INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
WORLD HEALTH ORGANIZATION
TOXICOLOGICAL EVALUATION OF SOME
FOOD COLOURS, ENZYMES, FLAVOUR
ENHANCERS, THICKENING AGENTS, AND
CERTAIN FOOD ADDITIVES
WHO FOOD ADDITIVES SERIES 6
The evaluations contained in this publication were prepared by the
Joint FAO/WHO Expert Committee on Food Additives which met in Rome,
4-13 June 19741
World Health Organization Geneva 1975
1 Eighteenth Report of the Joint FAO/WHO Expert Committee on
Food Additives, Wld Hlth Org. techn. Rep. Ser., 1974, No. 557.
FAO Nutrition Meetings Report Series, 1974, No. 54.
DIMETHYLPOLYSILOXANE
Explanation
This compound has been evaluated for acceptable daily intake by
the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1,
Ref. No. 20) in 1969.
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
Some silicone fluids may contain 5% silica. Data on methylphenyl
or other mixed polysiloxanes are not applicable to dimethyl
polysiloxane.
Mouse
Groups each of 12 male Buckberg mice which had been fasted
four hours received a single dose of 0.5 ml/kg bw sesame oil
containing 0 or 6 mg/kg (SiO2)x, or 0.5 ml/kg bw of Anti foam A
or 1.67 ml/kg emulsion of Antiform A, (Antiform A is a mixture of
polydimethylsiloxanes containing trimethylsilyl and blocks and
18% low molecular weight species as well as dispersed silica) or
Antifoam B (polydimethylsiloxane plus dispersed silica) or other
polydimethylsiloxanes with or without emulsifiers. Urine was removed
direct from the bladder and bile direct from the gall bladder 4, 12
and 24 hours after treatment. There were no statistically significant
differences in urinary or biliary silicon concentrations, with the
exception of the A in oil and A emulsion groups, which were higher
than controls. However, the amount present only represented a very
small percentage of that available for absorption from the gut (Dow
Corning Corp., 1974).
Monkey
Three rhesus monkeys maintained in metabolic chambers were
administered a single dose of 14C-labelled polydimethylsiloxane
(prepared from randomly labelled dimethyl cyclic siloxanes), at dose
levels equivalent to 1.15, 13.7 and 18.0 mg/kg bw. Approximately 0.5
to 0.9% of the dose was found in expired air. The half-life for
pulmonary elimination was 4-6 hours. Less than 0.1% of the dose
was lost as volatiles from urine, flatus and faecal material.
Approximately 2.0 to 2.5% of the dose was present in urine, with a
half-life of 24 hours. The bile contained 0.1 to 0.3% of the dose in
the first 24 hours post dosing. Faecal material collected over a 92
hour period contained 80-90% of the dose. Blood levels were below
detection limit (1 µg/ml).
In another study in which the C14-labelled polydimethylsiloxane
was essentially free of low molecular weight species, oral dosing at
21.8, 41.8 mg/kg bw resulted in 0.01 to 0.02% recovery of the dose in
expired air, 0.001-0.22% in urine and 93-97% in faeces. Analyses of
the silicone fraction in the faeces indicated that no chemical change
had occurred.
Analyses of 40 tissues from an animal 72 hours post dosing showed
that the total cumulative radiolabel in the tissues was less than
0.01% of the administered dose (Dow Corning Corp., 1974).
TOXICOLOGICAL STUDIES
Special studies on neurotoxicity
Rat, rabbit, monkey
Male rats, New Zealand white rabbits and female cynomolgus
monkeys were injected spinally with dimethylpolysiloxane fluid (Dow
Corning MF 360). The test animals were sacrificed 30 or 90 days after
injection. There was no evidence of neurological effect. At autopsy,
none of the test rabbits or monkeys showed any significant
pathological change in any of the nervous tissues. Changes observed in
the nervous tissue of rabbits were as frequent in controls (treated
with saline) as in test animals (Hine et al., 1969).
