INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
WORLD HEALTH ORGANIZATION
TOXICOLOGICAL EVALUATION OF SOME
FOOD COLOURS, EMULSIFIERS, STABILIZERS,
ANTI-CAKING AGENTS AND CERTAIN
FAO Nutrition Meetings Report Series
No. 46A WHO/FOOD ADD/70.36
The content of this document is the result of the deliberations of the
Joint FAO/WHO Expert Committee on Food Additives which met in Rome,
27 May - 4 June 19691
Food and Agriculture Organization of the United Nations
World Health Organization
1 Thirteenth 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.
PROPYLENE GLYCOL ALGINATE
In vitro hydrolysis by simulated gastric and intestinal juices shows
practically no effect of gastric juice, while intestinal juice
hydrolyses 25 per cent. of the ester in 4 h, 65 per cent. in 12 h and
80 per cent. in 24 h (McNeely & Shepherd, 1966).
No in vivo studies are available on the metabolic fate of this
ester. Alginic acid and its alginates and also the algae from which
these substances derive have been used in man for many years.
Propylene glycol is rapidly absorbed from the gut and metabolized in a
variety of ways to acetate, lactate or glycogen.
No LD50s are available. Rabbits injected intravenously,
intraperitoneally, intramuscularly or subcutaneously with 6.2 mg, 12.5
mg or 25 mg/kg body weight showed no toxic effects systemically or at
the site of injection (Steiner & MeNeely, 1951), When injected
subcutaneously or intramuscularly with up to 2 ml of sterile aqueous
two per cent. solutions of the compound no gross or histological
abnormalities occurred at the injection site. Intraperitoneal and
intravenous injections of similar amounts produced no abnormal
systemic effects (Ouer, 1949).
Of 50 human subjects known to be allergic to numerous other substances
11 showed very slight to moderate skin reactions to the intradermal
test. When five of these that showed the greatest reaction were fed
propylene glycol alginate three showed mild allergic reactions which
were duplicated in repeated tests. Of 50 non-allergic individuals
three showed very slight skin reactions, but none had reactions to
oral administration (Ouer, 1949).
1,2-Propylene glycol had a no-effect level of 2000 ppm level when
tested for embryo toxicity in the chick (Mclaughlin et al., 1965)
while 1,3-propylene glycol appeared to produce chondrodystrophy in a
high percentage of embryos (Gebhardt, 1968).
Bacteriological examination of the intestinal flora of two rats after
six months on basal diet and 21 days of five per cent. added propylene
glycol alginate showed fall in lacto-bacilli and aerobic counts with a
rise in coliforms and no change in anaerobic counts (Woodard, 1959).
Rat. Two groups of six female rats each were fed either a diet
containing 21.5 per cent. of the compound and 21.5 per cent. glucose
or a normal diet with additional 21.5 per cent. glucose for four
weeks. After sacrificing two animals in each group the remaining four
animals per group were fed a normal diet for four weeks. Thereafter
the original control group was fed a diet containing 21.5 per cent. of
the compound and the original test group was kept on control diet for
two weeks. The test group showed slight growth retardation but
appearance and behaviour remained normal. The faeces of the test group
tended to be slimy. Histopathology of intestine, kidney and liver of
the sacrificed two animals (test and controls) showed no abnormalities
Guinea-pig. Four groups of three animals each were fed a diet
containing 0 per cent., 5 per cent., 10 per cent. and 15 per cent. of
the compound for 26 weeks. No adverse effects on weight gain, food
intake, were seen and histopathology of various organs demonstrated no
significant lesions (Nilson & Wagner, 1951).
Cat. Eight cats and one control were fed a diet with 0 per cent., 5
per cent., 10 per cent. and 15 per cent. of the compound for 88-100
days. At dietary levels from 10 per cent. upwards animals showed
frequent soft stools. No signs of toxicity were noted, autopsy and
histopathology revealed nothing of significance (Nilson & Wagner,
Dog. Three groups of three male and three female beagles were fed
diets containing 0 per cent., 5 per cent. and 15 per cent. of the
compound for one year. All groups showed normal weight gains, food
consumption, haemograms, blood urea nitrogen, serum alkaline
phosphatase, blood glucose and urinalysis. A complete
histopathological examination showed no significant lesions (Woodard,
Chick. Four groups of 13-day-old chicks were fed on a diet
containing 0 per cent., 5 per cent., 10 per cent. and 15 per cent. of
the compound for three to seven weeks. All levels showed reduced
growth rate due to difficulty with the diet but no evidence of toxic
effects. Histopathology showed slight evidence of transient reversible
tissue changes in all groups (Nilson & Wagner, 1951).
Mouse. Four groups of mice were kept on diets containing 0 per
cent., 5 per cent., 10 per cent. and 25 per cent. of the compound for
12 months. At the higher levels (10 per cent.) mortality was increased
and weight gain as well as food intake reduced but histopathology was
unremarkable (Nilson & Wagner, 1951).
Rat. Four groups of 10 male and female rats were fed over their life
span diets containing 0 per cent., 5 per cent., 15 per cent. and 25
per cent. propylene glycol alginate. A fifth group received 15 per
cent. of the compound in a different basal diet. Life expectancy was
slightly reduced at the 15 per cent. and 25 per cent. level. The bulky
diet caused loose faeces. The group on 15 per cent. in a different
basal diet had normal faeces and was sacrificed at 37 weeks. No
adverse effects on weight gain, food or water consumption were noted.
Histology showed no lesions attributable to the compound (Nilson &
Wagner, 1951). Forty male and 40 female rats (P generation) were kept
on a diet containing 0 per cent. and 5 per cent. of the compound for
two years. After four to five months feeding some animals were mated.
The F1 generation was fed on similar diets, mated after four months.
and the F2 generation also kept on similar diets. At the end of two
years the survival rates were 67 per cent. male and 78 per cent.
female in test groups and 56 per cent. and 50 per cent. in the
respective control groups. The P generation survived 761 days, the
F1 and F2 generations were sacrificed at 202 and 212 days
respectively. No difference from the controls was noted regarding mean
body weight, general condition, mortality, fertility, lactation and
survival of the three generations. Haematology and blood picture were
normal, gross and histopathology showed nothing significant (Morgan.
Long-term studies in two species are available although the mouse
study extends over only 12 months. In vivo metabolic studies are in
progress to elucidate the reason for the delayed breakdown observed in
the gastro-intestinal tract.
Level causing no significant toxicological effects in the rat
Five per cent. (= 50 000 ppm) In the diet equivalent to 2500 mg/kg
Estimate of acceptable daily intake for man
mg/kg body weight
Temporary acceptance 0-12.5
Further work required by June 1972
Submission of the results of in vivo metabolic studies.
Gebhardt D. O. E. (1968 Teratology, 1, 153
McLaughlin et al. (1965) Toxicol. appl. Pharmacol., 7, 491
McNeely, W. H. & Shepherd, V. M. (1966) Report to Kelco Co. Labs,
dated 15 September 1966
Medical Research Council Laboratories (1951) Unpublished report
Morgen, F. C., cited in Woodard, G. (1959) Unpublished report
Nilson. H. W. & Wagner, J. A. (1951) Proc. Soc. exp, Biol. (N.Y.)
Ouer, R. A. (1949) Ann. Allergy, 7, 681
Steiner, A. B. & McNeely, W. H. (1951) Ind. Eng. Chem., 13, 2073
Woodard, G. (1959) Unpublished report