INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
WORLD HEALTH ORGANIZATION
TOXICOLOGICAL EVALUATION OF SOME
FOOD COLOURS, EMULSIFIERS, STABILIZERS,
ANTI-CAKING AGENTS AND CERTAIN
OTHER SUBSTANCES
FAO Nutrition Meetings Report Series
No. 46A WHO/FOOD ADD/70.36
The content of this document is the result of the deliberations of the
Joint FAO/WHO Expert Committee on Food Additives which met in Rome,
27 May - 4 June 19691
Food and Agriculture Organization of the United Nations
World Health Organization
1 Thirteenth report of the Joint FAO/WHO Expert Committee on Food
Additives, FAO Nutrition Meetings Report Series, in press;
Wld Hlth Org. techn. Rep. Ser., in press.
CARRAGEENAN AND FURCELLARAN
This material contains sulfated galactose units.
Biological Data
Biochemical aspects
Rats excrete carrageenan quantitatively in the faeces if administered
in the diet at levels of 2-20 per cent. and it therefore has no direct
nutritive value (Hawkins & Yaphe, 1965). Oral administration of
undegraded carrageenan to guinea-pigs up to 158 mg causes no
detectable excretion in the urine. However, if given intraduodenally
to guinea-pigs with ligated pylorus, it exerts an antigastric effect.
Hence, absorption is still a possibility although its molecular size
is very large (Anderson & Soman, 1966). Groups of six rats were fed
diets containing 17.4 or 34.8 per cent. carrageenan for three weeks.
Weight gain was significantly reduced especially at higher levels.
Food efficiency showed interference with utilization of other
nutrients in the diet. Only 10-15 per cent. appeared digestible as
estimated from faecal examination (Carey, 1958). Using nine groups of
three, four or five guinea-pigs it was noted that single intravenous
injections of degraded carrageenan leads to a dose-related increase in
urinary polysaccharides. Oral or intraduodenal administration of
degraded carrageenan gave detectable residues in the urine and had an
antigastric activity in guinea-pigs with ligated pylorus. However the
amounts absorbed are very small and some additional protective
mechanism may be involved (Anderson & Soman, 1966). Carrageenan
inhibits pepsin action by binding the substrate (Anderson & Watt,
1959; Piper & Fenton, 1961; and Houck & Bhayana, 1960). Interference
with pepsin activity depends on concentration of carrageenan and
protein. It occurs only over a narrow range (Márquez & Garcia, 1960;
Vaughan et al., 1961; and Vaughan et al., 1962). At a level of five
per cent. in the diet of rats carrageenan had no effect on utilization
of casein, soybean protein, or of other proteins of variable quality
(Friedman & Douglass, 1960).
No difference in protein economy of the growing rat was observed with
a diet of 0.5-5 per cent. carrageenan and either a high quality
protein (casein) or a low quality vegetable protein (USFDA, 1969).
Subcutaneous injected carrageenan stimulates the biosynthesis of
collagen and the formation of connective tissue (Robertson & Schwartz,
1953; and Jackson, 1956). Three per cent. carrageenan in the diet has
been reported to reduce the plasma cholesterol level in chicks by 50
per cent. (Riccardi & Fahrenbach, 1965). Carrageenan acts as an
antithrombic in both human and dog blood plasma (Hawkins & Leonhard,
1962). The presence of carrageenan in infant feeds does not affect the
availability of any added iron (Gorten et al., 1963; Gorten & Cross,
1964; Owen & Fomon, 1963; Fomon et al., 1961).
A seven-month infant feeding study of the nutritional value of Formil
an infant formula containing carrageenan (concentration not stated),
showed normal results in feeding pattern, growth, bowel function; and
serum calcium, phosphorus and cholesterol levels (Marine Colloids,
Inc., 1969).
Acute toxicity
Intravenous injection of undegraded carrageenan is very toxic to
rabbits (Anderson & Duncan, 1961).
Intravenous injection of 50 mg killed rabbits within 48 h. These
animals showed total obstruction of the glomerular capillaries by a
fibrinoid-like substance, and extensive tubular neurosis. Rabbits
survived 10 mg intravenously, but showed histopathologic changes in
the kidney. Similar results were obtained in rats and guinea-pigs.
Guinea-pigs survived intravenous injection of 5-10 mg/kg (Morard et
al., 1964). Intravenous carrageenan in doses of 1 mg/kg kills
guinea-pigs within 30 mins (Anderson & Soman, 1966). The injection of
lambda-carrageenan induced collagenous growth in the rabbit cornea
(Dass & McCandless). A single injection of 5 ml of a one per cent.
carrageenan solution produced sarcomata in female rats and fibrous
degeneration of mammillary gland epithelium with hyaline thickening of
capillary walls (Cater, 1961).