Rats were injected intraperitoneally with 14-C labelled
dimethyl-polysiloxane. Twenty-five days after dosing, 96.52% of the
dose was in the tissues. None was found in accumulated urine and
faeces samples. Most of the activity was distributed in the fat
(51.0%). The liver contained 13.5-16.1% of the activity, presumably in
the fat. None was present in heart or blood. C14-labelled silicone
was administered to rats by intracisternal injection, and tissue
distribution studied 45 days after dosing. Approximately 92% of the
administered activity was recovered in the tissues. The largest
fraction was present in the brain, vertebral column and spinal cord,
41.1, 31.4 and 9.9% respectively, 10% or less was present in the fat,
and traces of the C14 label were present in the spleen, liver and
lungs. There was no evidence of demethylation (Hine et al., 1969).
Acute toxicity
LD100
Animal Route mg/kg bw Reference
Rat s.c. >5 000 Frazer, 1959
" i.m. >5 000 "
" i.p. >5 000 "
Rabbit s.c. >5 000 "
" i.m. >5 000 "
" i.p. >5 000 "
Parenteral administration produced no significant gross or
histopathological abnormalities nor was any silicate found in the
urine of rats or rabbits (Frazer, 1959). Transient conjunctival
irritation has been noted both in rabbits and man for 24-48 hours
after contact (Child et al., 1951).
The data on acute toxicity vary with the viscosity and are
generally i.p. rat > 10 ml/kg bw (Rowe et al., 1948). Only
hexamethyldisiloxane and dodecamethylpentasiloxane appeared to be
toxic in acute tests and irritant on intradermal or subcutaneous
application to rabbits. For all the silicones on test 20 percutaneous
applications for one month produced no adverse effects (Rowe et al.,
1948).
Short-term studies
Rat
Four groups of five female rats each were fed diet containing 0%
and 0.1% silicone for three months. No adverse effects were noted on
general condition, body weight, growth rate, blood urea levels and
organ weights. The histopathology of major organs was normal (Child et
al., 1951).
Groups of five female adult rats received 20 doses of 0, 1.0,
2.0, 5.0, 10.0 and 20.0 g/kg bw of silicone fluid (350 cSt) over 28
days without deleterious effects on growth, haematology, organ weights
and histopathology (Rowe et al., 1948).
Silicone fluids of viscosity 50, 350, 1000, 10 000, 60 000 cSt
were fed for 90 days to five groups of 10 male and 10 female rats at a
level of 1% in their diet. Twenty males and 20 females were controls.
No significant adverse effects were noted on mortality and food
consumption, body weight, haematological indices, organ weights and
histopathology (MacDonald et al., 1960).
Two groups of 15 rats received dimethylpolysiloxane (DC151) at
0.3 and 1.0% of their diet with 10 rats acting as controls. Food
consumption, haematology and mortality experience were similar for
test and control groups. There was slight depression of body weight in
the group receiving the highest dietary level (Pollard, 1960).
Groups of five male and five female rats were fed a diet
containing 1% silicone fluids of viscosity 50 and 350 cSt for one
year. Controls consisted of 10 male and 10 female rats. No adverse
effects were noted upon body weight, haematology, blood urea,
nitrogen, SGPT, cholesterol, serum alkaline phosphates, urinalysis,
organ weights. Histological findings in major organs were normal
(Carson et al., 1966).
A group of 10 rats (five male and five female) was fed a mixture
(96% liquid dimethylpolysiloxane and 4% silica aerogel) in the diet at
a level of 1% for one year. Ten male and 10 female rats served as
control. No significant differences were found between the test and
the control animals in growth, body weight, haematology, blood urea,
urine analysis, serum pyruvic transaminase activity, organ weight
(10 organs) and histopathology (13 organs) (Carson et al., 1966).
