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    CARBON BLACK

    EXPLANATION

         Activated carbon (synonyms, activated charcoal and decolorizing
    carbon), that is carbon black derived from vegetable material or
    lignites, was evaluated under the name "activated vegetable carbon
    (food grade)" at the fourteenth meeting of the Committee (Annex 1,
    reference 22). An ADI "not limited", except that good manufacturing
    practice be followed, was established. This refers to its use as a
    clarifying agent, not as a food colour. A toxicological monograph was
    published (Annex 1, reference 23), and new data evaluated at the
    present meeting are included in this monograph addendum.

    BIOLOGICAL DATA

         Four recent reviews have been published on carbon black
    (NCI, 1985; IARC, 1984; Rivin & Smith, 1982; NIOSH, 1978).

    Biochemical aspects

    Absorption, distribution, and excretion

         Inhaled carbon black is retained in the lungs. Clearance is by
    macrophage uptake, retrograde mucociliary movement, and possibly
    secondary gastrointestinal ingestion. Absorption into the blood stream
    for systemic distribution evidently does not occur. There have been no
    reports of gastrointestinal absorption and carbon black is probably
    cleared in the faeces (Nau et al., 1962, 1976; NCI, 1985).

    Toxicological studies

    Special studies on the bioavailability of polynuclear hydrocarbons
    adsorbed on carbon blacks

    In vitro studies

         Samples of 3 different carbon blacks (rubber-grade oil furnace
    blacks, ASTM designation N-234, N-351, and N-375) were extracted with
    the following tissue fluids and cellular components: human plasma,
    swine serum, the supernatant of swine lung homogenates, and swine lung
    washings. All tissue fluids were poor eluters of benzo(a)pyrene (less
    than 0.005% of the absorbed benzo(a)pyrene content of the carbon black
    as determined by toluene extraction was extracted by the tissue
    fluids). Swine serum was a less efficient extractant than human
    plasma. Swine lung homogenate and lung washings were equally effective
    (Buddingh et al., 1981).

         The extent of the elution of benzo(a)pyrene depends on the
    benzo(a)pyrene content of the carbon black and surface area of the
    particles, e.g. soot particles of 100 nanometers or less adsorb free
    benzo(a)pyrene from a protein medium (Falk & Steiner, 1952).

    In vivo studies

         Groups of 5 male and 5 female outbred CIGR mice were fed diets
    containing 0, 0.0082, 0.20, or 2.0% of 3 different carbon blacks
    (N-234, N-351 and N-371) for 3 successive generations. Litters from
    the F0, F1, and F2 generations were killed at day 28, breeders
    from the F2 generation were killed, and arylhydrocarbon hydroxylase
    activities of the liver and lungs were determined. Dietary exposure to
    carbon black had no effect on enzyme activity, suggesting that the
    elution of benzo(a)pyrene was not sufficient to induce increased
    enzyme activity in this system (Buddingh et al., 1981).

    Special studies on carcinogenicity

    Mice

         Groups of 10-50 CFW white and/or CH3 brown mice in a series of
    feeding experiments were administered, for periods of 12 to 18 months,
    either: (1) 10% carbon black; (2) 10% benzene-extracted carbon black;
    (3) benzene extract from carbon black; (4) 3-methyl-cholanthrene (MCA)
    or MCA adsorbed to flour; or (5) MCA adsorbed to benzene-extracted
    carbon black. The test material was dispersed in the basal diet by use
    of either a water-base mixture containing carboxy-methyl cellulose or
    an oil-base mixture containing cotton seed oil. For the control
    groups, the basal diet was supplemented with either the water-base
    mixture or oil-base mixture. At termination of the study, all the mice
    were killed and complete gross and microscopic examinations were made
    of all organs and tissues. No significant effects were observed in
    either the control groups or the groups given the unextracted carbon
    black. Mice fed extracted carbon black in the water-base diet
    developed a number of rumours (10/100). Nine of these tumours
    (3 intracutaneous fibrosarcomas, 3 begnin squamous papillomas, and 3
    squamous metaplasas with malignancy) were considered to be due to
    benzene-extractive material that had not been completely removed from
    the benzene-extracted carbon black. No significant effects were
    reported in the group fed extracted carbon black in the oil-base
    mixture. Mice fed the benzene extract of carbon black in diets
    containing either the water-base or oil-base mixture developed tumours
    of the gastrointestinal tract and carcinomas of the stomach. In the
    groups of mice fed MCA, there was a high incidence of adenocarcinomas
    or squamous-cell carcinomas of the gastrointestinal tract. However, in
    the groups of mice fed MCA that was adsorbed to extracted carbon
    black, only 1 of 190 developed fibrosarcoma of the gastrointestinal
    tract (Nau et al., 1958).

