TOXICOLOGICAL EVALUATION OF CERTAIN FOOD ADDITIVES
WHO FOOD ADDITIVES SERIES 10
The evaluations contained in this document were prepared by the
Joint FAO/WHO Expert Committee on Food Additives*
Rome, 21-29 April 1976
Food and Agriculture Organization of the United Nations
World Health Organization
*Twentieth Report of the Joint FAO/WHO Expert Committee on Food
Additives, Geneva, 1976, WHO Technical Report Series No. 599, FAO Food
and Nutrition Series No. 1.
MINERAL OIL (FOOD GRADE)
Explanation
This substance has been evaluated for acceptable daily intake for
man by the Joint FAO/WHO Expert Committee on Food Additives in 1970
and 1973 (see Annex I, Ref. 23, p. 39; Ref. 33, p. 417).
Since the previous evaluation, additional data have become
available and are summarized and discussed in the following monograph.
The previously published monographs have been expanded and are
reproduced in their entirety below.
BIOLOGICAL DATA
General aspects
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 (Fiero, 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 inquiries are being
made which will be later reported as they may be subject to the same
contaminating processes as bread).
BIOCHEMICAL ASPECTS
Absorption, distribution and excretion
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 & 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 per head per year in
the United States of America). The quantities of extractable oil and
types of histological appearance have been reported (Boitnott &
Margolis, 1970). There is no correlation with age or sex (Kelsall &
Blackwell, 1969). There is an unusual geographical incidence, being
about 50% in North America and 10% in Western Europe and in post
mortem examinations (Cruikshank, 1972). No known harm appears
associated with these residues (Boitnott & Margolis, 1966).
Similar deposition of oil and minor absorption was demonstrated
in rabbits, rats and guinea-pigs fed liquid petrolatum for seven
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).
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 0.5 µ (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).
In studies on absorption of aliphatic hydrocarbons in the rat
(Albro & Fishbein, 1970) simple mixtures of these compounds were
administered by gastric intubation at dose levels of up to 500 mg/kg.
The percentage retention of the aliphatic hydrocarbons was inversely
proportional to the number of carbon atoms and ranged from 60% for
C14 to 5% for C28 compounds. The major site of absorption was found
to be the small intestine.
Metabolism
H3-labelled mineral oil was administered to rats orally and i.p.
five hours after oral dosing with 0.66 mg/kg bw 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 eight days and only
traces in the urine (Ebert et al., 1966).
Administration of 14C-labelled octadecane to cattle indicated
that while some of the label was incorporated into the lipids of the
rumen bacteria and the lipid portion of the blood and the body fat,
most of the octadecane was eliminated in the faeces (Bartley et al.,
1971). Studies in which straight chain hydrocarbons (C14 to C17) were
incorporated into the diet of poultry indicated that this species was
capable of absorbing and utilizing the energy from this material
(Squibb and Frankenfeld, 1972).
TOXICOLOGICAL STUDIES
Special studies on carcinogenicity
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
seven animals (Potter & Robertson, 1961).
Mouse
A group of 36 DBA/2 and 12 CBA female mice were given a total of
1.5 ml of Primol D mineral oil in three i.p. injections over a 15-week
period (Rask-Nielsen & Ebbesen, 1965). The survivors were killed at 24
months of age. Small intraperitoneal granulomatous nodules containing
oil droplets developed in all mice. 42% of the DBA/2 mice developed
reticulosarcomatous growths (Dunn type A) in some of the peritoneal
nodules. Leukemic infiltrations of varying degree of severity were
found in the livers of several mice and less frequently in other
organs. However, only one of the CBA mice developed a reticulum cell
sarcoma. In contrast, BALB/C mice given mineral oil by i.p. injection
developed plasma cell neoplasms in the intraperitoneal nodules (Potter
& Boyce, 1962). The purity of the mineral oil samples used in these
studies is uncertain. Indeed there was some indication that the sample
used in the later study contained an impurity having physical
properties similar to those of some carcinogenic polycyclic aromatic
hydrocarbons.
