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    FAO Nutrition Meetings 
    Report Series No. 48A 
    WHO/FOOD ADD/70.39




    TOXICOLOGICAL EVALUATION OF SOME
    EXTRACTION SOLVENTS AND CERTAIN 
    OTHER SUBSTANCES




    The content of this document is the 
    result of the deliberations of the Joint 
    FAO/WHO Expert Committee on Food Additives 
    which met in Geneva, 24 June  -2 July 19701




    Food and Agriculture Organization of the United Nations
    World Health Organization


                   

    1 Fourteenth 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.


    FOOD-GRADE MINERAL OIL

    Biological data

    Biological aspects

         Mineral oils are of variable composition depending on the boiling
    point of the fractions used. For food purposes usually liquid
    petrolatum or liquid paraffin are employed which consist essentially
    of n-alkanes and some cyclic paraffins. They are chemically inert
    especially as regards the straight chain alkanes and on ingestion most
    of the mineral oil (98%) remains unabsorbed in the faeces. There is
    evidence now that small amounts of mineral oil (2%) are absorbed as
    such by the intestinal mucosa and are distributed throughout the body.
    A very small fraction may undergo further biochemical transformation.
    Sources of mineral oil are laxatives or oils used in food technology
    as release agents or for lubrication purposes (Boitnott and Margolis,
    1966).

         Oil droplets, identified as saturated alkane hydrocarbons, have
    been demonstrated in mesenteric lymphnodes and nodes of the porta
    hepatis in man. Similar droplets have been identified in human liver,
    spleen and adipose tissue. The small amounts formed are consistent
    with the calculated intake from food use (47.5 g per head per year in
    the US). No known harm appears associated with these residues
    (Boitnott and Margolis, 1966).

         Similar deposition of oil and minor absorption was demonstrated
    in rabbits, rats and guinea-pigs fed liquid petroleum for 7 months or
    more. Histochemical evidence showed absorption to be proportionate to
    length of exposure. The mechanism of absorption was unknown but the
    absorbed particles showed evidence of foreign body reaction and
    phagocytic ingestion (Stryker, 1941).

         Mineral oil used as emulsifying medium for s.c. injection was
    transported from the site of injection without causing any systemic
    effects (Brown, 1966).

         H3-labelled mineral oil was administered to rats orally and
    i.p., 5 hours after oral dosing with 0.66 mg/kg bodyweight it could be
    shown that over 80% was not absorbed but excreted in the faeces, 1-5%
    was absorbed unchanged and another 15% appeared in carcass as H3
    non-mineral oil substance. Some H3 had exchanged with available H and
    possibly some mineral oil had been modified metabolically.
    Radioactivity was found principally in liver, fat, kidney, brain, and
    spleen. Following i.p. administration there was only very slow
    excretion. 11% appeared in the faeces during 8 days and only traces in
    the urine (Ebert et al., 1966).

         Mineral oil passes through the gut wall unchanged and more is
    absorbed in the presence of powerful emulsifiers, provided that the
    particle size of the emulsion is about 0.5µ (Frazer et al., 1944).
    Prolonged administration of 0.66 ml/kg for 31 days had no effect on
    the amount absorbed when compared with single dosing (Ebert et al.,
    1966).

         A wide range of fractions of mineral oil contain carcinogenic
    compounds especially higher boiling fractions of the range 300° - 350°
    - 400°C as shown by skin painting of mice and rabbits (Cook et al.,
    1958) but refined material may be free from these carcinogenic
    constituents (Prigal, 1967). Inoculation of 64 mice with a combination
    of mineral oil and killed staphylococci induced plasma cell tumours in
    7 animals (Potter and Robertson, 1961), Later experiments produced
    similar results with mineral oil alone (Potter and Boyce, 1962). Some
    doubts have been raised as to the probable role of virus in production
    of these mouse plasma cell tumours (Prigal, 1967). No human cancer has
    been reported following many years of oleothorax use (Prigal, 1967).