Three groups of five male and five female rats were maintained
for approximately 260 days on diets containing 0.0%, 0.5% and 2% of a
silicone emulsion consisting of 50% Antifoam A (silicon eith silica)
with 2% pentaerythritol distearate as the emulsifying agent. No
adverse effects were noted on body weight and organ weights. Blood
remained normal and no abnormal amounts of protein were seen on
reproduction as measured by mating to produce and wean single sets of
offspring in each group (Frodsham, 1956).
Rabbit
In a similar experiment the same mixture was fed to a group of
six rabbits (three male and three female) at a level of 1% in the diet
for eight months. Six male and six female rabbits served as control.
No significant differences were found between the test and the control
animals in any of the parameters listed in the rat study (Carson,
1966).
Groups of three male and three female rabbits were fed diets
containing 1% silicone fluids of viscosity 50 and 350 cSt for eight
months. Controls consisted of six male and six female rabbits. No
adverse effects were noted upon body weight, haematology, blood urea,
nitrogen, SGPT, cholesterol, serum alkaline phosphatase, urinalysis,
organ weights. Histological findings on major organs were normal
(Carson et al., 1966).
Dog
Groups of two adult dogs were each fed doses of 0, 300, 1000 or
3000 mg/kg bw silicone fluid five days each week for six months. Apart
from moist and frequent loose stools in test dogs no abnormal effect
on body weight was noted. Small amounts of silicone could be recovered
from the faeces of the group fed 3000 mg/kg bw. Haematology and
urinalysis gave no abnormal findings. Gross and histopathology
revealed nothing abnormal. The liver of all dogs fed silicone fluid
but not of controls presented brown/black deposits of iron-free bile
in the Kupffer cells and parenchyma, the quantities being directly
related to the silicone dose administered. Similar deposits were also
found in the interlobular bile ducts of dogs fed the highest dose. The
significance of these observations remains unexplained (Child et al.,
1951).
Two adult male dogs received daily 1.0 and 313 g/kg bw
dimethylpolysiloxane (DC151) in divided doses for eight months. No
abnormalities were detected regarding behaviour, body weight,
haematology and urinalysis. Monthly biopsies of liver, spleen, kidney
and bone marrow were normal in all respects (Pollard, 1960).
Monkey
Two groups of two monkeys were fed dimethylpolysiloxane (DC151)
five days a week for eight months either 100 or 300 g/day. One monkey
was used as control. All monkeys exhibited occasional diarrhoea. No
other abnormalities were observed (Pollard, 1960).
Long-term studies
Rat
Groups of 25 male and 25 female rats were kept on a diet
containing 0% or 0.3% silicone fluid for two years. There was no
difference between tests and controls regarding appearance, growth,
survival or morbidity, haematology, blood urea, liver lipids, organ
weights, macroscopic and microscopic pathology (Rowe et al., 1950). In
another study three groups of 30 female and 10 male rats were fed a
diet containing 0%, 0.01% and 0.1% silicone fluid and observed for two
years. Two further generations were reared and fed the same diets. The
F1 generation was autopsied at 28 weeks, the F2 generation at 25
weeks. There were no consistent adverse effects as regards body
weights, gross and histopathology. The consistent slight weight
increase of the small gut was not statistically significant. No silica
was found in the gut wall or any undue rise in other organs. Tumoric
incidence was not abnormal. Liver function tests, urinalysis, fat
absorption, renal function tests and haematology were not remarkable
for F1 and F2 tests and controls (Frazer, 1959).
Two groups of 10 weanling rats were kept on a diet containing 0%
and 0.1% silicone fluid for two years. There was no consistent adverse
effect as regards body weight, behaviour and histopathology (Gloxhuber
& Hecht, 1955).
OBSERVATIONS IN MAN
Preparations containing dimethylpolysiloxane have been used
therapeutically in man to reduce foaming during gastroscopy and as
anti-flatulence treatment at doses of up to 200 mg/day (Dailly &
Rider, 1954; Garry, 1956; Oswald, 1961; Hock, 1962; Entine, 1962;
Reinhardt, 1961). Twenty-seven patients received 48 ml
dimethylpolysiloxane (DC151) in divided doses for 3-13 months without
significant toxic effects except occasional nausea (Pollard, 1960).
