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.



         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,

         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).


    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


         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


         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).


         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).


         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).


         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


         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).


         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).


         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).


         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).


         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.


    Level causing no toxicological effect

     Rat:     0.5% (=5000 ppm) in the diet equivalent to 250 mg/kg body

    Estimate of temporary acceptable daily intake for man

    0-1.25 mg/kg body weight.


    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


         Information on the pharmacokinetics of erythrosine and its effect
    on the thyroid functions of human subjects.


    B.W. (1981) Three generation reproduction study. Unpublished report
    from International Research and Development Corporation, Mattawan,
    Michigan, USA, submitted to the World Health Organization by the
    Certified Color Manufacturers Association Inc., Washington, D.C., USA.

    ANDERSEN, C.J., KEIDING, N.R., & NIELSON, A.B. (1964) False elevation
    of serum protein-bound-ikodine caused by red colored drugs or foods.
    Scand. J. Clin. Lab. Inrest., 16: 249.

    ANONYMOUS (1969) Studies attributed to the United States Food and Drug
    Administration as unpublished report. Reference and Summary reported
    in WHO Food Additives Series No.6, 1975, p.80.

    AULETTA, A.E., KUZAVA, J.M., & PARMAR, A.S. (1977) Lack of mutagenic
    activity of a series of food dyes for Salmonella typhimurium.
    Mutation Research, 56: 203.

    BAR, F. & GRIEPENTROG, F. (1960) Die Allergenwirkung von Frenden
    Stoffen in den Lebensmitteln. Med. U. Ernaehr, 1: 99-104.

    BERNSTEIN, R., HAUGEN, H.F., & FREY, H. (1975) Thyrolid function
    during erythrosine ingestion in doses encountered in therapy with
    conventional antibiotics. Scand. J. Clin. Lab. Inrest., 35: 49.

    BONIN, A.M. & BAKER, R.S.U. (1980) Mutagenicity testing of some
    approved food additives with Salmonella microsome assay. Fd. Tech.
    Aust., 32(12): 608.

    BOWIE, W.C., WALLACE, W.C., & LINDSTROM, H.V. (1966) Some clinical
    manifestations of erythrosine in rats. Fed. Proc., 25:556
    (Abstract 2079).

    (1981) Long-term dietary toxicity/carcinogenicity study in rats.
    Unpublished report from International Research and Development
    Corporation, Mattawan, Michigan, USA, submitted to the World Health
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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)