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    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

    WORLD HEALTH ORGANIZATION



    SUMMARY OF TOXICOLOGICAL DATA OF CERTAIN FOOD ADDITIVES
    AND CONTAMINANTS



    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

    BRILLIANT BLACK PN

    Explanation

         This food colour was evaluated by the 1974 and 1977 Joint FAO/WHO
    Expert Committee on Food Additives. Since the previous evaluation,
    additional data have become available and are summarized below.

    BIOLOGICAL DATA

    BIOCHEMICAL ASPECTS

         At concentrations of 2-400 mg/litre the colour inhibits pepsin
    but not lipase (Diemair and Häusser, 1951) and at 12.5 mg/litre it
    inhibits trypsin inconsistently (Diemair and Boeckhoff, 1953).
    Intravenous injection into rabbits and dogs of 50 mg/kg produced only
    small amounts in the urine (Hecht, 1960). Heated in the presence of
    reducing sugars the colour is partially decomposed and gives an orange
    derivative, isolated by paper chromatography, which is the disodium
    salt of 4' (4-sulfo-l-phenylazo) 1' amino 7' sulfonaphthalene (Saenz
    Lascano Ruiz and Laroche, 1960).

         Rats were given brilliant black PN. During the experimental work,
    the faeces and urine of the animals were collected and the presence of
    the dye was noted in faeces and not in the urine. Quantitative
    determination of the dye in the faeces indicated that, from the total
    amount of the dye administered to the rats, 0.6% was excreted in the
    faeces (Piekarski, 1960).

         It has been shown that orally administered brilliant black PN is
    metabolized in the caecum of the rat (Ryan and Welling, 1970), The
    presence of coloured faeces in this study showed that, at the dosage
    levels used, some of the dye passed through the gastrointestinal
    system unchanged. Similar observations were made by Gaunt et al.
    (1967) in rats and Gaunt et al. (1969) in pigs.

    TOXICOLOGICAL STUDIES

    Special studies on mutagenicity

         The colour was tested for mutagenic effect in a concentration of
    0.5 g/100 ml in cultures of Escherichia coli. No mutagenic effect
    was found (Lück and Richeri, 1960).

    Acute toxicity
                                                                        

    Animal         Route     LD50 mg/kg/bw      References
                                                                        

                   Oral      >5 000             DFG, 1957
    Mouse                    >2 000             Gaunt et al., 1967
                   i.p.      550-1 000          Gaunt et al., 1967

                   Oral      >5 000             Gaunt et al., 1967
                             1 100              Gaunt et al., 1967
    Rat            i.p.      >2 000             DFG, 1957

                             2 500
                   i.v.      approximately      DFG, 1957
                                                                        

         Five rats were given 1.5 g/kg bw orally for 22 days. No Heinz
    bodies were found (DFG, 1957). In an experiment with guinea-pigs it
    was found that this colour had no sensitization activity (Bar and
    Griepentrog, 1960). A cat fed 0.1 g/kg bw per day for seven days
    developed no Heinz bodies (DFG, 1957).

    Short-term studies

    Rat
         Groups of 16 male and 16 female weanling rats were fed diets
    containing 0, 0.3, 1.0, and 3.0% colour for 90 days. Growth
    retardation associated with diminished food intake was evident only in
    males at the 3% level. This was shown by a paired feeding test.
    Haematological examination, liver and kidney function tests were
    normal. Organ weight of testes and kidneys increased in males at the
    3% level only. No untoward histopathological findings were seen (Gaunt
    et al., 1967).

    Pig

         Groups of three male and three female pigs were fed black PN
    at dose levels of 0, 100, 300 or 900 mg/kg/day for 90 days. No
    abnormalities in appearance or behaviour were observed. There were no
    consistent or dose-related differences in body weight gain,
    haematology, urinalysis, levels of serum glutamic-oxalacetic and
    glutamic-pyruvic transaminases or organ weights. Haematology and
    urinalysis were conducted at six and 13 weeks while serum
    transaminases were estimated at autopsy. At necropsy no abnormalities
    were observed in control or in the group receiving 100 mg/kg. In one
    female at the 300 mg/kg and in two of each sex at the 900 mg/kg group,
    hard nodules were present in the mucosa of the ileum. Histological

    examination showed that the nodules consisted of collection of cysts
    within the mucus membrane. These cysts were lined by epithelial cells,
    contained mucus and fibrin and were infiltrated with polymorphonuclear
    leucocytes (Gaunt et al., 1969).

