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.
PATENT BLUE V
This compound has been evaluated for acceptable daily intake by
the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1,
Refs Nos 10 and 20) in 1964 and 1969.
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.
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).
Special studies on surface activity
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).
Animal Route LD50 Reference
per kg bw
Mouse Oral > 3.0 g Truhaut, 1962
Mouse i.v. 1.2 g "
Rat Oral > 5.0 g "
Rat i.v. 5.0 g "
Subcutaneous injections of 1 ml of 0.8% aqueous solution twice
weekly for five weeks produced only slight tissue reactions (Grasso &
Three cats were given daily per os doses of 0.25, 0.50 and
0.75 g of a 5% aqueous solution of the colour. No abnormalities were
found (Truhaut, 1962).
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 80 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 1% 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. A long-term study in a second species is
required as well as a short-term study in a non-rodent species. These
have not been supplied.
The previous temporary ADI has been withdrawn.
Gangolli, S. D., Grasso, P. & Goldberg, 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