O No ADI allocated9
Potassium succinate O No ADI allocated9
Potassium sulfate N ADI "not specified"2
Potassium sulfite N 0-0.7 mg/kg b.w.14
Sodium aluminium polyphosphate O No ADI allocated9
Sodium sorbate O 0-25 mg/kg b.w.15
Food colours
Brown FK N 0-0.075 mg/kg b.w.6
Caramel colours
Class I R,T ADI "not specified"2
Class II N,T No ADI allocated16
Class III R,T 0-200 mg/kg b.w.
(0-150 mg/kg b.w.
on solids basis)
ANNEX 4 (Con't)
ADI for man
Specifications1 and other
toxicological
recommendations
Caramel colours (con't)
Class IV R,T 0-200 mg/kg b.w.
(0-150 mg/kg b.w.
on solids basis)
Carthamus yellow R,T No ADI allocated16
Fast green FCF R 0-12.5 mg/kg b.w.6
Saffron R,T Food ingredient17
Sweetening agents
Hydrogenated glucose syrups R ADI "not specified"2
Isomalt R ADI "not specified"2
Mannitol T 0-50 mg/kg b.w.6
Thaumatin S ADI "not specified"2
Thickening agents
Dammer gum S,T No ADI allocated16
Ethylhydroxyethyl cellulose R,T 0-25 mg/kg b.w. 6, 18
Gum ghatti R No ADI allocated16
Karaya gum R 0-20 mg/kg b.w.6
Oat gum O No ADI allocated16
Tragacanth gum R ADI "not specified"2
Xanthan gum S 0-10 mg/kg b.w.
ANNEX 4 (Con't)
ADI for man
Specifications1 and other
toxicological
recommendations
Miscellaneous food additives
Bone phosphate R 70 mg/kg b.w.19
Carbon dioxide R,T ADI "not specified"2
Nitrous oxide R Acceptable20
Polyvinylpyrrolidone (PVP) R,T 0-25 mg/kg b.w.6
Quillaia extract N,T 0-5 mg/kg b.w.
Sodium thiocyanate S Decision postponed
B. Contaminants
Ethylenimine - Provisional acceptance21
ANNEX 4 (Con't)
Specifications only1
Acesulfame potassium S
Ammonium hydrogen carbonate R
Ammonium polyphosphate S,T
Butylated hydroxyanisole R
Calcium polyphosphates S
Calcium, potassium, and sodium R
salts of myristic, palmitic, and
stearic acids
Carrageenan R
Diethyleneglycol monomethylether S,T
Diethyl tartrate R
Ethyl alcohol (previously ethanol) R
Ethylhydroxymethyl cellulose R
Eugenyl methyl ether R
Gum arabic R
Hydrogen peroxide R
Hydroxypropyl cellulose R
Hydroxypropylmethyl cellulose R
Insoluble polyvinylpyrrolidone R
Methylethyl cellulose S
Modified starches:
Acetylated distarch adipate R
Acetylated distarch phosphate R,T
Hydroxypropyl distarch phosphate R
Pentapotassium triphosphate R
Polydimethylsiloxane R
Saccharin R
Sodium aluminium phosphate, R
acidic
Sorbitan monolaurate R,T
Sorbitan monooleate R,T
Sorbitol R
Sucrose acetate isobutyrate R,T
Turmeric oleoresin N
Notes to Annex 4
1. N, new specifications prepared; O, specifications not prepared;
R, existing specifications revised; S, specifications exist,
revision not considered or not required; and T, the existing, new
or revised specifications are tentative and comments are invited.
2. ADI "not specified" means that, on the basis of the available
data (chemical, biochemical, toxicological, and other), the total
daily intake of the substance, arising from its use 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 that reason, and for the
reasons stated in the individual evaluations, the establishment
of an acceptable daily intake (ADI) expressed in numerical form
is not deemed necessary.
3. Acceptable for use in food processing.
4. No information was available on the food use of this enzyme.
5. Polyethylenimine is considered to be a suitable substance for use
as an immobilizing agent in the production of immobilized
enzymes. (See also note 21.)
6. Temporary acceptance.
7. Acceptable level for treatment of flours for cake manufacturing.
8. Group ADI for aluminium salts expressed as aluminium.
9. No information was available on the food use of these salts.
10. Group ADI for silicon dioxide and certain silicates (aluminium,
calcium, and sodium aluminosilicate); the previous ADI "not
limited" was changed to ADI "not specified".
11. Included in the group maximum tolerable daily intake for iron.
12. Group ADI for guanylic acid and its calcium, dipotassium, and
disodium salts.
13. Group ADI for inosinic acid and its calcium, dipotassium, and
disodium salts.
14. Group ADI for sulfur dioxide and sulfites (sodium and potassium
metabisulfites, sodium sulfite, and sodium hydrogen sulfite
expressed as sulfur dioxide).
15. Group ADI for sorbic acid and its calcium, potassium, and sodium
salts expressed as sorbic acid.
16. Insufficient information available on its toxicology and chemical
composition.
17. This substance is regarded as a food rather than as a food
additive.
18. Group ADI for modified celluloses.
19. This figure represents the maximum tolerable daily intake (MTDI)
of phosphates expressed as phosphorus; it applies to the sum of
phosphates naturally present in food and the additives listed in
Annex 4 of the twenty-sixth report (WHO Technical Series, No.
683, 1982). It also applies to diets that are nutritionally
adequate in respect of calcium. However, if the calcium intake
were high, the intake of phosphate could be proportionately
higher; the reverse relationship would also apply.
20. The food use of nitrous oxide as a propellant is acceptable.
21. Acceptable on condition that the amount of ethylenimine migrating
into food is reduced to the lowest technically attainable level.
See Also:
Toxicological Abbreviations
Tragacanth gum (FAO Nutrition Meetings Report Series 46a)
Tragacanth gum (WHO Food Additives Series 5)
TRAGACANTH GUM (JECFA Evaluation)