Toxicological evaluation of some food
    additives including anticaking agents,
    antimicrobials, antioxidants, emulsifiers
    and thickening agents


    The evaluations contained in this publication
    were prepared by the Joint FAO/WHO Expert
    Committee on Food Additives which met in Geneva,
    25 June - 4 July 19731

    World Health Organization


    1    Seventeenth Report of the Joint FAO/WHO Expert Committee on
    Food Additives, Wld Hlth Org. techn. Rep. Ser., 1974, No. 539;
    FAO Nutrition Meetings Report Series, 1974, No. 53.



         This substance has been evaluated for acceptable daily intake by
    the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1,
    Ref. No. 19) in 1969.

         Since the previous evaluation, additional data have become
    available and are summarized and discussed in the following monograph.
    The previously published monograph has been expanded and is reproduced
    in its entirety below.



         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 (Fischer
    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 otherhand 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).

         Rats were fed diets containing 0.04 ppm (0.000004%) 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).

         Four normal dogs and two dogs with ileotomies were fed 140 g of
    pectin in a mixed diet over a seven-day period. An average of 90% of
    the 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 ileotomies, 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).


    Acute toxicity

         None available.

    Short-term studies


         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 (non-amidated) 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 fore-stomach 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

         None available.


         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 15% dietary levels no
    adverse effects are seen. The caecal enlargement without any
    accompanying histological changes is considered to be related to the
    presence of large amounts of a polysaccharide in the diet. Little
    formal testing has been carried out and does not appear necessary for
    the natural non-amidated product. On the other hand amidated pectins
    appear to be somewhat more toxic and only the 5% level produces no
    adverse effects apart from the expected caecal enlargement.


    1.   Non-amidated pectin

         Not limited.*

    2.   Amidated pectin

    Level causing no significant toxicological effect

         Rat: 50 000 ppm (5%) in the diet equivalent to 2500 mg/kg bw.

    Estimate of acceptable daily intake for man

         0-25 mg/kg.**


    *    See relevant paragraph in the seventeenth report, pp. 10-11.

    **   Temporary.


         Required by 1974. Provision of full specification.


    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. et al. (1966) J. Atheroscler. Res., 6, 190

    Fisher, H., Griminger, P. & Weiss, H. S. (1964) Science, 145, 1063

    Fisher, H. & Kannitz, H. (1964) Proc. Soc. Exp/l Biol. Med., 116, 278

    Keys, A., Grande, F. & Anderson, J. T. (1961) Proc. Soc. Exp/l Biol.
         Med. (N.Y.) 106, 555

    Merck Index (1968)

    Murer, H. K. & Crandall, L. A. jr (1942) J. Nutr., 23, 249

    Til, H. P., Seinen, W. & 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  (FAO Nutrition Meetings Report Series 46a)