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



    WHO FOOD ADDITIVES SERIES NO. 5







    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
    Geneva
    1974

              

    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.


    PROPYLENE GLYCOL ESTERS OF FATTY ACIDS

    Explanation

         These substances have been evaluated for acceptable daily intake
    by the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1,
    Ref. No. 13) in 1966.

         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.

    BIOLOGICAL DATA

    BIOCHEMICAL ASPECTS

         Pancreatic lipase hydrolyzed 70% of propylene glycol monostearate
    in vitro at 40° in 15 hours (Balls & Matlack, 1938). Similarly,
    steapsin hydrolized 70% of propylene glycol distearate (PGDS)
    in vitro at 30° in 18 hours (Long et al., 1958). The absorption,
    metabolism and hydrolysis of PGDS was studied in rats using
    isotopically labelled compounds, and found to be similar to those of
    the glyceryl stearate esters (Long et al., 1958a, 1958b).

         Metabolic studies were carried out with 14C-stearyl and
    14C-succinate labelled stearyl propylene glycol hydrogen succinate.
    The substance was hydrolyzed in vitro by rat pancreatic juice and
    bile to yield stearic acid, propylene glycol monostearate, succinic
    acid, propylene glycol mono hydrogen succinate, and propylene glycol.
    After oral administration to rats, the proportions of radioactivity
    appearing in expired CO2 corresponded closely to those obtained when
    14C-stearyl soybean oil or 14C-succinic acid were administered.
    Likewise, the proportions in urine, faeces and the carcass were
    similar. A small part of the radioactivity in urine was as propylene
    glycol hydrogen (14C)-succinate. The substance was also found in
    the urine of two men (28 and 35 years of age) who took 10 g of
    non-radioactive stearyl propylene glycol over a 48 hour period: the
    amount of the partially hydrolyzed material recovered corresponded to
    about 0.1% of that administered (King et al., 1970).

    TOXICOLOGICAL STUDIES

    Acute toxicity

         Oral toxicities studies were performed in the rat for propylene
    glycol diacetate. It was shown that propylene glycol diacetate
    possesses an LD50 of 13.53 g/kg (Smyth et al., 1941).

    Short-term studies

    Rat

         Six 21-day-old rats were fed for 40 days a diet containing 60%
    propylene glycol ester. The animals showed no adverse effect on body
    weight gain. On histological examination of the kidneys no lesions
    were observed (Lepkovsky et al., 1935).

         Rats in groups of 48 were fed for 13 weeks on diets containing 0,
    1.5, 3.36 and 7.52% of propylene glycol monostearate with mono- and
    diglycerides added to bring the total fat to 7.52%. There were no
    differences between the groups in respect of growth, relative organ
    weight (adrenals, gonads, heart, kidneys, liver, spleen, brain),
    histology, blood glucose, BUN, plasma cholesterol, plasma glutamate-
    pyruvate transaminase, haemoglobin, haematocrit, white cell count,
    white cell differential counts, clotting time or urinary analyses
    (Brandner, 1973).

         A preparation containing 50% of propylene glycol esterified with
    stearic and succinic acids (stearyl propylene glycol hydrogen
    succinate), 17% of propylene glycol monostearate and lesser amounts of
    other propylene glycol derivatives ("Succistearin") was incorporated
    in diets at 2.5, 5 and 10% levels and fed to rats (10 per group) for
    six months. It was reported that there was no evidence of gross or
    histological pathology attributable to the substance (King et al.,
    1971).

    Dogs

         A preparation named Succistearin was fed at levels of 5 and 10%
    in the diet to groups of four dogs for six months. There were no signs
    of toxicity (King et al., 1971).

    Long-term studies

         No data are available.

    Comments:

         There is evidence that the propylene glycol esters of fatty acids
    are hydrolyzed to propylene glycol and fatty acids. Evaluation is
    based on the contents of propylene glycol, for which an acceptable
    daily intake has been established.

    EVALUATION

    Estimate of acceptable daily intake for man

         0-25 mg/kg bw.*

    REFERENCES

    Balls, A. J. & Matlack, M. B. (1938) Biochem. J., 123, 679

    Brandner, J. D. (1973) Unpublished report submitted by ICI America
         Inc.

    King, W R., Michael, W. R. & Coots, R. H. (1970) Toxicol. appl.
         Pharmacol., 17, 519

    King, W. R., Michael,.W.R. & Coots, R. H. (1971) Toxicol. appl.
         Pharmacol., 18, 26

    Lepkovsky, S., Ouer, R. A. & Evans, H. M. (1935) Biochem. J., 108, 431

    Long, C. L. et al. (1958a) Arch. Biochem., 77, 428

    Long, C. L., Zeitlin, B. R. & Thiesen, R. jr (1958b) Arch. Biochem.,
         77, 440

    Smyth, H. F. jr, Seaton, J. & Fisher, L. J. (1941) Ind. Hyg. Tox.,
         23, 259-268

              

    *    Calculated as propylene glycol.

    See Also:
       Toxicological Abbreviations
       Propylene glycol esters of fatty acids (FAO Nutrition Meetings Report Series 40abc)
       PROPYLENE GLYCOL ESTERS OF FATTY ACIDS (JECFA Evaluation)