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.
INDANTHRENE BLUE RS
Explanation
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 1966 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.
BIOLOGICAL DATA
BIOCHEMICAL ASPECTS
No information available.
TOXICOLOGICAL STUDIES
Acute toxicity
LD50
Animal Route mg/kg bw Reference
Rat Oral 2 000 Lu & Lavalleé, 1964
In experiments with guinea-pigs it was found that this colour has
no sensitizing activity (Bär & Griepentrog, 1960). Cats received daily
doses of 0.1 g/kg colour for seven days. No increase in Heinz bodies
was noted in the blood of test animals (Oettel et al., 1965).
Short-term studies
Rat
This colour was fed to 21 rats at 0.1% in the diet for 184 days.
No increased tumour incidence was observed. Eight rats which survived
for more than 400 days (432-683) showed no abnormality. Twelve rats
also received monthly subcutaneous injections of 2 ml of a 2.5%
aqueous suspension of the colour. Six rats survived for 417-570 days.
No tumours were seen at the site of injection (Umeda, 1956).
Long-term studies
Rat
Eighty-five rats received this colour at 0.1% in their diet. No
increased tumour incidence was observed over their life-span. Twenty
rats, given 1% of the colour in their diet for two years, showed no
increased tumour incidence. Eleven animals died before the end of the
experiment (DFG, 1957).
Groups of 20 male and 20 female rats or more were fed diets
containing 0 ppm (0%) and 1% of the colour for two years. A similar
test group was formed from the first filial generation and was fed the
1% level for a similar period. No deleterious effects appeared in the
test groups, and gross and microscopic examination of the animals
disclosed no changes attributable to the test diet. There was no
significant difference in tumour incidence between the groups (Oettel
et al., 1965).
Comments:
The available long-term study in rats is not adequate as only
some selected parameters have been examined. There is no information
on metabolism or on its effect on reproduction, embryotoxicity and
teratogenicity. Previously this colour had been allocated a temporary
ADI subject to the provision of further essential information by 1974.
This has not been forthcoming.
EVALUATION
The previous temporary ADI has been withdrawn.
REFERENCES
Bär, F. & Griepentrog, F. (1960) Med. u. Ernär., 1, 9
Deutsche Forschungsgemeinschaft, Farbstoff Kommission (1957)
Mitteilung 6
Lu, F. C. & Lavalleé, A. (1964) Canad. pharm. J., 97, 30
Oettel, H., Frohberg, H., Nothdurft, H. & Wilhelm, G. (1965) Arch. für
Toxikol., 21, 9
Umeda, M. (1956) Gann, 47, 57