    Long-term studies

    Mouse

         Groups of 30 male and 30 female mice were fed diets containing
    0.1, 0.25, 0.5 or 1% (approximately equivalent to 130, 325, 650 or
    1300 mg/kg/day) of black PN for 80 weeks. Groups of 60 mice of each
    sex served as controls. No dose-related effects were observed in
    mortality, body weight gain, haematology, relative organ weights or
    histopathology. The incidence of tumours in the treated mice did not
    exceed that of the control animals (Drake et al. 1977).

    Rat

         Sixteen rats were fed black PN at 0.1% of the diet (average daily
    intake 0.06 g/kg bw) for 410 days and were observed for 761 days. The
    total dose per animal was 5.6 g. One rat died prematurely. No tumours
    were observed (Hecht and Wingler, 1952; DFG, 1957).

         Another group of 10 rats was given 0.5% black PN in their
    drinking-water (average daily intake 0.5 g/kg bw) for 384 days and
    observed 545 days. Total intake per animal was 20 g. No tumours were
    seen (DFG, 1957). In a second experiment, a group of 10 rats was again
    given 0.5% black PN in their drinking-water (average daily intake
    0.45 g/kg bw) for 502 days and observed for 923 days. Total intake per
    animal was 50 g. No tumours were noted (DFG, 1957).

         A group of 10 rats received twice weekly subcutaneously 0.5 ml of
    a 1% solution (approx. 5 mg) for 365 days and was observed for 653
    days. The total amount per animal is 0.5 g. Two animals died
    prematurely but no tumours were noted (DFG, 1957).

         Groups of 24 male and 24 female weanling rats were fed for two
    years on diets containing 0, 1000, 5000 or 10 000 ppm brilliant black
    PN. No effects attributable to treatment were found in respect to
    mortality, food intake, body weight gain, haematology, blood serum
    chemistry, renal concentration tests, organ weights or incidence of
    pathological findings, including tumours (Gaunt et al., 1972).

    REFERENCES

    Bär, F. and Griepentrog, F. (1960) Med. u. Ernähr., 1, 99

    Deutsche Forschungsgemeinschaft (1957) Farbstoff Komission,
    Mitteilung, 6, 58

    Diemair, W. and Häusser, H. (1951) Z. Lebensmitt.-Untersuch., 92,
    165

    Diemair, W. and Boeckhoff, K. (1953) Z. Analyt. Chem., 139, 35

    Drake, J. J. P., Butterworth, K. R., Gaunt, I. F. and Grasso, P.
    (1977) Long-term toxicity study of black PN in mice, Food Cosmet.
    Toxicol., 15, 503

    Gaunt, I. F., Farmer, M., Grasso, P. and Gangolli, S. D. (1967) Acute
    (mouse and rat) and short term (rat) toxicity studies on black PN,
    Food Cosmet. Toxicol., 5, 171

    Gaunt, I. F., Colley, J., Creasey, M. and Grasso, P. (1969) Short term
    toxicity of black PN in pigs, Food Cosmet. Toxicol., 7, 557

    Gaunt, I. F., Campanini, F. M. B., Grasso, P. and Kiss, I. S. (1972)
    Long-term feeding study on black PN in rats, Food Cosmet. Toxicol.,
    10, 17

    Hecht, G. and Wingler, A. (1960) Arzneimittel-Forsch., 2, 192

    Lück, H. and Richerl, E. (1960) Z. Lebensmitt.-Untersuch., 112,
    157

    Piekarski, L. (1960) Roczniki P2H, 11, No. 4, p. 353

    Ryan, A. J. and Welling, P. G. (1970) The metabolism and excretion of
    black PN in the rat and man, Food Cosmet. Toxicol., 8, 487-497

    Saenz Lascano Ruiz, I. and Laroche, C. (1960) Ann. Fals. Exp. Chim.,
    53, 581


    See Also:
       Toxicological Abbreviations
       Brilliant black PN (WHO Food Additives Series 6)
       Brilliant BLACK PN (WHO Food Additives Series 16)
       BRILLIANT BLACK PN (JECFA Evaluation)