WORLD HEALTH ORGANIZATION
Toxicological evaluation of some food colours, thickening
agents, and certain other substancse
WHO FOOD ADDITIVES SERIES NO. 8
The evaluations contained in this publication were prepared
by the Joint FAO/WHO Expert Committee on Food Additives which
met in Geneva, 14-23 April 19751
World Health Organization, Geneva 1975
1 Nineteenth Report of the Joint FAO/WHO Expert Committee on Food
Additives, Wld Hlth Org. techn. Rep. Ser., 1975, No. 576;
FAO Nutrition Meetings Report Series, 1975, No. 55.
The monographs contained in the present volume are
also issued by the Food and Agriculture Organization
of the United Nations, Rome, as
FAO Nutrition Meetings Report Series, No. 55A
ISBN 92 4 166008 2
(C) FAO and WHO 1975
QUINOLINE YELLOW
Explanation
This compound was evaluated for acceptable daily intake for man
by the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1,
Refs No. 10, No. 20 and No. 35) in 1966, 1969 and 1974.
Since the previous evaluation additional data have become
available and are summarized and discussed in the following monograph
addendum. It should be noted that there are two types of quinoline
yellow, namely one a combination of methylated and non-methylated
materials, the second a wholly unmethylated material (see
specifications for particulars). In this monograph studies related to
the methylated product are indicated by an asterisk.
BIOLOGICAL DATA
TOXICOLOGICAL STUDIES
Special studies on teratogenicity
Rat
Groups of 20-24 pregnant Long-Evans rats received by gavage from
day six to 15 of gestation 0, 15, 50 or 150 mg/kg/day. Three control
groups were used and a positive control group of 22 rats was given
30 mg trypan blue/kg/day subcutaneously from days seven to nine. Rats
were sacrificed at day 20. No signs of maternal or foetal toxicity or
anomalies were seen attributable to the colour. Trypan blue produced
the expected abnormalities (Anonymous, 1972a).
Rabbit
Groups of 15 pregnant rabbits received by gavage from days six
to 18 of gestation 0, 15, 50 and 150 mg/kg/day. Three control groups
were used and a positive control group of 15 rabbits was given
150 mg/ kg/day thalidomide. Animals were sacrificed on day 29. No
significant maternal or foetal abnormalities due to the colour were
noted. Thalidomide produced the expected abnormalities (Anonymous,
1972b).
Special studies on mutagenicity
*This colour was tested for mutagenic effect in a concentration
of 0.5 and 1.0 g/100 ml in cultures of Escherichia coli. No
mutagenic effect was found (Lück & Rickerl, 1960).
Other special studies
*In guinea-pigs it was found that this colour had no
sensitization activity (Bär & Griepentrog, 1960). Cats received daily
doses of 0.1 g/kg colour for seven days. No increase in Heinz bodies
in the blood of the test animals was noted (Oettel et al., 1965).
Short-term studies
Rat
*Groups of five male and five female rats were fed diets
containing 0, 0.25%, 0.5%, 1.0%, 2.0%, and 5.0% for 90 days. No effect
on body weight, food intake, blood cell counts and organ weights were
observed (Hansen et al., 1960).
*Ten male and 10 female rats were given a total of 55
subcutaneous injections of 1 ml of 2% aqueous solution over a period
of seven months, then observed until death. No local tumours developed
and total tumour incidence was less than in control groups given
similar injections of glucose or salt solution (Oettel et al., 1965).
Dogs
*Groups of three male and three female dogs were fed diets
containing 0.03 and 0.2% of the colour for two years. The control
group consisted of 10 animals of each sex. No colour-induced effects
were noted in terms of body weight, food consumption, gross and
microscopic pathology.
Long-term studies
Rat
*Groups of 20 male and 20 female rats or more were fed diets
containing 0 and 1% of the colour for two years. A similar test group
was formed from the first filial generation and was fed at 1% level
for a similar period of time. No effect of the diet was noted in the
test groups and gross and microscopic examination of the animals
disclosed no charges attributable to the test diet. There was no
significant difference in tumour incidence between the groups (Oettel
et al., 1965).
*Twenty rats, half males and half females, received twice weekly
subcutaneously 1 ml of a 2% aqueous solution into the same site. A
total of 55 injections were given for seven months and animals
observed for 32 months. Three groups of 20 rats acted as controls. No
significant effects on behaviour, growth, mortality, microscopic
appearance of principal organs was noted. No tumours appeared at the
site of injection of test animals but one sarcoma at the injection
site and two tumours of ovary and uterus appeared in controls (Oettel
et al., 1965).
Groups of 25 male and 25 female rats were fed diets containing
0.0, 0.2 and 0.1% of the colour for up to two years. No colour-induced
effects were seen in terms of body weight, food intake, survival,
haematology, urinalyses, organ weights, gross and microscopic
pathology.
Comments:
In the manufacture of these colours the impurities are
qualitatively the same. Therefore toxicological data obtained on the
colour containing the methylated derivative could be used as
collateral evidence to assure also the safety of the non-methylated
preparation. There is no biological information on either preparation
but an adequate long-term study in rats is available. Additional
studies on non-rodents have also been evaluated. Multi-generation
studies are in progress but embryotoxicity including teratology has
already been studied in two species.
EVALUATION
Level causing no toxicological effect in the rat
0.1% (= 1000 ppm) in the diet equivalent to 50 mg/kg body weight
Estimate of acceptable daily intake for man
0-0.5 mg/kg body weight*
FURTHER WORK OR INFORMATION
Required by 1978 (June).
(1) Metabolic studies in several species, preferably including man.
(2) Adequate long-term studies in other species.
(3) Results of multi-generation study in progress.
* Temporary.
REFERENCES
Anonymous (1972a) Unpublished report from Biodynamics, Inc. submitted
to the World Health Organization by the Inter-Industry Color
Committee, United States of America
Anonymous (1972b) Unpublished report from Biodynamics, Inc. submitted
to the World Health Organization by the Inter-Industry Color
Committee, United States of America
Anonymous (1967a) Unpublished report from Hazleton Labs, Inc.
submitted to the World Health Organization
Anonymous (1967b) Unpublished report from Hazledon Labs, Inc.
submitted to the World Health Organization
Bär, F. & Griepentrog, F. (1960) Die Allergenwirkung von Fremden
Stoffen in den Lebensmitteln, Med. U. Ernaehr., 1, 99
Hansen, W. H., Wilson, D. C. & Fitzhugh, O. C. (1960) Subacute oral
toxicity of ten D & C coal-tar colors, Fed. Proc., 19, 390
Lück, H. & Rickerl, E. (1960) Lebensmittelzusatzstoffe und mutagene
Wirkung (Food additives and mutagenic effect). VI. Report,
Z. Lebensmitt.-Untersuch., 112, 157
Oettel, H., Frohberg, H., Nothdurft, H. & Wilhelm, G. (1965) Die
prüfung einiger synthetischer Farbstoffe auf ihre Eignung zur
Lebensmittelfärbung, Arch. Toxicol., 21, 9-29