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.
PATENT BLUE V
After intravenous injection into the rat of 0.5 ml of an aqueous
solution containing 5 g per 100 ml the colour is excreted in the urine
which is coloured blue during the 12 hours following the injection.
Findings are similar in the case of man when the colour is injected
subcutaneously for the detection of peripheral lymphatic trunks and
nodes for the purpose of lymphography. (Truhaut, 1962).
Animal Route LD50 Reference
per kg body-weight
Mouse oral > 3.0 g Truhaut, 1962
Mouse i.v. 1.2 g "
Rat oral > 5.0 g "
Rat i.v. 5.0 g "
The dye (as the Ca salt) had slight surface activity. The Na salt had
considerable surface activity. Protein binding and lipophilic activity
were negligible for both salts. The authors conclude that the
difference in surface activity explains the difference in the local
reactions to the two salts (Cangolli et al., 1967).
Rat. Subcutaneous injections of 1 ml of 0.8 per cent. aqueous
solution twice weekly for five weeks produced only slight tissue
reactions (Grasso & Goldberg, 1966).
Cat. Three cats were given daily a five per cent. aqueous solution
of the colour orally doses of 0.25, 0.50 and 0.75 g. No abnormalities
were found (Truhaut, 1962).
Rat. Sixty rats, half males and half females, were given in their
diet 10 000 ppm of the colour for their life-span. The used colour
was pure (no impurities were found by paperchromatography studies).
The average life-span of treated animals was 24 months and the last
animal died at an age of 37 months, two weeks. The average intake of
the colour was approximately 8O g. Forty animals were used as
controls.The average life-span of these animals was 22 months, two
weeks. For the second experiment 30 rats, half males and half females,
were given the same diet with 10 000 ppm and also for 15-19 months
once a week a subcutaneous injection of 1 ml of a one per cent.
aqueous solution. The average life-span of the animals was 18 months.
The last animal died at an age of 30 months. Twenty-six rats were used
as controls and were given 1 ml of distilled water subcutaneously for
the same period as the treated animals. The average life-span of these
animals was 19 months.
In both experiments it was found that growth, blood composition,
reproduction and the three generations of animals which were bred were
not influenced. Also, no abnormal histopathological findings or
sarcomas at the site of injection were observed (Truhaut, 1962).
Information on the metabolism of the colour is lacking. Long-term and
reproduction studies in the rat did not reveal any significant
toxicological effects. However, the corresponding sodium salt which is
not used as food colour showed evidence of considerable surface
activity on subcutaneous injection and for this reason a long-term
study in a second species is required.
Level causing no toxicological effects in the rat
One per cent. (= 10 000 ppm) in the diet equivalent to 500 mg/kg body
Estimate of daily acceptable intake for man
mg/kg body weight
Temporary acceptance 0 - 1
Further work required by June 1974
Metabolic studies in several species, preferably including man, two
year studies in non-rodent mammalian species and long-term studies in
a second species.
Gangolli, S. D., Grasso, P. & Go1dberg, L. (1967) Fd. Cosmet.
Toxicol., 5, 601
Grasso, P. & Goldberg, L. (1966) Fd. Cosmet. Toxicol., 4, 269
Truhaut, R. (1962) Aliment. et Vie, 50, 77