PECTINS AND AMIDATED PECTINS
Explanation
This substance was evaluated for acceptable daily intake for man
(ADI) by the Joint FAO/WHO Expert Committee on Food Additives in 1973
(see Annex, Ref. 33). A toxicological monograph was issued in 1975
(see Annex, Ref. 35).
Since the previous evaluation, additional data have become
available and are discussed in the following monograph. The previously
published monograph has been expanded and reproduced in its entirety.
BIOLOGICAL DATA
TOXICOLOGICAL STUDIES
Special studies on reproduction
A three-generation reproduction study of amidated pectin was
carried out using groups of eight male and 16 female Charles River
CD strain mice. The test groups were fed 2% or 5% amidated pectin.
Similar groups of animals fed 2% or 5% non-amidated pectin were
utilized as controls. The study design called for two litters to be
raised per generation with the second (b) litter utilized to produce
the next generation. In general, there were no dose-related effects on
mortality, body weight, food consumption, reproductive or survival
indices or incidence of gross or histopathologic lesions. Mating of
the 2% non-amidated pectin group to produce the F2b litter resulted
in only five females becoming pregnant, two died during pregnancy and
none of the pups survived to day 21. Since the occurrence was limited
to the second litter of one generation and did not occur at a higher
dose (5%) the effect is not considered to be related to administration
of non-amidated pectin. There was some mortality among the other
groups and generations as well, evidently due to respiratory
infections (Industrial Biotest, 1979b).*
Groups of one male and five female Wistar rats were utilized in
carrying out a two-generation reproduction study of amidated pectin
fed at a level of 16.6% in the diet. One set of litters were produced
per generation. Five males and five females per generation were
subjected to gross and histopathologic examination. No abnormalities
were reported to occur in any of the offspring and the results of the
* This study was validated by an independent audit (see memo of 13
November 1979, International Verband de Pektinprodunzenter -
submitted to WHO).
gross and histopathologic examination were said to be normal. Data
such as reproductive and survival indices, body weight changes, etc.
were not presented in the report (Mosinger, 1976).
Special studies on teratology
Groups of 20 or 22 pregnant females Charles River albino rats
were fed a diet containing 2 or 5% amidated pectin on gestation days 6
through 15. Similar groups fed diets containing 2 or 5% non-amidated
pectin were used as concurrent controls. Dams were sacrificed on day
20 and foetuses were examined externally. Two-thirds of the foetuses
were processed for skeletal examination and one-third for soft tissue
examination. There was no mortality among the dams during the study
and body weights and food consumption were comparable between groups.
Data on corpora lutea, implantation sites, resorption sites, foetal
viability, foetal weight and sex ratio were comparable between all the
groups. No intergroup differences were reported with respect to
skeletal or soft tissue anomalies (Industrial Biotest, 1976).*
Short-term studies
Rat
Four groups of 10 male and 10 female rats were fed 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 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).
* This study was validated by an independent audit (see memo of 13
November 1979, International Verband de Pektinprodunzenter -
submitted to WHO).
Long-term studies
Groups of 20 male weanling Wistar rats were fed diets of purina
laboratory meal to which was added low molecular pectin (approximately
18% amidated) or non-amidated pectin 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/g. Mortality did not vary significantly between groups.
Body weights for the pectin fed groups were similar but significantly
less than those of the control animals. A comparison of grams of
diet/kg 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-weight ratio 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 were
examined histologically. No compound related effects were observed
(Palmer & Jones, 1974; Abdul & Palmer, 1974).
Groups of 50 male and 50 female Charles River strain albino rats
were fed amidated pectin at dietary levels of 2% and 5% for two years.
Similar groups of rats were fed non-amidated pectin at 2% or 5% of the
diet. Initially an untreated control group receiving chow diet only
was included in the study, however, this group was sacrificed and
discarded at week 36 of the study. The group fed non-amidated pectin
served as the control for the amidated pectin groups. An interim
sacrifice of 10 animals per group per sex was carried out after three
months of testing. Body weight tended to be lower in the males fed 5%
of amidated or non-amidated pectin as compared to the males fed 2%
amidated or non-amidated pectin. The difference was statistically
significant at a number of weeks during the study. The total weight
gain at 13 weeks was significantly lower in the males given 5%
non-amidated pectin than that of the non-amidated 2% group. No
significant changes were noted in food consumption or mortality. Small
statistically significant differences between the high dose amidated
and non-amidated group occurred with respect to leucocyte and
reticulocyte counts at the three-month repeat blood collection,
otherwise no significant haematological changes were noted. The 2%
amidated pectin females had a large increase (about 3x) in serum
glutamin pyruvate levels at the three-month and three-month repeat
blood collections. There were other scattered instances of small
statistically significant between group differences with respect to
other clinical chemistry parameters. No significant changes were noted
upon urinalysis. There were scattered instances of small but
statistically significant between group differences in absolute organ
and relative organ weights.
