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
YELLOW 2G
EVALUATION FOR ACCEPTABLE DAILY INTAKE
BIOLOGICAL DATA
BIOCHEMICAL ASPECTS
Injection of 1 mg/kg bw i.v. into adult rats as an aqueous
solution resulted in 96% excretion in the bile (Ryan and Wright,
1961). It has been suggested that the biliary excretion rate is
related to the relative protein-binding properties of the dye in liver
and blood (Priestly and O'Reilly, 1966). It is possible that Yellow 2G
is metabolized in a similar manner to tartrazine which has a structure
related to Yellow 2G (Gaunt et al., 1971; Walker, 1970; Westöö, 1965).
Incubation of Yellow 2G with a buffered bacterial suspension from rat
intestine for four hours at 37° under oxygen-free nitrogen resulted in
38% azo-reduction of the colour (Roxon et al., 1967).
TOXICOLOGICAL STUDIES
Acute toxicity
No information available.
Short-term studies
Rat
Yellow 2G was fed to four groups of 15 male and 15 female rats at
dietary levels of 0, 100, 1000 or 10 000 ppm for 13 weeks. The
colourant was decolourized in the caecum yielding a colourless product
which turned red on exposure to the air. No adverse effects were seen
in the rate of body weight gain, or in the results of haematological
examinations, serum chemistry, renal cell excretion and concentration
tests. No gross or micropathological effects were detected which could
be attributed to the colourant. There were isolated changes of the
weights of kidney, small intestine, adrenal glands and testes in rats
receiving 1000 or 10 000 ppm Yellow 2G but these were not considered
to be related to treatment. The caeca were enlarged in rats fed a diet
containing 10 000 ppm (Gaunt et al., 1971).
Pig
Four groups of three pigs of each sex were given Yellow 2G in
doses of 0 (control), 5, 50 or 500 mg/kg/day for 15 weeks. The faeces
of the pigs at the two higher dose levels developed a reddish colour
on exposure to the air, probably due to oxidation of a metabolite of
the colouring. There was an initial diarrhoea lasting one or two days
in half the pigs at the highest dose level. No adverse effects were
seen in the rate of body weight gain, haematology, examination of
urine, organ weights or histopathological examination (Gaunt et al.,
1975).
Long-term studies
Mouse
Groups of 48 male and 48 female mice (TF1 strain) were given
diets containing 0 (control), 30, 300 or 1500 ppm Yellow 2G (purity
min. 85%) for 80 weeks. Additional groups of 16 male mice were given
diets containing 0 or 1500 ppm of the colour. There was a non-
significant reduction in rate of body weight gain at the two higher
dietary levels in males and isolated lower values for haemoglobin
concentration and erythrocyte count at these same levels in both
sexes. These findings together with increased values for relative
brain, liver and small intestine weight in the females given 1500 ppm
Yellow 2G were not considered to be related to treatment. There were
deaths in all groups during the study but at no time were there
significant differences between the groups. There were no effects
attributable to treatment in the incidence of histological lesions.
The most frequent kind of tumour in the mouse were lymphomas, but
there was no significant statistical difference between the groups
(Evans et al., 1975).
Rat
Groups of 48 male and 48 female rats (Wistar strain) were given
diets containing 0 (control), 100, 1000 or 10 000 ppm of Yellow 2G
(purity min. 85%) for 2 years. There were no treatment-related effects
on mortality, food and water intake, serum analyses or haematology.
There were slight decreases of weight gain in animals on the highest
dietary level and a decreased renal concentrating ability at week 104
in rats given 1000 or 10 000 ppm together with an increased kidney
weight in males on the highest level. Glomerulonephrosis was seen in
the majority of the animals, but there was essentially no difference
between treated and control animals, except in the low dose F where
there were significantly more "slight to moderate" (but less "severe")
lesions than in the controls.
The changes in kidney function and morphology are most likely an
expression of spontaneous degeneration which is normal in old
laboratory rats. The differences are most probably fortuitous and not
due to treatment with Yellow 2G. Most of the histopathological lesions
found were with similar frequencies in control and test animals. The
other findings were not dose-related. Most of the tumours were found
in controls alone or with similar frequencies in control and treated
animals. The other tumours of different type were found scattered
through all the groups but not dose-related. It was concluded that
Yellow 2G did not exert a carcinogenic effect in this experiment
(Hooson et al., 1975).
REFERENCES
Evans, J. G., Gaunt, I. F., Kiss, I. S. and Butterworth, K. R. (1975)
Longterm toxicity of Yellow 2G in mice, BIBRA research report No.
13/1975
Gaunt, I. F. et al. (1971) Fd. Cosmet. Toxicol., 9, 343
Gaunt, I. F. et al. (1975) Fd. Cosmet. Toxicol., 13, 1-5
Hooson, J., Gaunt, I. F., Hardy, J., Gangolli, S. D. and Butterworth,
K. R. (1975) Longterm toxicity study of Yellow 2G in the rat, BIBRA
research report No. 18/1975
Priestly, B. G, and O'Reilly, W. J. (1966) J. Pharm. Pharmacol.,
18, 41
Roxon, J. J., Ryan, A. J. and Wright, S. E. (1967) Fd. Cosmet.
Toxicol., 5, 367
Ryan, A. J. and Wright, S. E. (1961) J. Pharm. Pharmacol., 13, 492
Westöö, G. (1965) Acta. Chem. Scand., 19, 1309
Walker, R. (1970) Fd. Cosmet. Toxicol., 8, 659
See Also:
Toxicological Abbreviations
Yellow 2G (WHO Food Additives Series 6)
YELLOW 2G (JECFA Evaluation)