    Mice and rats

         Groups of 24 or 48 Swiss mice or Harlan stock rats were
    administered, for more than 15 months, *para-dimethylaminoazobenzene
    (DMAB), methyl cholanthrene, or 3,4-benzo(a)pyrene, either free or
    adsorbed onto various carbon blacks; carbon black alone was
    administered to other groups of mice and rats. The level of carbon
    black in the diet ranged from 9 to 18%. All animals were killed and
    necropsied, and selected tissues were examined histologically. No
    tumours were observed in the groups of mice or rats receiving carbon
    black only. In the group receiving free DMAB, 14/24 mice (58%)
    developed hepatic tumours. Of the groups receiving DMAB adsorbed onto
    carbon black, only one group developed tumours. The time to first
    rumour in this group was 10.25 months compared to 6 months in positive
    controls. None of the other groups treated with the adsorbed

    carcinogens developed rumours, although high incidences were observed
    in the test animals fed the carcinogens alone. Test animals treated
    with acetone suspensions of carbon black plus 3,4-benzo(a)pyrene
    developed a high incidence of tumours (54-69%); however, the onset of
    rumours was delayed when compared to positive controls
    (von Haam et al., 1958).

         Groups of female 26-31 CF1 mice and female 29-45 Sprague-Dawley
    rats were fed either 0 or 2.0 g carbon black (ASTM N-375) per kg of
    ground lab chow diet for 2 years. This dietary level was calculated to
    amount to an average consumption of 100 g/kg b.w./year for the mice
    and 38 g/kg b.w./year for the rats. (The average fat content of this
    rodent chow was later reported by these authors (1986) to be
    approximately 5% by weight.) Simultaneously, groups of mice and rats
    were exposed to carbon black for 52 weeks with or without the
    administration of 1,2-dimethylhydrazine (DMH) via 16 weekly i.p.
    injections at dose levels of 10 mg/kg b.w. in rats and 20 mg/kg b.w.
    in mice. Control animals were given the solvent (lmM EDTA) by
    injection. After 52 weeks or 2 years, the animals were killed, gross
    necropsies performed, and all lesions examined microscopically. The
    survival of all groups of animals was comparable; there was no
    apparent effect of carbon black ingestion on tumour incidence. A small
    non-significant incidence in colon tumours was seen in the group not
    treated with DMH in the 2-year study. In the 52-week groups in which
    carbon black plus DMH was administered, there were no enhancements in
    gastrointestinal, respiratory, mammary, or urinary tumours. However,
    groups given carbon black and DMH had an increased mortality (Pence &
    Buddingh, 1985).

    Rats

         Groups of 25 female Sprague-Dawley rats were administered carbon
    black (ASTM N-375) at a level of 0 or 2.0 g/kg diet. The study
    utilized a high-fat diet and consisted of 20% (w/w) corn oil added to
    a ground commercial chow diet. The average carbon black consumption
    was calculated to be 38 g/kg b.w./year. Colonic tumours were induced
    in the test groups by 16 weekly i.p. injections of DMH at 10 mg/kg
    b.w. All groups were maintained on test diets for 52 weeks, killed,
    subjected to necropsy, and all lesions were examined microscopically.
    Weight gain and food intake were not affected by any of the four
    regimens. DMH-treated rats had decreased survival due to intestinal
    tumours, and this effect was most prominent in the group also
    receiving carbon black. There were no colonic tumours in animals not
    treated with DMH. In the DMH group maintained on a high-fat diet, 60%
    of the females had colonic tumours. This was significantly different
    (P < 0.05) from the 76% seen in the DMH group maintained on the same
    high-fat diet which contained 2.0 g/kg carbon black (Pence & Buddingh,
    1986).

    Special studies on mutagenicity

         Commercially produced furnace carbon black (rubber grade, CAS
    No. 1333-86-4) containing 194 ppm polynuclear aromatic hydrocarbons
    (PAHs) (determined on a benzene extract) showed limited toxicity but
    no mutagenetic activity in the following assays; (1) Salmonella
    assay, 5 tester strains of Salmonella typhimurium (TA98, TA100,
    TA1535, TA1537 and TA1538), with or without metabolic activation, at
    levels up to 7,500 µg/plate; (2) sister-chromatid exchange in Chinese
    hamster ovary cells, with or without metabolic activation, at test
    levels up to 1000 µg/ml; (3) mouse lymphoma cell L5178 assay, with or
    without metabolic activation, at test levels up to 15,000 µg/ml; (4)
    C3H/10 T1/2 cell transformation assay at test levels up to
    16,384 µg/ml; and (5) the Drosophila assay (Kirwin et al., 1981).

    Short-term studies

    No information available.

    Long-term studies

    Mice

         Groups of 8-week old C3H mice were fed diets containing either
    0 or 10% thermal black for as long as 72 weeks. No significant gross
    or microscopic changes from normal were seen. This was a summary
    report and did not give any details (Nau et al., 1976).

    Observations in man

         No reports on oral ingestion of carbon black by humans were
    available. The available information relates to occupational exposure
    through inhalation. Three reviews have been published which examined
    the toxicity of carbon black to humans under these conditions
    (NIOSH, 1978; Rivin & Smith, 1982; IARC, 1984).

         The major effect of carbon black in humans is on lung function.
    Other effects in humans attributed to carbon black are dermatological
    lesions, skin irritation, acute gastrointestinal diseases, myocardial
    dystrophy, and cardiovascular changes. In both of the reports on heart
    effects, there was concomitant exposure to carbon monoxide (Komarova,
    1965, 1973, as cited by NIOSH, 1978).