The absolute and relative adrenal glands weight in the low dose
amidated pectin group was high compared to the other groups, although
evidently there was not a statistically significant between group
difference. The adrenal weights were not increased in the high dose
females.
In general, the incidence of neoplastic and non-neoplastic
lesions was similar in all the groups. The incidence of chronic
inflammation of the liver was 4/37 in the females given 2% non-
amidated pectin, 3/40 in the females given 5% non-amidated pectin,
14/39 in the females fed 2% amidated pectin and 13/49 in the females
given 5% amidated pectin. Although the incidence of this lesion was
increased in the females given amidated pectin, there was no dose
response, the incidence being slightly reduced in the 5% amidated
pectin group as compared to the 2% group (Industrial Biotest, 1979a).*
A group of 20 male and 20 female Wistar rats were fed a diet
containing 16.6% amidated pectin for two years. Growth, final body
weight and incidence of neoplastic and non-neoplastic lesions were
stated to be comparable to a group of 4000 historical control animals
maintained in the performing laboratory. Pathology observations for
each animal were provided, but body weight other than at termination,
and food consumption data were not reported (Mosinger, 1976).
Wistar rats of the Centre for Investigation and Medical Research
at Marseille strain were administered 100 mg/kg bw of 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 an identical group of rats fed the basic
synthetic diet. At this level of pectin in the diet there appeared to
be no effects on growth and body weights of fed animals as compared to
historic controls. Also, there appeared to be no effects on the serum
of fed rats. Since many of the experimental details are lacking it is
difficult to reconstruct the complete design of the study. It is
clear, however, that tissues from 20 males and 20 females sacrificed
at 24 months were studied histologically. Rats dying prior to
termination of the study were also said to have been examined
microscopically. However, no mention of such animals is made in the
detailed pathology. The histopathology revealed no adverse effects on
the stomachs or testes of fed males. It should be noted that these
* This study was validated by an independent audit (see memo of 13
November 1979, International Verband de Pektinprodunzenter -
submitted to WHO).
were very small rats. Only one male reached 640 g, the remainder
ranged from 210 to 420 g with seven of the rats weighing 270 g or
less. The weight of the females at sacrifice was similar to the males.
A first generation produced by mating five animals produced a total of
99 offspring and a second generation produced by mating five animals
resulted in only 43 offspring (Mosinger, 1974).
Comments
Non-amidated 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 non-amidated 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.
A three-generation reproduction study and a teratogenicity study,
and a two-year feeding study in rats fed diets containing 2% and 5%
amidated pectin or non-amidated pectin showed no significant
toxicological differences between animals fed amidated and non-
amidated pectin.
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
Abdul, H. & Palmer, G. H. (1974) Twp-year pectin feeding study:
histopathological studies. Unpublished report from Sunkist
Growers, Inc. submitted to the World Health Organization by
Sunkist Growers, Inc.
Industrial Biotest (1976) Teratologic study on amidated pectin.
Unpublished report submitted to the International Pectin
Producers Association
Industrial Biotest (1979a) Two-year study on amidated pectin.
Unpublished report submitted to the International Pectin
Producers Association
Industrial Biotest (1979b) Three generation reproduction study on
amidated pectin. Unpublished report submitted to the
International Pectin Producers Association
Mosinger, M. (1974) Experimentation d'epreuve concernant les effets de
l'administration orale prolongée du produit pectine L.H. NST de
la Société Unipectine SA. Unpublished report from the "Central
d'explorations et de recherches médicales", Marseille, submitted
to the World Health Organization by the International Pectin
Producers Association
Mosinger, M. (1976) Two-year chronic feeding study and multi
generation reproductive-teratology study with amidated pectin.
Unpublished report submitted to the International Pectin
Producers Association
Palmer, G. H. & Jones, T. R. (1974) Two-year pectin feeding study.
Unpublished report from Sunkist Growers, Inc. submitted to the
World Health Organization by Sunkist Growers, Inc.
Til, H. P., Seinen, W. & De Groot, A. P. (1972) Sub-chronic (90-day)
toxicity study with two samples of pectin (Melange A2 and C2)
in rats. Unpublished CIVO Report No. 3843 studied August 1972,
Submitted to the World Health Organization by the Inst. Eur. des
Ind. de la Pectine
See Also:
Toxicological Abbreviations