ERYTHROSINE
Explanation
Erythrosine (FD&C Red No. 3) is widely used as a coloring agent
for foods, beverages, pharmaceutical preparations, and cosmetics. It
has been evaluated for acceptable daily intake by the Joint FAO/WHO
Expert Committee on Food Additives (see Annex 1, Ref. Nos. 8, 19 & 35)
in 1964, 1969 and 1974. At the 18th Meeting (1974) of the Committee,
an ADI of 0 - 2.5 mg/kg body weight was allocated. Toxicological
monographs, were published in 1970 and 1975 (Annex 1, Ref. 20 and 36).
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
The metabolic behaviour and excretory pattern for erythrosine
have been studied in adult rats. The colour was given by stomach tube
in log-spaced doses from 0.5-500 mg per kg body weight. In five days
the recovery in the excreta was 102%. After an intravenous application
of 3 mg per kg body weight the urine and bile for the initial two to
four hours was collected, an average of 55% (50.4 - 58.0%) of the
administered quantity was found in bile. In the urine, the recovery
was 1.3% (0.3 - 1.8%). No glucuronic acid conjugation was found. The
colour was found to be largely excreted in the faeces by rats
(55 -72%) and despite the presence of two groups capable of undergoing
conjugations, no colour could be identified in the urine. A small
amount of the colour (0.4 - 1.7%) was excreted in the bile (Daniel,
1962).
Consideration has been given to the possibility that iodide may
be liberated from erythrosine and may disturb thyroid function. In
the rat, erythrosine is metabolically stable and 100% of the amount
is ingested and excreted with its iodine content intact after
administration of 500 mg/kg (Webb et al., 1962). Protein-bound and
total blood iodine levels were elevated in rats given erythrosine by
stomach tube twice weekly in a chronic study (Bowie et al., 1966).
However, the elevated PBIs (protein-bound iodine) were due to
interference by erythrosine in PBI determinations rather than thyroid
dysfunction in rats and gerbils (Anonymous, 1969).
In man, oral administration of 16 mg of erythrosine daily for 10
days resulted in an increase of protein-bound iodine in the serum from
6-11 µg/100 ml after 15 to 20 days, followed by a sharp decline in
iodine levels in the next 10 days with gradual return to the initial
value in three months (Anderson et al., 1964). Erythrosine could be an
adventitious source of iodide (Vought et al., 1972). No biologically
significant increases in plasma inorganic iodine or in urinary iodine
excretion were found in six patients (ages 25-68 years, sex not
reported) after oral exposure to 1.9 µmol (1,680 µg)/day of
erythrosine for ten days. In other assays of thyroid function, thyroid
radioiodine uptake, levels of thyroxine and protein bound iodine (PBI)
in plasma remained unchanged (Berstein et al., 1975).
Large doses of erythrosine labelled with I131 given orally to
rats inhibited uptake of 1131 by the thyroid of treated animals. Daily
doses over 1 mg are necessary for this effect (Marignan et al., 1965).
When cherries coloured with erythrosine are stored in plain cans,
fluorescein is readily formed by interaction of the tin-iron couple
present. This does not occur in lacquered cans. The production of
fluorescein (with 4 I atoms) from erythrosine occurs in presence of
metallic iron and/or tin and free organic acid (result of
electrochemical reduction in the can) (Dickinson & Raven, 1962).
It was found that this colour in a concentration of 200-400 mg/l,
inhibited the action of pepsin but had no effect on lipase activity
(Diemair & Hausser, 1951).
It was also found that this colour had in vivo as well as
in vitro haemolytic effect. In the in vivo studies the mouse was
used (Waliszewski, 1952).
Erythrosine was administered to rats in doses of 5, 10, 15 and
50 g per rat weighing 200-250 g twice weekly for six months.
Haemoglobin was reduced at three months as was the red cell count. The
cholesterol levels of males were depressed. Excretion of the dye was
mainly in the faeces and predominantly unchanged (Bowie et al., 1966).
TOXICOLOGICAL STUDIES
Special studies on carcinogenicity
(see under long-term studies)
Special studies on mutagenicity
This colour was tested for mutagenic activity and showed a very
slight but statistically significant mutagenic effect on Escherichia
coli in concentrations of 0.5 g/100 ml. It was found that the
xanthene molecule itself was the causative factor and that the
substituent groups only modify the effect (Lück et al., 1963; Lück &
Rickeryl, 1960).