         IARC (1984) reviewed the available epidemiological data and
    concluded that the data provide inadequate evidence to evaluate the
    carcinogenicity of carbon black to humans.

    COMMENTS

         Carbon black used for colouring purposes falls within two main
    groups, those derived from hydrocarbons and those derived primarily
    from peat and plant materials, commercially described as vegetable
    black.

         The food colouring uses of carbon blacks derived from both
    sources were evaluated by the Committee at the twenty-first meeting
    (Annex 1, reference 44). No ADI was established for food colouring
    uses from either source. A major concern of that Committee related to
    the question as to how strongly and irreversibly PAHs are adsorbed
    onto carbon black.

         The present Committee considered data from studies involving
    carbon black prepared from hydrocarbon sources. Benzene extracts of
    certain carbon blacks were found to be carcinogenic to mice. These
    carcinogenic extracts contain PAHs adsorbed to carbon black. Data were
    available to show that only small amounts of PAHs (less than 0.005% of
    the benzene-extractable PAHs) were eluted from carbon black by
    biological fluids. Carbon black was not mutagenic in bacterial or
    mammalian systems. Dietary carbon black was not carcinogenic in
    limited lifetime studies in rats and mice at levels up to 10% of the
    diet. Information was also presented to show that carbon black was
    able to adsorb some chemical carcinogens and, under certain
    experimental conditions, was shown to reduce their carcinogenic
    potential.

         No toxicological data were available on carbon black derived from
    vegetable sources.

    EVALUATION

    Carbon black (hydrocarbon sources)

    Food contact materials

         The use of carbon black from hydrocarbon sources is provisionally
    accepted in food contact materials, including wax coatings for cheese.
    Future specifications should include figures relating to residual
    PAHs.

    Direct use in food

         No ADI could be established (a) because carbon blacks from
    hydrocarbon sources have been shown to contain different amounts of
    known carcinogens and knowledge is lacking on the ability of man to
    extract such carcinogens upon ingestion and (b) because of limited
    feeding studies in experimental animals with defined carbon blacks.

    Carbon black (vegetable black)

         No ADI could be established because no toxicological data were
    available.

    REFERENCES

    Buddingh, F., Bailey, M.J., Wells, B., & Haesemeyer, J. (1981).
    Physiological significance of benzo(a)pyrene adsorbed to carbon
    blacks: Elution studies; AHH determinations. Amer. Ind. Hyg.
    Assoc. J., 42, 503-509.

    Falk, H.L. & Steiner, P.E. (1952). The adsorption of 3,4-benzpyrene
    and pyrene by carbon blacks. Cancer Res., 12, 40-43.

    von Haam, E., Titus, H.L., Caplan, I., & Shinowara, G.Y. (1958).
    Effect of carbon blacks on carcinogenic compounds. Proc. Soc. Exptl.
    Biol. Med., 98, 95-98.

    IARC (1984). Monographs on the evaluation of the carcinogenic risk of
    chemicals to humans. International Agency for Research on Cancer.
    WHO/IARC Monograph, vol. 33, pp. 35-85.

    Kirwin, C.J., Le Blanc, J.V., & Thomas, W.C. (1981). Evaluation of the
    genetic activity of industrially-produced carbon black.
    J. Tox. Environ. Health, 7, 973-989.

    Nau, C.A., Neal, J., & Stembridge, V.A. (1958). A study of the
    physiological effects of carbon black - I. Ingestion. A.M.A. Arch.
    Ind. Health, 17, 21-28.

    Nau, C.A., Neal, J., Stembridge, V.A., & Cooley, R.N. (1962).
    Physiological effects of carbon black - IV. Inhalation.
    Arch. Environ. Health, 4, 415-431.

    Nau, C.A., Taylor, G.T., & Lawrence, C.H. (1976). Properties and
    physiological effects of thermal carbon black. J. Occup. Med.,
    18, 732-734.

    NCI (1985). Monograph on human exposure to chemicals in the workplace:
    Carbon black. National Cancer Institute. NTIS publication
    No. PB86-152048, Springfield, VA, USA.

    NIOSH (1978). Criteria for a recommended standard. Occupational
    exposure to carbon black. National Institute for Occupational Safety
    and Health. DHEW publication No. 78-204. US Department of Health,
    Education and Welfare, Washington, DC 20204, USA.

    Pence, B.C. & Buddingh, F. (1985). The effect of carbon black
    ingestion on 1,2-dimethylhydrazine induced colon carcinogenesis in
    rats and mice. Tox. Letters, 25, 273-277.


    Pence, B.C. & Buddingh, F. (1986). Co-carcinogenesis effect of carbon
    black ingestion with dietary fat on the development of colon tumours
    in rats. Manuscript submitted to Tox. Letters, September, 1986.

    Rivin, D. & Smith, R.G. (1982). Environmental health aspects of carbon
    black. Rubber Chem. Technol., 55, 707-761.
    


    See Also:
       Toxicological Abbreviations
       Carbon black (ICSC)
       Carbon Black (IARC Summary & Evaluation, Volume 65, 1996)