INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
WORLD HEALTH ORGANIZATION
SUMMARY OF TOXICOLOGICAL DATA OF CERTAIN FOOD ADDITIVES
WHO FOOD ADDITIVES SERIES NO. 13
The data contained in this document were examined by the
Joint FAO/WHO Expert Committee on Food Additives*
Rome, 3-12 April 1978
Food and Agriculture Organization of the United Nations
World Health Organization
* Twenty-second Report of the Joint FAO/WHO Expert Committee on Food
Additives, Geneva, 1978, WHO Technical Report Series No. 631
This colour was evaluated at the Joint FAO/WHO Expert Committee
on Food additives in 1964, 1972 and 1975. Since the previous
evaluation, additional data have become available and are summarized
Special studies on teratology
A collaborative government-industry study was initiated to
evaluate the teratogenic potential of amaranth which involved three
laboratories: Food and Drug Administration (FDA), Industrial Bio-Test
Laboratories (IBT) and the National Center for Toxicological Research
Groups of 20 to 30 pregnant females received 200 mg/kg bw
amaranth by gavage during days 0-19, 6-15 or 7-9 of gestation. Another
group received amaranth at the same dose level in their drinking-water
from day 0 to day 20. Appropriate controls were utilized. The
Osborne-Mendel strain of rat was used by FDA while IBT used Charles
River and NCTR both strains. The Charles River strain in the IBT and
NCTR studies showed a significant increase in litters with two or more
resorptions after dams had been given 200 mg/kg by gavage from
day 0-19. As well, a significant increase in the percentage
resorption/litter was observed in this strain in the NCTR study. A
significant increase in resorptions was not observed in the
Osborne-Mendel strain. There were no apparent compound-related skeletal
or visceral effects (Collins et al., 1976a, 1976b; Keplinger et al.,
1976; Holsen et al., 1976a, 1976b).
Amaranth was administered daily by gelatin capsule to adult
female cats at dose levels of 0, 92, 187 or 264 mg/kg bw extending
from 22 days before gestation to day 61 or 62 of gestation. Seven
trials commencing at time intervals of 10 to 38 days were conducted.
Six trials contained 20 cats each and one contained 11 cats. The cats
in each trial were assigned randomly to five groups, three groups were
treated with amaranth and the remaining two groups served as controls.
The pregnancies were timed by having controlled copulation of females
that were in oestrus which occurred spontaneously or was stimulated by
gonadotrophin. Caesarian section was performed on day 61 or 62 of
gestation. No significant effects which could be related to the
ingestion of this colour were observed with respect to total implants,
ratio of corpora lutea to total implants, dead foetuses, deciduomas,
live foetuses, 24-hour viability of live foetuses in an incubator,
mean live foetal weight, sex ratio and foetal abnormalities (Khera et
Special studies on mutagenicity
Groups of 12 male mice were injected intraperitoneally with a 5%
aqueous solution of amaranth at dose levels of 0, 250 or 500 mg/kg bw.
Each male was then mated with three untreated females each week for
six weeks. Females were killed one week after their removal from
breeding cages and were examined for signs of pregnancy. The mating
indices and mutation rates gave no indication of a dominant lethal
response (Arnold et al., 1976).
Groups of weanling rats were fed diets containing amaranth at
levels of 0, 1200, 3000, 10 000 or 20 000 ppm for 10 days. The test
and control groups contained nine and 12 rats/group respectively. All
rats received 30 µg of vitamin A daily. No significant changes were
observed in body weight, food consumption, liver weight and vitamin A
content of the liver (Truhaut and Ferrando, 1975).
Groups of 50 male and 50 female weanling rats were fed amaranth
at 0, 0.003, 0.03, 0.3 or 3% (0, 1.5, 15, 150 or 1500 mg/kg bw) in the
diet for approximately two-and-a-half years. The rats used in this
study were randomly selected from the F2a litters of parents treated
with amaranth. During the study certain animals were inadvertently
placed in the wrong cages so that a number of animals were shifted
among the control and treated animals. A variety of benign and
malignant tumours was observed with no apparent differences between
the treated and control groups. When the pathological data, however,
were subjected to biostatistical analysis, a significant increase
in the number of malignant tumours was observed in the female rats
maintained at the 1500 mg/kg bw dietary level. There was no
significant difference in the total number of tumours, both benign and
malignant, between high dose and control animals. No compound-related
effects were noted with respect to general condition, survival, body
weight gain, haematology, clinical chemistry or relative organ weights
(Gordon and Taylor, 1975).
Arnold, D. W., Kennedy, G. L., jr, Keplinger, M. L. and Calandra, J.
C. (1976) Failure of FD and C Red No. 2 to produce dominant lethal
effects in the mouse, Food Cosmet. Toxicol., 14, 163
Collins, T. F. X., Ruggles, D. I., Holson, J. F., jr, Schumacher, H.,
Gaylor, D. W. and Kennedy, G. L., jr (1976a) Teratological evaluation
of FD and C Red No. 2 - a collaborative government-industry study.
I. Introduction, Experimental Materials, and Procedures, J. Toxicol.
and Environ. Health, 1, 851
Collins, T. F. X., Black, T. N., Ruggles, D. I. and Gray, G. C.
(1976b) Teratological evaluation of FD and C Red No. 2. A
collaborative government-industry study. II. FDA's study,
J. Toxicol. and Environ. Health, 1, 857
Gordon, L. A. and Taylor, J. M. (1975) Chronic feeding study of
amaranth in rats, unpublished data from FDA-US
Holson, J. F., jr, Schumacher, H. J., Gaylor, D. W. and Gaines,
T. B. (1976a) Teratological evaluation of FD and C Red No. 2 - A
collaborative government-industry study. IV. NCTR's study,
J. Toxicol. and Environ. Health, 1, 867
Holson, J. F., jr, Gaylor, D. W., Schumacher, H. J., Collins, T. F.
X., Ruggles, D. I., Keplinger, M. L. and Kennedy, G. L., jr (1976b)
Teratological evaluation of FD and C Red No. 2 - A collaborative
government-industry study. V. Combined findings and discussion,
J. Toxicol. and Environ. Health, 1, 875
Keplinger, M. L., Kinoshita, F. K., Smith, S. H. and Kennedy, G. L.,
jr (1976) Teratological evaluation of FD and C Red No. 2 - A
government-industry study. III. IBT's study, J. Toxicol. and
Environ. Health, 1, 863
Khera, K. S., Roberts, G., Trivett, G., Terry, G. and Whalen, C.
(1976) A teratogenicity study with amaranth in cats, Toxicol. appl.
Pharmacol., 38, 389
Truhaut, R. and Ferrando, R. (1975) Influence de l'administration par
voie orale, de differentes doses de deux colorants azoiques,
l'Amarante et le Jaune Soleil FCF, sur la mise en réserve de la
vitamine A dans le foie du rat, C.R. Acad. Sci., Paris t. 281
(4, 11, 18, 25 août 1975)