Some doubts have been raised as to the probable role of virus in
production of mouse plasma cell tumours (Prigal, 1967). No human
cancer has been reported following many years of oleothorax use
(Prigal, 1967).
Short-term studies
Rat
Ten 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 from faecal loss. Another five 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).
Rabbit
Fifteen rabbits, weighing between 1.9 and 2.5 kg, were given
daily 25 ml of a mixture (1:1) of olive oil and paraffin oil (purity
not stated). The animals were sacrificed at regular intervals, after
60-406 days of treatment. At this high dosage level, from the first to
the third week, a relatively important loss of weight is noted, but
rapidly a state comparable to the controls is regained. Progressively,
the paraffin oil passes the intestinal epithelium and accumulates in
the mesenteric lymph glands, then becoming distributed in the rest of
the body, with preferential deposition in the liver and in the spleen.
Histologically, diffuse hyperplasia of reticulo endothelial cells,
somewhat similar to that seen in human Whipple's disease, is observed
(Borer, 1960).
Long-term studies
Mouse
Two groups of 30 mice had mineral oil applied to their skin three
times weekly at 15 mg/application for 311 and 478 days respectively.
No tumours were found (Anonymous, 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 (Schmähl &
Reiter, 1953).
Comments
"Mineral oils" have been demonstrated in human tissues. While no
demonstrable pathological consequences have occurred from the presence
of such oils in human tissues resulting from ingestion, its storage is
considered to be undesirable and exposure to mineral oils should be
kept to a minimum.
A recent development is the production, by hydrogenation, of oils
with chemical specifications similar to those of food grade mineral
oil. Such oils contain more cyclic paraffins since the aromatic
components are not removed before distillation but are converted to
saturated cyclic compounds. While these oils have not been shown to
contain polycyclic cromatic hydrocarbons in concentrations greater
than occur in food grade oil, there are insufficient toxicological
data and information on the similarities and differences in the
composition of the two types of oil to allow a toxicological
evaluation of the hydrogenated oil.
EVALUATION
Estimate of acceptable daily intake for man
Not specified.*
REFERENCES
Albro, P. W. & Fishbein, L. (1970) Biochim. Biophys. Acta, 219, 437
Anonymous (1960) Unpublished data submitted to the World Health
Organization by Esso Research and Engineering Co.
Bartley, E. C., Helmer, L. G. & Meyer, R.M. (1971) J. Animal Science,
33, 1351
Boitnott, J. K. & Margolis, S. (1966) Bull. Johns Hopk. Hosp., 118,
414
Boitnott, J. K. & Margolis, S. (1970) Johns Hopkins Med. J., 127, 65
Borer, F. (1960) Rev. franç. études clin. et biol., 5, 47
Brown, E. A. (1966) Review of Allergy, 20, 148 & 235
* Applies only to mineral oil not made by hydrogenation process.
Cook, J. W., Carruthers, W. & Woodhouse, D. L. (1958) Brit. med.
Bull., 14, 132
Cruikshank, B. (1972) Personal communication
Daniel, J. W. et al. (1953) Biochem. J., 54, 37
Ebert, A. G., Schleifer, C. R. & Hess, S. M. (1966) J. Pharmac. Sci.,
55, 923
Fiero, G. W. (1961) Supplement to Food Additive Petition No. 302 to
the US Food and Drug Administration date 21 February 1961.
Unpublished report from the Council on White Mineral oil
submitted to the World Health Organization by the chairman of API
Sub-committee on White Mineral Oil
Frazer, A. C., Schulman, J. H. & Stewart, H. C. (1944) J. Physiol,
103, 306
Kelsall & Blackwell (1969) Pathology, 1, 211
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
Rask-Nielsen, R. & Ebbesen, P. (1965) J. Nat. Cancer Inst., 35, 83
Schmähl, D. & Reiter, A. (1953) Arzneimittel-Forsch, 3, 403
Squibb, R. L. & Frankenfeld, J. W. (1972) Poultry Science, 51, 2056
Steigmann, F. et al. (1952) Gastroent., 20, 587
Stryker, W. A. (1941) Arch. Pathol., 31, 670
See Also:
Toxicological Abbreviations