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

    CHOCOLATE BROWN FB

    Explanation

         This material is known to be a complex mixture of dyes. The
    Committee was unable to relate the available toxicological data to a
    substance of defined chemical specifications.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    BIOLOGICAL DATA

    BIOCHEMICAL ASPECTS

         No information available.

    Acute toxicity

                                                                    

                                  LD50
    Animal            Route     (mg/kg bw)       References
                                                                    

    Mouse, male       i.p.    220 (190-250)      Gaunt et al., 1967
    Mouse, female     i.p.    210 (170-250)      Gaunt et al., 1967
    Rat, both sexes   i.p.    Approx. 250-500    Gaunt et al., 1967
                                                                    

    Short-term studies

    Mouse

         Daily intubation of 1000 mg/kg for three weeks gave no signs of
    intoxication (Gaunt et al., 1967).

    Rat

         Daily intubation of 2000 mg/kg gave no signs of intoxication
    (Gaunt et al., 1967).

         No ill effects followed ingestion by three weanling rats of an
    0.1% solution for 28 days, daily intake of the dye was about 15 mg/rat
    (Goldblatt and Frodsham, 1952).

         In a 90-day study in four groups of 32 rats (16 males and
    16 females) given dietary levels of 0, 0.3. 1 and 3% of the dye
    (stated purity 81.8%) no departure from normality was seen with
    respect to food consumption, haematology, liver and kidney function

    and organ weights. A slight, but non-significant retardation of growth
    was noted in males at the 3% level. Pathological examination revealed
    presence of pigment in the Kupffer-cells of the liver at the 3% level,
    and in the alimentary canal, lymph nodes and renal tubules at the 1%
    and 3% levels (Gaunt et al., 1967).

    Pig

         Four groups of three male and three female pigs (large white
    strain) received the dye (stated purity 81.8%) dietary for 16 weeks at
    doses of 0, 25, 250 and 1000 mg/kg body weight/day. There were no
    significant differences between the control and treated groups in body
    weight gain, haematological examinations, urine analyses or organ
    weight, except for a decrease in abs. weight of lungs in the males.
    The effect attributable to treatment was a pigmentation of lymph nodes
    in the pigs of the highest dose groups and in one female given
    250 mg/kg/day; traces of pigment were also detected in some of the
    macrophages in the lymph nodes of two males given 25 mg/kg/day.
    Further pigmentation was detected in the mucosa of the alimentary
    tract and in the lymphoid collections within it, in the pigs of
    the highest dose group. The kidneys of one male pig receiving
    1000 mg/kg/day were dark brown as a result of pigmentation of the
    convoluted tubules (no extensive histopathological study was done)
    (Butterworth et al., 1975).

    Long-term studies

    Mouse

         Five groups of 50 male and 50 female mice (strain CFW) received
    the dye (stated purity 81.8%) dietary for 80 weeks at doses of 0, 300,
    1000, 3000 and 10 000 ppm. There were no dose-related effects on body
    weight gain, haematology or organ weights, though there was a decrease
    in abs. body weight of the males receiving 300 ppm and an increase in
    relative weight of kidneys in the males receiving 300 and 10 000 ppm.
    There was no evidence of any increase in tumour production in mice
    given the dye. Pigment was found in the Kupffer-cells of the liver,
    the phagocytic cells of the lymph nodes and spleen, the alveolar
    macrophages of the lungs and the epithelial cells of the small
    intestine in mice fed on diet containing 10 000 ppm of the dye (Gaunt
    et al., 1973).

    Rat

         Five groups of 30 male and 30 female rats (strain CFE) were fed
    for two years on diets containing 0, 1000, 3000, 10 000 or 30 000 ppm
    of the dye (stated purity 81.8%). No effects attributable to treatment
    were found in mortality, body weight gain, haematology, serum
    chemistry, organ weights (except for a significant increase in
    relative weight of spleen) or incidence of tumours. There was pigment

    deposition in the renal tubular cells at dietary levels of 3000 ppm
    and above. Pigment was also found in Kupffel-cells of the liver and in
    cells of the lymph nodes, spleen and intestinal mucosa of a few female
    rats at the 30 000 ppm level (Gaunt and Brantom, 1972).

    REFERENCES

    Butterworth, K. R., Gaunt, I. F., Grasso, P. and Gangolli, S. D.
    (1976) Short-term toxicity of chocolate Brown FB in pigs, Fd. and
    Cosm. Toxicol., 14, 435-438

    Gaunt, I. F., Hall, D. E., Farmer, M. and Fairweather, F. A. (1967)
    Acute (mouse and rat) and shortterm (rat) toxicity studies on
    chocolate Brown FB, Fd. and Cosm. Toxicol., 5, 159-164

    Gaunt, I. F., Brantom, P. G., Grasso, P. and Kiss, I. S. (1973)
    Longterm toxicity studies of chocolate Brown FB in mice, Fd. and
    Cosm. Toxicol., 11, 375-382

    Gaunt, I. F. and Brantom, P. G. (1972) Longterm feeding study on
    chocolate Brown FB in rats, Fd. and Cosm, Toxicol., 10, 3-15

    Goldblatt and Frodsham (1952) Unpublished report from ICI

    See Also:
       Toxicological Abbreviations
       CHOCOLATE BROWN FB (JECFA Evaluation)