WHO Food Additives Series 1972, No. 1


    The evaluations contained in this publication were prepared by the
    Joint FAO/WHO Expert Committee on Food Additives which met in Rome,
    16-24 June 19711

    World Health Organization




    1 Fifteenth Report of the Joint FAO/WHO Expert Committee on Food
    Additives, Wld Hlth Org. techn. Rep. Ser., 1972, No. 488; FAO
    Nutrition Meetings Report Series, 1972, No. 50.

    The monographs contained in the present volume are also issued by the
    Food and Agriculture Organization of the United Nations, Rome, as FAO
    Nutrition Meetings Report Series, No. 50A

    (c) FAO and WHO 1972


    Biological data

    Biochemical aspects

    In vitro hydrolysis by simulated gastric and intestinal juices shows
    practically no effect of gastric juice, while intestinal juice
    hydrolyses 25 per cent. of the ester in 4 h., 65 per cent. in 12 h.
    and 80 per cent. in 24 h. (MeNeely & Shepherd, 1966).

    Alginic acid and alginates and also the algae from which these
    substances derive have been used in man for many years.  Propylene
    glycol is rapidly absorbed from the gut and metabolized in a variety
    of ways to acetate, lactate or glycogen.

    Propylene glycol alginate, labelled uniformly with 14C either in the
    alginate or the propylene glycol moiety, was administered to 8 mice.
    Absorption, distribution through the body tissues and excretion of the
    radio-label was followed from 1 hour to 5 days after administration by
    whole body autoradiography.  The alginate moiety and unhydrolysed
    ester are not absorbed from the gastrointestinal tract.  Any
    hydrolysed propylene glycol is absorbed and metabolized by the usual
    pathways.  A single dose of 1000 mg/kg is virtually completely
    eliminated within 5 days but after 5000 mg/kg traces of activity were
    still noted in the rectum.  Absorbed labelled propylene glycol had
    disappeared completely from the body after 3 days (Sharratt & Dearn,
    1971).  14C-labelled alginate prepared from Laminaria digitata was
    not absorbed to any significant extent by rats when fed at 10 per
    cent. of their diet (Humphreys & Triffit, 1968).

    Acute toxicity

    No LD50s are available.  Rabbits injected intravenously,
    intraperitoneally, intramuscularly or subcutaneously with 6.2 mg, 12.5
    mg or 25 mg/kg body-weight showed no toxic effects systematically or
    at the site of injection (Steiner & MeNeely, 1951).  When injected
    subcutaneously or intramuscularly with up to 2 ml of sterile aqueous 2
    per cent. solutions of the compound no gross or histological
    abnormalities occurred at the injection site.  Intraperitoneal and
    intravenous injections of similar amounts produced no abnormal
    systemic effects (Ouer, 1949).

    Of 50 human subjects known to be allergic to numerous other substances
    11 showed very slight to moderate skin reactions to the intradermal
    test.  When 5 of those that showed the greatest reactions were fed
    propylene glycol alginate 3 showed mild allergic reactions which were
    duplicated in repeated tests.  Of 50 non-allergic individuals 3 showed
    very slight skin reactions, but none had reactions to oral
    administration (Ouer, 1949).

    Special studies

    1, 2-propylene glycol has a no-effect level of 2000 ppm level when
    tested for embryo toxicity in the chick (McLaughlin et al., 1965)
    while 1,3-propylene glycol appeared to produce chondrodystrophy in a
    high percentage of embryos (Gebhardt, 1968).  The toxicology of
    propylene glycol has been reviewed (FAO/WHO, 1970; Bost & Ruckebusch,

    Bacteriological examination of the intestinal flora of 2 rats after 6
    months on basal diet and 21 days of 5 per cent. added propylene glycol
    alginate showed a fall in lacto-bacilli and aerobic counts with a rise
    in coliforms and no change in anaerobic counts (Woodard, 1959).

    Short-term studies


    Two groups of 6 female rats each were fed either a diet containing
    21.5 per cent. of the compound and 21.5 per cent. glucose or a normal
    diet with additional 21.5 per cent. glucose for 4 weeks.  After
    sacrificing 2 animals in each group the remaining 4 animals per group
    were fed a normal diet for 4 weeks.  Thereafter, the original control
    group was fed a diet containing 21.5 per cent. of the compound and the
    original test group was kept on control diet for 2 weeks.  The test
    group showed slight growth retardation but appearance and behaviour
    remained normal.  The faeces of the test group tended to be slimy.
    Histopathology of intestine, kidney and liver of the 2 sacrificed
    animals (test and controls) showed no abnormalities (MRCL, 1951).


    Four groups of 3 animals each were fed a diet containing 0, 5, 10 and
    15 per cent. of the compound for 26 weeks.  No adverse effects on
    weight gain, food intake, were seen and histopathology of various
    organs demonstrated no significant lesions (Nilson & Wagner, 1951).