The lack of mutagenic activity of erythrosine for Salmonella
typhimurium strains (TA 1535, TA 100, TA 1538, TA 98 and TA 1537)
was observed when tested in the Ames test at concentrations ranging
from 1 to 10,000 µg/plate with or without metabolic activation system
(Auletta et al., 1977; Bonin & Baker, 1980; Brown et al., 1978).
Erythrosine was inactive in the host-mediated rec - Assay (Kada et
al., 1972), in DNA-repair, fluctuation and treat-and-plate assays
(Haveland-Smith et al., 1981) and did not induce rat embryo calls
transformation in vitro (Price et al., 1978).
Special studies on reproduction
Rat
Four groups of Charles River CD rats (23-25 males and
females/group) received erythrosine in the diet at dose levels of 0,
0.25, 1.0 or 4.0% for 3 consecutive generations. The Fo parental rats
received their respective diets for 69 days prior to mating. The study
showed that during the gestation period slight to moderate reduction
in mean material body weight gain was noted in females of all
generations at the 1.0% and 4.0% dose levels. Slight to moderate
reductions in mean pup body weight was recorded at the 4.0% level on
lactation days 0, 4, 14 and 21 in all generation. These reductions
were statistically significant only on lactation day 21. These were no
consistent compound related effects on the reproductive performance of
males and females and pups survival at any dose level in any
generation (Albridge et al., 1981).
Groups of 18-22 pairs (males and females, weighing 200-220 g) of
adult Sprague-Dawley rats were fed diets containing erythrosine at
levels of 0, 0.25, 0.5 or 1.0% for 2 weeks before mating and during
mating period. The diets were continued for the females throughout
gestation and lactation and were provided continuously to their
offspring until they reached 90-100 days. Positive control group did
not receive erythrosine in the diet but offspring were injected daily
with 50 mg/kg of hydroxyurea on post-natal days 2-10 of life. Two
years later, a second experiment, a replication of the first one with
the same dose groups and number of animals per group was performed. In
both experiments, parental animals were evaluated for weight and food
consumption and females for reproductive success. The offspring were
assessed for behaviour toxicity plus weight, food consumption,
physical development, and brain weight. Erythrosine produced no
reductions in paternal or offspring weight or food consumption.
Erythrosine significantly increased preweaning offspring mortality at
the 1.0 and 0.5% dose levels in the first experiment, but not in the
second. Mean litter size was not adversely affected by erythrosine in
both experiments. Behaviourally, erythrosine produced no
dose-dependent effects that replicated across the two experiments. It
was concluded that no evidence was obtained that erythrosine via
dietary exposure at levels as high as 1.0% is psychotoxic to
developing rats (Vorhees et al., 1983).
Acute toxicity
Animal Route LD50 Reference
mg/kg bw
Mouse Oral 6800 Butterworth et al., 1976a
i.p. 360 Butterworth et al., 1976a
i.v. 370 Waliszewski, 1952, DFG, 1957
Rat i.p. 300 Emerson & Anderson, 1934
350 Butterworth et al., 1976a
Oral 1895 Lu & Lavallee, 1964
7100 Butterworth et al., 1976a
1840 Hansen et al., 1973a
Rabbit i.v. 200 Emerson & Anderson, 1934
Gerbil Oral 1930 Anonymous, 1969
A group of five young rats was given subcutaneous injections
twice daily for three days. The rats were killed on the fourth day.
The colour was administered in aqueous solution at a level of
250 mg/kg body weight each injection. No oestrogenic activity
(normal uterine weight) was detected (Graham & Allmark, 1959).
In experiments with guinea-pigs, it was found that this colour had no
sensitization activity (Bär & Griepentrog, 1960).
Short-term studies
Rat
In a 90-day study on five groups of 15 male and 15 female rats,
erythrosine was given in the diets at 0.25%, 0.5%, 1% and 2%. No
adverse effects were noted as regards body weight, food intake,
haematology, blood and urine analyses which were related to
administration of test substance. Organ weights were normal except
that absolute and relative caecal enlargement was seen at all levels
tested. It was dose-related but histology was normal. Absolute and
relative thyroid weight was increased at the 2% level. Histopathology
showed no abnormalities except pigment deposition in renal tubules in
females only at the 2% level but in males at all levels again in a
dose-related manner. The pigment was identified as protein-bound
erythrosine. In addition, total PBI was raised at all levels in a
dose-related manner, protein-bound erythrosine in serum behaved
similarly and non-protein bound iodine also increased with dose
levels. Thyroxine iodine however remained unchanged and I131 uptake
was reduced (Hansen et al., 1973b).