Polydimethylsiloxanes A and M compounds either in sesame oil or
emulsified were administered orally in single doses (100 mg/kg or
30 mg/kg solids for emulsions) to humans under conditions of
controlled dietary and fluid intake. Administration of the test
compound M did not result in a statistically significant increase in
total or organosoluble urinary silicon eliminated in the 72 hours
following administration of the test compound. This compound does not
contain low M.W. polymers. Administration of compound A, which
contains low M.W. polymers, resulted in increased urinary output of
silicon and organosoluble urinary silicon during the 72 hour post
dosing period. 1.8-3.3% of the administered dose was excreted in the
urine. About 25% of this was in the form of a soluble organosilicon
compound that has not been identified.
Examination of expired air indicated no organosilicon compounds
were exhaled by individuals receiving compound M. In the case of
compound A, approximately 0.35% of the dose was exhaled in the eight-
hour post dosing period. The exhaled material contained principally
octamethylcyclotetrasiloxane and a small amount of
decamethylcyclopentasiloxane (Anonymous, 1974).
Comments:
Studies have been carried out on silicone fluids with and
without the addition of silica. The presence of silica did not
raise any toxicological problems nor did it affect the results
of the experiment in a significant way. Short-term studies have
been carried out in several species, including one study on an
emulsion of dimethylpolysiloxane. An adequate long-term study with
dimethylpolysiloxane has been carried out in the rat. None of these
studies has revealed any significant toxicity. The metabolic studies,
including those in man, indicate that the orally administered
dimethylsiloxanes are mainly excreted unchanged in the faeces. The
provision of this data meets the requirements of the committee for
metabolic studies.
EVALUATION
Level causing no toxicological effect
Rat: 0.1% (= 1000 ppm) in the diet equivalent to 150 mg/kg bw
Estimate of acceptable daily intake for man
0-1.5 mg/kg bw
REFERENCES
Anonymous (1974) Report No. 4244 from Dow Corning Corp., Sines 10030
Project No. 0831
Carson, S., Weinberg, M. S. & Oser, B. L. (1966) Proceedings of the
Scientific Section of the Toilet Goods Association, No. 45, 8-19
Child, G. P., Paquin, H. O., jr & Deichmann, W. B. (1951) Arch.
industr. Hyg., 3, 479
Dailly, M. E. & Rider, J. A. (1954) J.A.M.A., 155, 859
Entine, J. H. (1962) J. Abdom. Eng., 4, 123
Frazer, A. C. (1959) Unpublished report dated November
Frodsham, J. (1956) Unpublished report No. IHR/63, Imperial Chemical
Industries Ltd., Industrial Hygiene Research Laboratories
Garry, M. W. (1956) Amer. J. Gastroent., 25, 733
Gloxhuber, C. & Hecht, G. (1955) Arzneimittel. Forsch., 5, 10
Hine, C. H. et al. (1969) Tox. App. Pharm., 15, 566
Hode, C. W. (1962) Med. Times, 90
MacDonald, W. E., Lainer, G. E. & Deichmann, W. B. (1960) Arch.
industr. Hyg., 21, 514
Oswald, W. J. (1961) Curr. Ther. Res., 3, 443
Paul, J. & Pover, W. F. R. (1960) Brit. J. industr, Med., 17, 149
Pollard, H. M. (1960) Unpublished report supplied by Dow Corning Co.
Reinhardt, W. I. (1961) Med. Times, 89, 1099
Rowe, V. K., Spencer, H. C. & Bass, S. L. (1948) J. industr. Hyg., 30,
332
Rowe, V. K., Spencer, H. C. & Bass, S. L. (1950) Arch. industr. Hyg.,
1, 539