    Eight cats and 1 control were fed a diet with 0, 5, 10 and 15 per
    cent. of the compound for 88-100 days.  At dietary levels of 10 and 15
    per cent. animals showed frequent soft stools.  No signs of toxicity
    were noted, autopsy and histopathology revealed nothing of
    significance (Nilson & Wagner, 1951).


    Three groups of 3 male and 3 female beagles were fed diets containing
    0, 5 and 15 per cent. of the compound for 1 year.  All groups showed
    normal weight gains, food consumption, haemograms, blood urea
    nitrogen, serum alkaline phosphatase, blood glucose and urinalysis.  A
    complete histopathological examination showed no significant lesions
    (Woodard, 1959).


    Four groups of 13-day-old chicks were fed on a diet containing 0, 5,
    10 and 15 per cent. of the compound for 3-7 weeks.  All treated groups
    showed reduced growth rate due to difficulty with the diet but no
    evidence of toxic effects.  Histopathology showed slight evidence of
    transient reversible tissue changes in all groups (Nilson & Wagner,

    Long-term studies


    Four groups of mice were kept on diets containing 0, 5, 10 and 25 per
    cent. of the compound for 12 months.  At the high levels mortality was
    increased and weight gain as well as food intake reduced but
    histopathology was unremarkable (Nilson & Wagner, 1951).


    Four groups of 10 male and female rats were fed over their life span
    diets containing 0, 5, 15 and 25 per cent. propylene glycol alginate.
    A fifth group received 15 per cent. of the compound in a different
    basal diet.  Life span was slightly reduced at the 15 per cent. and 25
    per cent. level.  The bulky diet caused loose faeces.  The group on 15
    per cent. in a different basal diet had normal faeces and was
    sacrificed at 37 weeks.  No adverse effects on weight gain, food or
    water consumption were noted.  Histology showed no lesions
    attributable to the compound (Nilson & Wagner, 1951).

    Forty male and 40 female rats were kept on a diet containing 0 and 5
    per cent. of the compound for 2 years.  After 4-5 months feeding some
    animals were mated.  The F1 generation was fed on similar diets,
    mated after 4 months, and the F2 generation also kept on similar
    diets.  At the end of 2 years the survival rates were 67 per cent.
    male and 78 per cent. female in test groups and 56 per cent. and 50
    per cent. in the respective control groups.  The P generation survived
    761 days, the F1 and F2 generations were sacrificed at 202 and 212
    days respectively.  No difference from the controls was noted
    regarding mean body-weight, general condition, mortality, fertility,
    lactation and survival of the three generations.  Haematology was
    normal; gross and histopathology showed nothing significant (Morgan,
    F. C.).


    Long-term studies in two species are available although the mouse
    study extends over only 12 months.  Effects upon reproduction were
    assessed in the long-term study on rats through two filial
    generations.  In vivo metabolic studies using labelled alginate and
    propylene glycol moieties show that only the propylene glycol moiety
    is absorbed and metabolized.  The alginate moiety is excreted
    unchanged in rats and mice.  A true estimate of the extent of in vivo

    gastrointestinal hydrolysis is desirable to help in estimating the
    contribution by propylene glycol alginate to the total dietary
    propylene glycol intake.


    Level causing no significant toxicological effects in the rat

    Five per cent. (50 000 ppn) in the diet equivalent to 2500 mg/kg

    Estimate of acceptable daily intake for man    mg/kg body-weight

         Unconditional acceptance                     0-251


    Bost, J. & Ruckebusch, Y. (1962) Thérapie, 17, 83

    FAO/WHO (1970) WHO/Food Add./70.36

    Gebhardt, D. 0. E. (1968) Teratology, 1, 153

    Humphreys, S. E. R. & Triffit, J. T. (1968) Nature (Lond.), 219,

    McLaughlin et al., (1965) Toxicol. appl. Pharmacol., 7, 491

    McNeely, W. H. & Shepherd, V. M. (1966) Report to Kelco Co. Labs.

    Medical Research Council Laboratories (1951) Unpublished report

    Morgan, F. C. cited in Woodard, G. (1959) Unpublished report

    Nilson, H. W. & Wagner, J. A. (1951) Proc. Soc. exp. Biol. (N.Y.),
    76, 630

    Ouer, R. A. (1949) Ann. Allergy, 7, 681

    Sharratt, M. & Dearn, P. (1971) Unpublished report submitted by

    Steiner, A. B. & MeNeely, W. H. (1951) Ind. Eng. Chem., 43, 2073

    Woodard, G. (1959) Unpublished report


    1 The contribution from propylene glycol alginate to total dietary
    propylene glycol intake from all sources should be included in the ADI
    for propylene glycol.

    See Also:
       Toxicological Abbreviations
       Propylene glycol alginate  (FAO Nutrition Meetings Report Series 46a)
       Propylene glycol alginate (WHO Food Additives Series 5)
       Propylene glycol alginate (WHO Food Additives Series 32)