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.


    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 (McNeely & Shepherd, 1966).

    No in vivo studies are available on the metabolic fate of this
    ester. Alginic acid and its 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.

    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 systemically or at
    the site of injection (Steiner & MeNeely, 1951), When injected
    subcutaneously or intramuscularly with up to 2 ml of sterile aqueous
    two 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 five of these that showed the greatest reaction were fed
    propylene glycol alginate three showed mild allergic reactions which
    were duplicated in repeated tests. Of 50 non-allergic individuals
    three showed very slight skin reactions, but none had reactions to
    oral administration (Ouer, 1949).

    Special studies

    1,2-Propylene glycol had 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).

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

    Short-term studies

    Rat. Two groups of six 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 four
    weeks. After sacrificing two animals in each group the remaining four
    animals per group were fed a normal diet for four 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
    two 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 sacrificed two animals (test and controls) showed no abnormalities
    (MRCL, 1951).

    Guinea-pig. Four groups of three animals each were fed a diet
    containing 0 per cent., 5 per cent., 10 per cent. 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).

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

    Dog. Three groups of three male and three female beagles were fed
    diets containing 0 per cent., 5 per cent. and 15 per cent. of the
    compound for one 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,

    Chick. Four groups of 13-day-old chicks were fed on a diet
    containing 0 per cent., 5 per cent., 10 per cent. and 15 per cent. of
    the compound for three to seven weeks. All levels 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, 1951).

    Long-term studies

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

    Rat. Four groups of 10 male and female rats were fed over their life
    span diets containing 0 per cent., 5 per cent., 15 per cent. and 25
    per cent. propylene glycol alginate. A fifth group received 15 per
    cent. of the compound in a different basal diet. Life expectancy 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 (P generation) were kept
    on a diet containing 0 per cent. and 5 per cent. of the compound for
    two years. After four to five months feeding some animals were mated.
    The F1 generation was fed on similar diets, mated after four months.
    and the F2 generation also kept on similar diets. At the end of two
    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 and blood picture were
    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. In vivo metabolic studies are in
    progress to elucidate the reason for the delayed breakdown observed in
    the gastro-intestinal tract.


    Level causing no significant toxicological effects in the rat

    Five per cent. (= 50 000 ppm) In the diet equivalent to 2500 mg/kg
    body weight/day.

    Estimate of acceptable daily intake for man

                                            mg/kg body weight

    Temporary acceptance                         0-12.5

    Further work required by June 1972

    Submission of the results of in vivo metabolic studies.


    Gebhardt D. O. E. (1968 Teratology, 1, 153

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

    McNeely, W. H. & Shepherd, V. M. (1966) Report to Kelco Co. Labs,
    dated 15 September 1966

    Medical Research Council Laboratories (1951) Unpublished report

    Morgen, 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

    Steiner, A. B. & McNeely, W. H. (1951) Ind. Eng. Chem., 13, 2073

    Woodard, G. (1959) Unpublished report

    See Also:
       Toxicological Abbreviations
       Propylene glycol alginate (WHO Food Additives Series 1)
       Propylene glycol alginate (WHO Food Additives Series 5)
       Propylene glycol alginate (WHO Food Additives Series 32)