Five groups of Carwoth Farm E strain SPF rats (15 males and 15
females/group) received 0, 0.25, 0.5, 1.0 or 2.0% erythrosine in the
diet for 90 days. There were no effects attributable to treatment on
the rate of body weight gain, food intake, results of hematological
examination, serum analyses or renal function tests. Thyroid weight
relative to body weight was slightly increased in rats receiving 1.0%
and 2.0% erythrosine. Thyroid activity was not impaired by any dietary
level of erythrosine. This was indicated by the normal histopathology
of the organ, the lack of effect on serum thyroxine levels, and the
normal rates of oxygen consumption in the treated animals (Butterworth
et al., 1976a).
Groups of Sprague-Dawley female rats (12-20 animals per group)
were exposed to erythrosine in the diet at dose levels of 0 or 2.0%
for either 6 or 12 months. During the last 12 weeks of the
experimental period, a slight decrease of body weight gain was
observed in rats exposed for 12 months. Other parameters such as food
consumption, hematology, clinical chemistry, urinalysis and organ
weights were comparable among treated and control rats in both the six
and twelve month groups. Sporadic pathological changes were observed
in treated and control rats (Sekigawa et al., 1978).
Gerbil
Three groups of gerbils (15 males and 15 females/group) received
erythrosine in the diet at dose levels of 200, 750 or 900 mg/kg for 19
months (those animals in the 900 mg dosage group received 1200 mg/kg
for the first 3 months). The control group consisted of 30 males and
30 females. Body weight decreases were seen in male gerbils at all
feeding levels. However, this weight loss was observed in females only
ath the 900 mg/kg level. Elevated PBIs, due to interference by
erythrosine with PBI determination, were seen. No other haematological
differences were seen. No adverse gross pathology was noted.
Histopathology was not performed (Anonymous, 1969).
Dog
Two-year feeding studies were conducted with groups of three male
and three female beagles at levels of 0, 0.5, 1.0 and 2.0% in the
diet. All dogs survived the study. No gross or microscopic pathology
related to colour administration was seen (Hansen et al., 1973b).
Pig
Four groups of the Large White strain pigs (3 males and 3
females/group) weighing approximately 20 kg) were fed erythrosine in
their diet at dose levels of 0, 167, 500 or 1500 mg/kg/day for 14
weeks. The treated pigs exhibited decreased levels of serum thyroxine
when compared with controls. There were dose-related increases in the
serum levels of protein-bound iodine, iodine not bound to protein and
protein-bound erythrosine in animals of all treated groups. A dose
related increase in thyroid weight was noted, although the differences
were statistically significant only in female pigs at the higher dose
levels (500 and 1500 mg/kg/day) when compared with the controls. None
of the treated pigs revealed pathological changes of the thyroid
(Butterworth et al., 1976b).
Long-term studies
Mouse
A total of 122 male and female mice produced by mixed breeding
from five different strains were given a diet containing 1 mg per
animal per day of the colour. Mice at the age of 50-100 days were
used. A number of the animals were sacrificed after an observation
period of 500 days and the remaining mice after 700 days. A total of
168 mice was used as the control group. Positive control groups which
were given 0-aminoazotoluene and dimethylaminoazobenzene were also
included. In these groups the formation of liver tumours was noted
after approximately 200 days. The incidence of tumours in mice
receiving the colour was not significantly greater than in the
controls (Waterman & Lignac, 1958).
Chronic feeding studies were conducted with mice. Seventy mice
were fed at 1 and 2%. Because of the small number of animals surviving
the experiment and the small number of tumours found, no effect of
tumour formation could be attributed to the colour (Anonymous, 1969).
Five groups of Charles River CD-1 mice (60 males and 60
females/group) were exposed to erythrosine in the diet at dose levels
of 0 (two control groups were used), 0.3, 1.0 or 3.0% for 24 months.
(Average consumption of erythrosine, for males - 0, 424, 1474 or
4759 mg/kg/day and for females - 0, 507, 1834 or 5779 mg/kg/day). With
the exception of significant decreased body weights (throughout the
entire study) of males and females at the 3.0% dose level, other
investigated parameters (mortality, food intake, hematology, gross and
histopathology) were not adversely affected by erythrosine treatment
at any dose level (Richter et al., 1981).
