INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
WORLD HEALTH ORGANIZATION
SUMMARY OF TOXICOLOGICAL DATA OF CERTAIN FOOD ADDITIVES
WHO FOOD ADDITIVES SERIES NO. 12
The data contained in this document were examined by the
Joint FAO/WHO Expert Committee on Food Additives*
Geneva, 18-27 April 1977
Food and Agriculture Organization of the United Nations
World Health Organization
* Twenty-first Report of the Joint FAO/WHO Expert Committee on Food
Additives, Geneva, 1977, WHO Technical Report Series No. 617
ORANGE GGN
EVALUATION FOR ACCEPTABLE DAILY INTAKE
BIOLOGICAL DATA
BIOCHEMICAL ASPECTS
Excretion
The colour was injected intravenously into rats. The bile was
collected for six hours and analysed. The recovery of the colour was
an average of 23% (10-40%) of the administered quantity (Ryan and
Wright, 1961).
Effect on enzymes
After a prolonged administration to two generations of rats with
a daily dose of 50 mg/rat the vitamin A content of the liver showed a
three-to four-fold decrease. The glutathione content of the spleen was
increased in the first generation, not in the second (Galea et al.,
1963).
At 6.66 mg dye/ml succinic acid dehydrase was inhibited and
xanthine oxidase was weakly inhibited (Schormüller and Schulz, 1958).
The products of air-oxidation or reduction and subsequent
air-oxidation of Orange GGN inhibited lactic acid fermentation of milk
(Eisenbrand and Lang, 1960; Lang, 1967).
TOXICOLOGICAL STUDIES
Special studies on carcinogenicity
A group of 10 male rats was fed 1-(m-sulfophenylazo)-2-naphthol-
6-sulfonic acid, disodium salt at 0.02-0.1% in food (10 mg/kg body
weight per day) to assess carcinogenicity. After at least 410 days,
there were nine survivors but no tumours were observed. There was no
increase in Heinz bodies (Hecht and Wingler, 1952).
Five male and five female rats were given in their drinking water
0% or 1.0% of the colour for 266 days. The average daily intake was
0.75 g/kg body weight. Total intake was 50 g/animal. Observation
period was 545 days. No tumours were found (Deutsche Forsch., 1957).
Five male and five female rats were given this colour at a level
of 0% or 1% in the drinking water for 262 days. The average daily
intake was 0.9 g/kg body weight. The total intake of the colour was
52 g/animal. The animals were kept under observation for 832 days. Two
of the animals died before the end of the experiment. No tumours were
observed (Deutsche Forsch., 1957).
Ten rats were fed at a level of 0.1% in the diet for a period of
410 days. The average daily dose was 0.06 g/kg. The total intake
6 g/animal. The animals were kept under observation for 761 days. One
animal died before the end of the experiment. No tumours were observed
(Deutsche Forsch., 1957; Hecht and Wingler, 1952).
Two groups of 10 rats were subjected to subcutaneous injections
of 0.5 ml of a 1% solution of the colour twice weekly for respectively
364 and 365 days. Total intake in both groups of rats was
0.5 g/animal. The animals were kept under observation for 521 and
839 days. Two animals died before the end of the experiment. In one
animal a poly-morphocellular tumour in the lung and in another rat a
fibromyoma at the site of injection was observed (Deutsche Forsch.,
1957).
Other special studies
This colour was tested for mutagenic effect in a concentration of
0.5 g/100 ml in cultures of Escherichia coli. No mutagenic effect
was found (Lück and Rickerl, 1960). Five rats were given 1.4 g of
colour per kg body weight for 22 days. No Heinz bodies were found in
the blood of the animals (Deutsche Forsch., 1957). In experiments with
guinea-pigs it was found that this colour has no sensitization
activity (Bär and Griepentrog, 1960). A negative test for Heinz bodies
was obtained on a cat given 0.1 g/kg orally for seven days (Deutsche
Forsch., 1957; Hecht and Wingler, 1952). In another test in cats given
200 mg/kg orally for six days no Heinz bodies were found (Wingler,
1953).
Acute toxicity
Animal Route LD50 per kg References
body weight
Mouse oral >5.0 g Deutsche Forsch, 1957
Rat i.p. >2.0 g Deutsche Forsch, 1957
>1.0 g A.B. Shporn et al., 1958
Rat i.v. Approx. 2.5 g Deutsche Forsch, 1957
Long-term studies
Mouse, rat
Mice and rats were treated with Orange GGN to assess chronic
toxicity. No effects on haematology, clycaemia, or protein synthesis
were observed (Sporn and Heilpern, 1958).
Rat
Rats were treated with Orange GGN to assess chronic toxicity at
about 125 mg/kg daily. After prolonged administration, vitamin A
content of liver decreased three- to four-fold with parallel decrease
in glutathione in liver and spleen (Galea et al., 1962).
See also special studies on carcinogenicity.
REFERENCES
Bär F. and Griepentrog, F. (1960) Die Allergenwirkung von Fremden
Stoffen in den Lebensmitteln, Med. u. Ernähr., 1, 99-104
Deutsche Forschungsgemeinschaft (1957) Bad Godesberg, Federal Republic
of Germany, Farbstoff Kommission, Mitteilung, 6, 32
Eisenbrand, J. and Lang, E. (1960) Influence of azo dyes on acid
production of lactic acid bacteria. V. Action of cleavage and air-
oxidation products of Brilliant Black BN, Chrysoin, S., Echtgelb
Extra, Yellow 27175 N, Yellow Orange S, Orange GGN and Tartrzine,
Z. Lebensm.-Untersuch. u.-Forsch., 113, 48-52
Galea, V., Ariesan, Maria and Luputiu, Georgeta (1962) Biochemical
alterations in the liver of white rats under the influence of
synthetic organic dyes, Orange GGN and Amaranth, Farmacia
(Bucharest), 10, 531-533
Hecht, G. and Wingler, A. (1952) Biological study and suitable
chemical constitution of some azo dyes for food colouring,
Arzneimittel-Forsch., 2, 192-196
Lang, E. (1967) Cleavage products of the azo dyes, Brilliant Black BN,
Yellow Orange S, Orange GGN and their effect on acid production by
lactic acid bacteria, Z. Lebensm.-Unters. Forsch., 132, 363-367
Lück, H. and Rickerl, E. (1960) Lebensmittelzusatzstoffe und mutagene
Wirkung, Z. Lebensmitt.-Untersuch. u.-Forsch., 112, 157-174
Ryan, A. J. and Wright, S. E. (1961) The excretion of some azo dyes in
rat bile, J. Pharm. Pharmac., 13, 492-495
Schormüller, J. and Schulz, W. B. (1958) Action of food colour on the
succinic acid dehydrase and xanthine oxidase in vitro, Z. Lebensm.
-Untersuch. u.-Forsch., 108, 9-17
Shporn, A. B., Peretsiana, Zh. M. and Gal'perin, S. (1958) Studies on
the toxicity of chemicals added to food, Voprosy Pitaniya, 17, No.
4, 48-53
Sporn, A. and Heilpern, J. (1958) The toxicity of the Orange GGN food
colouring, Igiena, 7, 235-243
Wingler, A. (1953) Über Farbstoffe zur Lebensmittelfärbung. Zur Frage
der Krebsgefährdung, Z. Krebsforschung., 59, 134-155