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.
PECTIN (AMIDATED)
Explanation
This substance has been evaluated for acceptable daily intake by
the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1,
Refs Nos 19 and 34) in 1969 and 1973.
Since the previous evaluation additional data have become
available and are summarized and discussed in the following monograph.
The previously published monographs have been expanded and are
reproduced in their entirety below.
BIOLOGICAL DATA
BIOCHEMICAL ASPECTS
These partially methoxylated polygalacturonic acids occur
naturally and widely in fruits especially citrus fruits and apples and
are part of the cell walls. They are therefore part of the normal
diet. For the past 30 years some newer pectins have been in use, in
which the de-esterified carboxyl groups have been partially amidated.
At one time pectins have been used as plasma extenders as 1%
solution but large intravenous doses have led to pectin deposition in
the kidney, liver and lungs with consequential degenerative changes
(Merck Index, 1968).
Pectin has been shown to lower blood cholesterol in man (Keys et
al., 1961) and in the rat (Wells & Ershoff, 1961). Four groups of
three male and three female pigs were given diets for four weeks
supplemented with either 5% pectin or 5% cellulose with or without
dietary cholesterol. Pectin had no effect on body weight or plasma
cholesterol level unless cholesterol was given in the diet. Pectin
lowered significantly alimentary hypercholesterolaemia (Fisher et al.,
1966; Fisher & Kannitz, 1964). Chicken fed cholesterol in the diet
excrete more cholesterol if pectin is also added. Pectin has no effect
on endogenous plasma cholesterol or may raise the level (Fisher et
al., 1964). On the other hand swine fed pectin developed significantly
higher blood cholesterol levels in other experiments (Fausch &
Anderson, 1965).
The digestibility of pectin was determined in groups of six rats
fed 17.4% or 34.8% pectin in their diet for three weeks. At the lower
dietary level there was no adverse effect on the utilization of other
nutrients but at the higher level utilization of other nutrients was
reduced. Pectin produced diarrhoea and growth was retarded at both
dietary levels. Faecal recovery showed only 20% of orally ingested
pectin to be digestible (Carey, 1958).
Four normal dogs and two dogs with ileostomies were fed 140 g of
pectin in a mixed diet over a seven-day period. An average of 90% of
pectin was broken down. When fed during fasting periods an average of
only 50% was broken down. In the case of studies with humans more
pectin was broken down than in the dog study. A study involving two
human patients with ileostomies showed that the breakdown of pectin
occurred in the colon rather than in the upper intestine, and that
bacterial enzymes were involved rather than enzymes of the animal
organism (Werch & Ivy, 1941).
Rats were fed diets containing 0.04 ppm Pb210 and either 5%
pectin or 5% starch. The control group retained 15.8% of the
radioactive lead and excreted 10.9% in the urine and 71.7% in the
faeces. The pectin-fed animals retained an average of 24% less lead
than controls, significantly less being excreted in the urine and more
in the faeces (Murer & Crandall, 1942).
TOXICOLOGICAL STUDIES
Acute toxicity
None available.
Short-term studies
Rat
Rats were fed 2.5-10% pectin without any deleterious effects - no
details are available (Ershoff & McWilliams, 1945).
In another experiment four groups of 10 male and 10 female rats
were fed diets containing 0, 5%, 10% or 15% pectin (nonamidated) for
90 days. No adverse effects were noted on general condition, behaviour
and survival. Growth was slightly decreased at the 15% level, an
observation previously noted in a range-finding test using 20% pectin.
At 20% also reduced food consumption and food efficiency had been
noted. Total serum protein and albumin were decreased at the 15%
level but the haematological indices showed no treatment related
differences. Blood chemistry showed no significant findings. The
relative caecal weight was increased at the 15% level, a phenomenon
also seen with modified starches and other high food intake of complex
carbohydrates. Gross and histopathology were essentially normal (Til
et al., 1972).
In another experiment four groups of 10 male and 10 female rats
were fed on diets containing 0, 5, 10 or 15% pectin (21% amidated) for
90 days. No adverse effects were noted on general condition, behaviour
and survival. Growth was slightly decreased at the 15% level and this
finding was also noted in a range finding test using 20% pectin in the
diet. Some decrease in growth occurred inconsistently also at the 10%
dietary level. Food intake and food efficiency were not affected at
any level. Haematological parameters showed no significant treatment
related changes. Total serum protein and albumin were reduced at the
15% level but the other clinical biochemical parameters and urinalysis
were essentially normal. Caecal weights were increased at all levels
but in a dose-related manner. These findings are reminiscent of what
is seen when high amounts of starch, modified starch or certain other
carbohydrates are fed. Gross and histopathology were normal but a
slight degree of hyperkeratosis of the forestomach in some males was
seen at the 10% and 15% level but is probably not of toxicological
significance (Til et al., 1972).