Short-term studies
Rat. Groups of six male rats were fed for a 10-week period 0, 5, 10
and 20 per cent. of a refined preparation. The animals grew well
except at the highest test level which showed a 50 per cent. mortality
(Nilson & Schaller, 1941). In similar feeding experiments using 10
rats there was some growth retardation, decreased food intake and
reduced urinary nitrogen excretion at dietary levels over 10 per cent.
(Hawkins & Yaphe, 1965).
Guinea-pig. Fifty male guinea-pigs were injected daily for 1-41 days
with 0.25 mg histamin/100 g body weight in order to induce gastric
ulceration. Fifty per cent. carrageenan in the diet did not accentuate
the mucosal lesions (Holzmann & Schott, 1963).
Man. In a nutritional study of tocopherol requirements an infant
formula (Similac) containing carrageenan was fed as the basic diet for
six months to 44 healthy premature infants (Goldbloom, 1963).
Long-term studies
Mouse. Groups of five male and five female mice of two strains were
maintained over their life span on diets containing 0, 1 per cent., 5
per cent., 15 per cent. and 25 per cent. carrageenan without apparent
ill-effects on growth, survival, gross and histopathology of the
gastro-intestinal tract, liver and kidneys (Nilson & Wagner, 1959).
Rat. Groups of five male and five female rats of two strains were
fed 0, 1 per cent., 5 per cent., 15 per cent. and 25 per cent.
carrageenan for their life span. Food consumption increased in
proportion to the increased carrageenan content. No effect was noted
on mortality. At the 25 per cent. level there was evidence of hepatic
cirrhosis but all other levels showed no histopathological
abnormalities of the intestinal tract, liver, kidneys. (Nilson &
Wagner, 1959).
Comments
These closely related polysaccharides are very little absorbed when
ingested by several animal species. The available short- and long-term
studies support the safety of these materials despite the small
numbers of animals employed. Carrageenan has a long history of human
use without known ill-effect.
EVALUATION
Level causing no toxicological effect in the rat
10 per cent. (= 100 000 ppm) in the diet equivalent to 5000 mg/kg body
weight/day
Estimate of acceptable daily intake for man
mg/kg body weight
Unconditional acceptance 0-501
REFERENCES
Anderson, W. & Watt, J. (1959) J. Pharm. (Lond.), 11, 318
Anderson, W. & Duncan, J. G. C. (1965) J. Pharm. (Lond.), 17, 647
Anderson, W. & Soman, P. D. (1966) J. Pharm. (Lond.), 18, 827
Carey P. L. (1958) Thesis submitted to Purdue University
Cater, D. B. (1961) Brit. J. Cancer, 15, 607
Dass. B. & McCandless, E. L. (1966) Fed. Proc., 25, 706
Fomon, S. J., Owen, G. M. & Thomas, L. N. (1961) Amer. J. Dis.
Child., 108, 601
1 As carrageenan or furcellaran or the sum of both.
Friedman, L. & Douglass, C. D. (1960) Unpublished summary report
submitted by Marine Colloids Inc.
Goldbloom, R. B. (1963) Pediatrics, 32, 36
Gorten, M. K., Hepner, R. & Workman, J. B. (1963) J. Pediat., 63,
1063
Gorten, M. K. & Cross, E. R. (1964) J. Pediat., 64, 509
Hawkins, W. W. & Leonhard, V. G. (1962) J. Lab. clin. Med., 60, 641
Hawkins, W. W. & Yaphe, W. (1965) Canad. J. Biochem., 43, 479
Holzmann, H. & Schott, H. J. (1963) Naturwissenschaften, 50, 502
Houck, J. C. & Bhayana, J. L. (1960) Gastroenterology, 39, 196
Jackson, D. S. (1956) Biochem. J., 62, 250
Marine Colloids Inc. (1969) Unpublished report
Márquez, V. M. & Garcia, R. G. (1960) Rev. Fac. Pharmac.
(Venezuela), 3, 237
Morard, J. C. et al. (1964) Nature, 202, 401
Nilson, H. W. & Schaller, J. W. (1941) Food Res., 6, 461
Nilson, H. W. & Wagner, J. A. (1959) Food-Res., 24, 235
Owen, G. M. & Fomon, S. J. (1963) Midwest Soc. Pediat. Res., 63, 490
Piper, D. W. & Fenton, B. (1961) Gastroenterology, 40, 638
Riccardi, B. A. & Fahrenbach, M. J. (1965) Fed. Proc., 24, 263
Robertson, W. B. van & Schwartz, B. (1953) J. biol. Chem., 201, 689
United States Food and Drug Administration (1969) Unpublished summary
report
Vaughan, O. W., Rezabek, H. & Filer, L. J. (1961) Fed. Proc., 20,
863B
Vaughan. O. W., Filer, L. J. jr & Churella, H. (1962) Agric. Fd
Chem., 10, 517
See Also:
Toxicological Abbreviations
Carrageenan and Furcellaran (WHO Food Additives Series 5)
Carrageenan and furcellaran (WHO Food Additives Series 19)