Two groups of 7-week old ICR mice, weighing 27-38 g (50 males and
50 females/group) were fed a diet containing erythrosine at dose
levels of 1.25% or 2.5% for 18 months. All animals of experimental
groups were fed the basic diet free of erythrosine for the additional
6 months then sacrificed and autopsied. The control group consisted of
45 males and 45 females. Treated mice received erythrosine in a cube
diet for the first 20 weeks, and thereafter, the erythrosine was mixed
with the basic powder diet. The mortality was greater among animals
exposed to erythrosine than among the controls (approximately 61%
animals died in the 2.5% group, 59% in the 1.25% group and 36% in the
control group). Body weight gains were not adversely affected by
erythrosine ingestion. Animals of all experimental groups exhibited
high incidence of lymphcytic leukemia and sporadic cases of pulmonary
adenomas were also observed. The frequency of both lesions was in the
range spontaneously occurring in this strain of mice. The results
indicated that erythrosine was not carcinogenic to ICR mice under the
experimental conditions utilized (Yoshii & Isaka, 1984).
Rat
Groups of 24 weanling rats, evenly divided by sex, were fed this
colour at 0, 0.5, 1.0, 2.0 and 5.0% for two years. Slight growth
depression was observed in the animals at the 5% level, and those
above 0.5% had distended caeca but microscopically the distended caeca
showed normal histology. The statistical evaluation of the rat study
revealed no significant changes in organ weights at the highest level.
There was some diarrhoea at the 5% level. There was no difference in
survival (Anonymous, 1969).
The colour was fed at a level of 4% of the diet to five male and
five female rats for periods up to 18 months. Gross staining was
observed in the glandular stomach and small intestine and granular
deposits in the stomach, small intestine and colon. Hepatic cirrhosis
was noted in one out of four rats living up to 12 months. Fifty
control animals observed for 20 months or more failed to develop
tumours, or hepatic cirrhosis (Willheim & Ivy, 1953).
Groups of 12 male and 12 female weanling Osborne-Mendel rats were
fed 0, 0.5, 1.0, 2.0 and 5.0% erythrosine in their diet for two years.
Growth depression was observed in rats given 5%. The relative spleen
weight was depressed in all male test groups and in females at the 5%
level. Slight caecal enlargement was noted at 1% and increased with
dose but the histology of the enlarged caeca was normal. No other
gross or histopathological findings related to colour administration
were noted (Hansen et al., 1973b).
Groups of 25 male and 25 female 100-day-old rats and a group of
50 male and 50 female controls were fed 0, 0.5, 1.0, 2.0 and 4.0%
erythrosine in their diet £or 86 weeks. Other groups of 25 male and 25
female rats aged 100 days were intubated twice a week for 85 weeks
with erythrosine at 0, 100, 235, 750 and 1500 mg/kg body weight. After
this treatment animals were kept on normal diets for two years. Body
weight decreases were seen at 2 and 4%. Elevated PBI, due to
interference by erythrosine with PBI determination rather than thyroid
dysfunction, were seen. Thyroxine-iodine levels were not affected.
There were no other haematological differences and no anaemia was
seen. No adverse gross pathology was noted; histopathology had not
shown any colour related abnormalities (Hansen et al., 1973b).
Groups of 70 males and 70 females Charles River CD weanling rats
were fed erythrosine in the diet at levels of 0.1, 0.5 or 1.0% for 30
months after in utero exposure. Two concurrent control groups
(70 animals/sex/group) received no colour in the diet. The
average consumption of erythrosine was, for males - 0, 49, 251 or
507 mg/kg/day and for females 0, 61, 307 or 642 mg/kg/day. There were
no consistent significant compound related effects during the in
utero phase. In the main study, there were no consistent
significant compound-related effects on the following; physical
observation, behaviour, mortality, food consumption, hematology,
clinical chemistry, urinanalysis and ophthalmological findings. Mean
body weights of control and treated rats did not differ significantly
during the exposure period. The gross pathological changes noted could
not be attributed to treatment with erythrosine. The incidence of non
neoplastic lesions was comparable between treated and control groups.
There was a statistically significant increase in the incidence of
benign thyroid tumours (follicular adenoma): 6/68 in the 1.0% female
test group vs. 0/140 in the control group. The incidence of malignant
tumors in rats of treated groups was comparable with that of the
controls (Brewer et al., 1981).