    Short-term studies

    Rat: 10 rats were each fed a total of 17 g liquid paraffin in 18 g
    olive oil over 16 days mixed into their normal diet. Some 65% was
    absorbed as estimated free faecal loss. Another 5 rats received over
    28 days a total of 28 g liquid paraffin in their diet. Only 9% was
    absorbed. Lymph collected during absorption from intestinal lymphatics
    showed that absorbed paraffin had been metabolically modified. (Daniel
    et al., 1953).

    Long-term studies

    Mouse: 2 groups of 30 mice had mineral oil applied to their skin 3
    times weekly at 15 mg/application for 311 and 478 days respectively.
    No tumours were found (Esso Research, 1960).

    Rat: Animals were kept for 15 months on diets supplemented with 10%
    liquid paraffin. The liver contained 0.4% dry weight liquid paraffin.
    Some active metabolism may occur but liver function was not affected.
    (Daniel et al., 1953). In another experiment 2% mineral oil was fed in
    the diet to 30 rats for 500 days without adverse effects (Schmäghl and
    Reiter, 1953).

    Nutritional implications

         There are two possible reasons for the presence of mineral oil in
    food; (1) in trace amounts from its use as a lubricant or separant
    e.g. in tin greasing before baking, or from traces on the surface of
    knives used to cut dough in breadmaking, or as a coating e.g. of
    fruit; (2) as a substitute for fat either because it is cheaper or in
    slimming foods. The maximum daily intake is calculated to be about 100
    mg of which some 80 mg are contributed from its use on the machinery
    in the baking industry (Council on White Mineral Oil, 1961).

         There has been a great deal of work on the effect of mineral oil
    in impeding the absorption of fat soluble vitamins A (and precursors)
    D, E, K and essential fatty acids. There is no doubt that interference
    with absorption can occur, particularly of carotene if amounts in food
    exceed approximately 6000 ppm (Steigmann et al., 1952). Whether the
    amounts likely to appear in the food of children are of clinical
    importance is much less certain (assuming that it is not used as an
    ingredient as in (2) above). But the diets of many of these may
    contain amounts of these vitamins that are in any case marginal or
    inadequate and there seems no reason for the inclusion of mineral oil
    in foods which are specifically intended for infants with the possible
    exception of rusks (concerning which enquiries are being made which
    will be later reported as they may be subject to the same
    contaminating processes as bread).

    Comments

         The use of food grade mineral oil is self-limiting because of its
    laxative effect. Although a small percentage of ingested mineral oil
    is absorbed as such and deposited in various organs it is without any
    apparent harm. Most of the ingested material is not absorbed but is
    excreted in the faeces. Apart from the nutritional implications in
    relation to the intake of fat soluble vitamins, there are no
    toxicological problems arising from the use of food grade mineral oil.

    Evaluation

         There appears to be no need to set a limit in food beyond that of
    good manufacturing practice.

    REFERENCES

    Boitnott, J. K. & Margolis, S. (1966) Bull. Johns Hopk. Hosp., 118,
    414

    Brown, E. A. (1966) Review of Allergy, 20, 148 & 235

    Cook, J. W., Carruthers, W. & Woodhouse, D. L. (1958) Brit. med.
    Bull., 14, 132

    Council on White Mineral oil (1961) Food Additive Petition 302 to US
    Food and Drug Administration dated 21/2/1961

    Daniel, J. W. et al. (1953) Biochem. 1., 54, 37

    Ebert, A. G., Schleifer, C. R. & Hess, S. M. (1966) J. Pharmac.
    Sci., 55, 923

    Esso Research (1960) Unpublished report submitted to WHO

    Frazer, A. C.  Schulman, J. H. & Stewart, H. C. (1944) J. Physiol.,
    103, 306

    Potter, M. & Boyce, C. R. (1962) Nature, 193, 1086

    Potter, M. & Robertson, J. (1961) J. nat. Cancer Inst., 25, 847

    Prigal, S. J. (1967) Annals of Allergy, 25, 449

    Schmähl, D. & Reiter, A. (1953) Arzneimittel-Forsch., 3, 403

    Steigmann  F. et al. (1952) Gastroent., 20, 587

    Stryker, W. A. (1941) Arch. Pathol., 31, 670
    


    See Also:
       Toxicological Abbreviations
       Food-grade mineral oil (WHO Food Additives Series 5)