Long-term studies
Rat
Groups of 20 male weanling Wistar rats were fed diets of Purina
laboratory meal to which was added L.M. Pectin (approximately 18%
amidated) or Pectin, N.F. at 10% of the diet. Control diets contained
10% alphacellulose (Alphacel). The rats were fed for two years. The
diets were made isocaloric by supplementing the alphacel with dextrose
assuming a caloric equivalent for pectin of 0.6187 cal./mg.
Mortality did not vary significantly between groups. Body weights
for the pectin fed groups were similar but significantly less than
that of the control animals. A comparison of grams of diet/kgm body
weight showed a slightly greater food utilization for the pectin fed
groups. The controls, however, consumed more food and gained more
weight. There was no significant difference in average organ to body
weight ratios for adrenal, heart, kidney, liver and spleen. The
testes/body of the pectin fed groups did not differ from each other
but both were significantly larger than those of the control group.
Blood chemistry, SGOT and SPGT done at sacrifice showed no
abnormalities in the pectin groups.
Gross examination at necropsy showed no unusual findings. Two
tumours were noted in the control group and one in the amidated pectin
group.
All gross lesions and adrenal, heart, kidney, liver, lung, spleen
and testes will be examined histologically (Palmer, G. H. & Jones,
T. R., 1974).
Wistar rats of the Center for Investigation and Medical Research
at Marseille strain were administered 100 mg/kg bw of, and 18.4%,
amidated pectin, daily in the synthetic diet of Lacassagne MABI.
Feeding was ad lib.
Groups of 20 males and 20 females housed five to a cage were
used. Controls consisted of a group of 450 rats fed the basic
synthetic diet.
Although the design of the experiment is not apparent the author
mentions the littering of two generations. The author also stated
there was no difference in growth and body weights of fed animals as
compared to historical controls. Likewise electrophoretic examination
of blood drawn just prior to sacrifice did not differ from controls. A
complete histologic examination was carried out on 20 males and 20
females after 24 months on experiment. Tissues of fed animals did not
differ from those of the controls. The author states further that no
adverse effects were noted on the ability of the animals to reproduce
nor was the substance shown to be teratogenic (Mosinger, M., 1974).
Comments:
Nonamidated pectins and their salts as specified are normal
constituents of the human diet and have also been administered
intravenously at high levels to man without acute toxic effects. The
available short-term tests show that even at 5% dietary levels no
adverse effects are seen. The caecal enlargement without any
accompanying histological changes is probably related to the presence
of large amounts of a polysaccharide in the diet.
Amidated pectins produced mild growth depression at a lower level
(10%) than was seen with nonamidated pectins in a 90-day test as well
as in a two-year study in rats. The available short-term study in rats
revealed caecal enlargement but not associated with any histological
abnormality. The available one-generation reproduction study and the
two-year studies in rats lack histopathological and biochemical
details. They cannot therefore be used for evaluation.
EVALUATION
Level causing no toxicological effect
Rat: 5% (= 50 000 ppm) in the diet equivalent to 2500 mg/kg bw.
Estimate of acceptable daily intake for man
0-25 mg/kg bw.*
* Temporary.
FURTHER WORK OR INFORMATION
Required by June 1978.
The results of histological examinations in the long-term
studies. Adequate reproduction and embryotoxicity including teratology
studies.
REFERENCES
Carey, P. L. (1958) Thesis submitted to Purdue University
Ershoff, B. H. & McWilliams, H. B. (1945) Amer. J. dig. Dis., 12, 21
Fausch, H. D. & Anderson, T. A. (1965) J. Nutr., 85, 145
Fisher, H. & Kannitz, H. (1964) Proc. Soc. Expl. Biol. Med., 116, 278
Fisher, H. et al. (1964) Science, 146, 1063
Fisher, H. et al. (1966) J. Atheroscler. Res., 6, 190
Keys, A., Grande, F. & Anderson, J. T. (1961) Proc. Soc. Expl. Biol.
Med. (N.Y.), 106, 555
Merck Index (1968)
Mosinger, M. (1974) Center for Investigation and Medical Research,
Marseilles
Murer, H. K. & Crandall, L. A. jr (1942) J. Nutr., 23, 249
Palmer, G. H. & Jones, T. R. (1974) Unpublished data Sunkist Growers
Inc.
Til, H. P., Seinen, W. and de Groot, A. P. (1972) CIVO Report No. 3843
dated August 1972
Wells, A. F. & Ershoff, B. J. (1961) J. Nutr., 86, 113
Werch, S. C. & Ivy, A. C. (1941) J. Digest. Dis., 8, 101
See Also:
Toxicological Abbreviations
Pectin (amidated) (WHO Food Additives Series 8)