Two groups of Charles River CD weanling rats (70 males and 70
females/group) were given erythrosine in the diet at dose levels of 0
or 4.0% for a period of approximately 29 months after in utero
exposure. The average consumption of the erythrosine was: male 0 or
2465 mg/kg/day, female 0 or 3029 mg/kg/day. There were no consistent
significant compound-related effects on the following; physical
observations, behaviour, mortality, food consumption, hematology,
clinical chemistry, urinanalysis and ophthalmological findings. Mean
body weights of treated rats (both sexes) were slightly lower
throughout the study than the control rats. These differences were
statistically significant except weeks 3-5 and 122 (male) and weeks
0-4, 6 and 114 (female). The mean absolute and relative thyroid
weights for treated males (4.0%) were more than doubled when compared
with the controls. The histopathological examination revealed that the
incidence of thyroid hyperplasia (follicular and C-cell) was
significantly increased in treated males. There was a statistically
significant increase in the incidence of follicular adenoma of the
thyroid in treated male rats (16/68 in treated group vs. 0/69 in the
control group) when compared with the controls. The incidence of
malignant tumors, including thyroid C-cell and follicular carcinoma,
was comparable among treated and control rats (Brewer et al., 1982).
Groups of 6-week old pathogen-free Fischer (F344) rats (50 males
and 50 females) were fed diets containing erythrosine at levels of
1.25 or 2.5% for 18 months. The control group consisted of 30 males
and 30 females and received a diet free of erythrosine. For the first
20 weeks of treatment, erythrosine was given in pelleted diet and for
the remaining treatment period in powder diets. Rats exposed to
erythrosine were sacrificed at 18 months and the control rats at 24
months after the start of the study. No parameters other than
histopathology were reported. Histopathology revealed sporadic cases
of spontaneous neoplasms (tumors of genital system, endocrine system,
hematopoietic system and digestive system) but their frequencies were
similar among animals of erythrosine treated groups and comparable to
the controls. No pathological changes were observed in the thyroid
glands (Fukunishi et al., 1984).
A study was undertaken to investigate whether the thyroid tumors
found after chronic feeding of erythrosine to male rats at a dose
level of 4.0% in the diet resulted from excess iodine (either as a
contaminant of the colour or as iodine metabolized from the colour) or
from another non-iodine-related property of the erythrosine. The study
was composed of six dose groups each containing 70 (35 males and 35
females) Charles River CD rats.
Group 1 - received unadulterated diet.
Group 2 - received 80 µg of Na1 (sodium iodide)/g of diet.
Group 3 - received purified erythrosine at 4.0% level in the diet.
Group 4 - received purified erythrosine at 4.0% level in
the diet plus 80 µg of Na1/g of diet.
Group 5 - received purified erythrosine at 4.0% level in
the diet plus 160 µg of Na1/g of diet.
Group 6 - received commercial erythrosine at 4.0% level in the diet.
Exposure continued for 27 weeks. The study demonstrated that
feeding of commercial erythrosine at a level of 4% in the diet
produces an endocrine state of hyperthyroidism. Thyroid stimulating
hormone (TSH) and thyroxine (T4) levels were elevated and
tri-iodothyronine (T3) concentrations were depressed. Changes in
clinical chemistry parameters, body weight, and food consumption were
also indicative of hyperthyroidism. Additional purification of the
commercial preparation of erythrosine to remove free iodide did not
modify the responses described. These responses were not found after
feeding a diet spiked with Na1 only (80 µg/g of diet). This study
demonstrated that thyroid changes observed in this and former studies
are associated with increased TSH concentration. However, the results
of this study do not indicate the mechanism for these effects of
erythrosine (Couch et al., 1983).
Twenty rats were subject to weekly subcutaneous injections of
1 ml of a 5% aqueous solution for 596 days (85 weeks). The total
quantity of colour administered was 2.65 g/animal. Seven rats survived
300 days or more. No tumours were observed (Umeda, 1956).
Eighteen rats were injected subcutaneously with aqueous solutions
of erythrosine at 12 mg/animal once per week for two years. No tumours
either at the injection sites or in other parts of the body were
observed (Hansen et al., 1973b).
