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.



         These substances have been evaluated for acceptable daily intake
    by the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1,
    Ref. No. 27) in 1971.

         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.



         Groups of five male and five female rats received in their diet
    either 20% soybean oil or thermally oxidized material. Highly modified
    material reduced the absorption of dietary fat in proportion to the
    degree of modification introduced. Modified material delays absorption
    of oil from the gastrointestinal tract as measured by residuals found
    in the gut. Similar delaying effects have been demonstrated on the
    presence of chylomicrons and fat in the intestinal lymph fluid. The
    passage of intestinal contents is delayed if modified oil is
    administered. Compared with normal oil there is an early increase
    followed by only slight decrease in bile flow following oral
    administration of modified oil. Intraperitoneal administration of
    modified oil increases the diuretic effect of normal soybean oil when
    given intraperitoneally. Study of the liver function after eight weeks
    feeding of modified oil showed retention of the bromosulphophthalein
    used as indicator compared with normal oil (Kieckebusch et al., 1962).
    The in vitro effect of modified oil on the kinetics of various
    cellular enzyme systems showed generally no inhibition of oxidative
    metabolism (Kieckebusch et al., 1962).


    Acute toxicity

         None available.


    *    It should be noted that some of the studies refer to the
    unesterified thermally oxidized oils.

    Short-term studies


         Groups of 20 male and 20 female rats received over 12 to 16 weeks
    in their diet either 20% untreated soybean oil of 5% variously
    modified soybean oil plus 15% olive oil or 2.5% modified oil plus
    17.5% olive oil. Only highly modified oils showed significant
    reduction in growth, food intake and increased mortality. No definite
    effect was noted at the 2.5% level. Motor activity of animals on high
    doses of highly modified oil was increased compared with controls. The
    weights of major organs were similarly increased for the groups on the
    more highly modified oils. Gross and histopathology showed some
    pathological changes in the thyroid and kidney of the group receiving
    the most highly modified material (Kieckebusch et al., 1962).

         Three groups each of six rats were treated for 17 weeks with an
    esterified product at 0, 0.084 and 0.84% of their basic diet. There
    was no significant effect on weight gain and macroscopic appearance.
    Liver and stomach were examined histologically and found to be normal
    (Dam, 1952).

         Two groups of nine male rats received for 36 weeks feeds
    containing margarine made with an esterified product at 0.3 and 3%
    levels. No controls were used. No weight differences or gross
    pathological changes were noted. The histology of kidneys, liver and
    small intestine was normal (Aaes-Jorgensen et al., 1954).


         Four groups of four female pigs received an esterified product
    for 98 days at dietary levels of 0, 0.4, 2 and 10%. No significant
    effects were discovered on growth rate, food consumption, blood
    picture, liver and kidney function, serum chemistry, organ weights,
    gross and histopathology due to administration of the test compound
    (Gyrd-Hansen & Rasmussen, 1968).

    Long-term studies


         A three generation study was performed using an average level
    of 15% esterified product in the diet. The P generation (57 females,
    15 males) was observed for at least 24 months. Growth, body weight
    gain and appearance were similar to controls (seven male, seven
    female) receiving 15% soybean oil. Five animals in the test group
    developed tumours but none in the control group. There were 16
    survivors in the test group and two in the control group.

         The F1 generation (37 male, 37 female) was also observed for 24
    months. Thirty-seven males and females received soybean oil as
    controls. Twenty-four test and 10 control animals survived two years.
    Two test-animals and three controls developed tumours. The F2
    generation (57 female, 27 male) was observed for over two years.
    Seventy males and females acted as controls on soybean oil. Four test
    and 19 control animals survived 24 months. No animal in the test group
    but three in the control group developed tumours. Both the F1 and F2
    generation showed no significant differences from controls as regards
    growth, body weight gain, gross and histopathology.

         In another experiment an esterified product was fed orally at the
    rate of 3 g/day and injected s.c. to 29 rats at 1 ml weekly for five
    months and 2 ml bi-weekly for a further three months. Animals were
    observed for 27 months. No tumours developed. A control series of 30
    rats treated similarly with oral esterified product and injected s.c.
    with refined soybean oil showed four tumours after 24 months
    observation, none at the site of injection. The F1 test generation
    (nine male, nine female) received 3 g esterified product orally and
    1 ml i.p. for eight weeks, followed by a further 1 ml i.p. for four
    months. After 11 months six survived without any tumours being noted.
    The control group (14 male, four female) received 1 ml soybean oil
    s.c. for five months and 2 ml s.c. for three months. During 29 months
    observation, one rat developed a tumour at the site of injection
    (Harmsen, 1959, 1960, 1961).

         Rats fed with 20% of thermally oxidized soybean oil in the diet
    had a significantly longer life-span (807  32 days) than those fed
    with 20% of fresh soybean oil (673  42 (mean  S.E.)): a similar
    difference was observed between other oxidized and fresh fats and oils
    (Kaunitz et al., 1966).


         No adequate specification has been provided for this material. It
    has not been possible to relate the available toxicological
    information to the materials in commercial use.


         Not possible on the data provided.


    *    Previously allocated ADI is withdrawn.


    Aaes-Jorgensen, E. et al. (1954) Unpublished report supplied by
         Grindstedvaerket Laboratoriet

    Dam, H. (1952) Unpublished report submitted by Grindstedvaerket

    Gyrd-Hansen, N. & Rasmussen, F. (1968) Fd. Cosmet. Toxicol., 6, 163

    Harmsen, H. (1959) Unpublished report submitted by Grindstedvaerket

    Harmsen, H. (1960) Unpublished report submitted by Grindstedvaerket

    Harmsen, H. (1961) Unpublished report submitted by Grindstedvaerket

    Kaunitz, H., Johnson, R. E. & Pegus, L. (1966) Proc. Soc. exptl. Biol.
         Med., 123, 204

    Kieckebusch, K. et al. (1962) Fette, Seifen, Anstrichmittel, 64, 1154

    See Also:
       Toxicological Abbreviations