Gerbil
Three groups (15-16 animals/sex/group) of Mongolian gerbils,
approximately 6 months old, were fed diets containing erythrosine at
levels of 1.0, 2.0 or 4.0% for 105 weeks. Control groups (31 animals
of each sex) were fed diets free of erythrosine. Animals of all
treated groups exhibited a statistically significant dose-related
decrease in body weight gain when compared with the controls. In
general, there were slight, and in some isolated cases, significant
depressions of hematocrit and hemoglobin values, and leucocyte and
reticulo-cyte counts in animals of treated groups. The relative
weights of heart, liver and spleen were significantly decreased in
animals of both sexes at the two high dose levels (2.0 and 4.0%).
Dose-related changes such as enlargement of follicles and, in some
cases, focal hyperplasia were observed in the thyroid of treated
animals. Histopathology did not reveal any treatment related effects
(Collins & Long, 1976).
Groups of 20-24 males and 20-24 females Mongolian gerbils
approximately 6 months old received erythrosine (dissolved in water)
by stomach intubation at dose levels of 200, 750 or 900 mg/kg twice
weekly for 97 weeks. A control group (32 animals/sex) was intubated
with distilled water only. The dosages were administered in a volume
of 10 ml/kg body weight. No treatment-related adverse effects were
observed for investigated parameters such as clinical toxicity,
mortality, body weight gain, hematology, organ weights, gross and
histopathology (Collins & Long, 1976).
OBSERVATIONS IN MAN
Five human volunteers (four males and one female, ages 21-35
years) received erythrosine in a diet at dose levels of 5, 10 or
25 mg/day in weekly increments for a period of 3 weeks. The study
demonstrated slowly and slightly increasing levels of total serum
iodine and protein bound iodine (PBI) associated with the weekly
increasing erythrosine doses. In the other tests for serum T4, T3,
TSH, erythrosine concentration, urinary iodine and erythrosine
excretion, and T3 - resin uptake remained unchanged throughout the 3
weeks. Increases in serum PBI and total serum iodine during exposure
period indicates that a portion of the iodine ingested as erythrosine
appears to be absorbed from the gastrointestinal tract. No changes in
concentration of TSH, T4 and T3 in serum indicate that both the
thyroid function and thyroregulatory mechanisms were unaffected by the
ingestion of erythrosine during a three week period at a dose as high
as 25 mg/day (Ingbar et al., 1983).
Comments
The Committee considered information obtained since 1974 which
included: measurements of thyroid function in human subjects ingesting
erythrosine; data on mutagenicity; data on reproduction and
behavioural toxicity; the results of long-term feeding studies in mice
and rats; and the results of 90-day and 6-month studies in rats, in
which effects on the thyroid function were demonstrated. In the latter
studies it was shown that the effects on the thyroid function were not
due to sodium iodide, which is normally present in the commercial
product. The results of tests for mutagenicity were negative. The
Committee considered that the development of thyroid tumours in the
long-term studies on rats might be mediated by a hormonla effect,
although the mechanism for this was not demonstrated. One way of
determining the no-effect level would have been by assessing the
extent of diffuse hyperplasia in the thyroid glands of erythrosine-
treated rats, as this was likely to have accompanied the observed
increase in thyroid weight and would indicate an effect on thyroid
function. However, the data for this purpose were not available to the
Committee. Because insufficient data were available to determine a
no-effect level, the existing ADI was reduced to 0-1.25 mg/kg of body
weight and made temporary.
EVALUATION
Level causing no toxicological effect
Rat: 0.5% (=5000 ppm) in the diet equivalent to 250 mg/kg body
weight.
Estimate of temporary acceptable daily intake for man
0-1.25 mg/kg body weight.
FURTHER WORK OR INFORMATION
Required by 1986
1. The histopathology (including the assessment of diffuse
hyperplasia) of all thyroid glands from the recent long-term
studies in rats.
2. The mechanism of the effects of erythrosine on the thyroid gland,
in terms of the biochemical and histopathological parameters; and
the existence of a threshold level of these effects and their
reversibility.
Desirable
Information on the pharmacokinetics of erythrosine and its effect
on the thyroid functions of human subjects.
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See Also:
Toxicological Abbreviations
Erythrosine (FAO Nutrition Meetings Report Series 46a)
Erythrosine (WHO Food Additives Series 6)
Erythrosine (WHO Food Additives Series 21)
Erythrosine (WHO Food Additives Series 24)
Erythrosine (WHO Food Additives Series 28)
Erythrosine (WHO Food Additives Series 44)
ERYTHROSINE (JECFA Evaluation)