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    POTASSIUM BROMATE

    Explanation

         Potassium bromate has been evaluated for acceptable level of
    treatment for flour to be consumed by man by the Joint FAO/WHO
    Committee on Food Additives in 1964 (Annex I, Ref. 7). In addition to
    its use in the treatment of flour, potassium bromate is used in
    treating barley in beer making and it has been used for the
    improvement of the quality of fish-paste products in Japan (Ministry
    of Health and Welfare, Japan, 1979).

         Since the previous evaluation, additional data have become
    available. The previously published monograph is reproduced in its
    entirety below and has been expanded to include summaries of new
    studies which have become available.

    BIOLOGICAL DATA

    BIOCHEMICAL ASPECTS

    Effects of baking on potassium bromate-treated flour

         When potassium bromate was present in flour at levels of
    5-80 mg/kg, no residual bromate was detectable in bread prepared from
    the flour by a bulk-fermentation process after 20-25 minutes baking
    (Bushuk & Hlynka, 1960).

         Potassium bromate present in flour at 30 mg/kg was quantitatively
    converted to bromide in bread prepared from the flour by a bulk-
    fermentation process (Lee & Tkachuk, 1960).

         Bread was made by bulk fermentation and also by mechanical
    development from flour doughs containing 0-200 mg/kg potassium bromate
    and the amount of residual bromate in the bread was determined. When
    the added potassium bromate was 50 mg/kg or less, no residual
    potassium bromate could be detected; at higher levels of addition,
    increasing amounts of residual potassium bromate were detected, bulk
    fermentation giving higher residual levels than mechanical development
    (Thewlis, 1974).

    Effects on nutritional value

         Treatment of flour with potassium bromate at a concentration of
    45 mg/kg did not cause any decrease in its content of thiamine,
    riboflavin or nicotinic acid (Ford et al., 1959). Wheat flours treated
    with potassium bromate at a concentration of 25 mg/kg and stored for
    12 months did not show any greater decrease in tocopherol content than
    flour, either untreated or treated with ascorbic acid, stored under
    the same conditions (i.e. not more than 35-50%) (Menger, 1957).

         At high levels of use, about 200 mg/kg, bromate has no
    significant effect on the thiamine, riboflavin or nicotinic acid
    content of flour or of bread made from it. No statistically
    significant differences have been found in essential fatty acid
    content in flour treated with 200 mg/kg potassium bromate or in bread
    made from such flour (Ministry of Agriculture, Fisheries and Food, UK,
    1974).

         Potassium bromate completely destroys folic acid in solution in
    10 days (British Food Manufacturing Industries Research Association,
    1980).

    TOXICOLOGICAL STUDIES

    Studies on bromate-treated flour and bread

    Short-term studies

    Rat

         Bread made from flour treated with 14 mg/kg and with 100 mg/kg of
    potassium bromate was fed to two groups of six male and 20 female rats
    each and these diets continued over three generations, the entire
    experiment lasting 10 months. The health, behaviour, weight gain and
    reproductive performance remained normal throughout. Histological
    study of the tissues showed no abnormalities and analyses of brain and
    liver showed no accumulation of bromine.

         Eighteen rats were fed a diet containing 84% of flour treated
    with potassium bromate at a level of about 75 mg/kg for a period of
    four weeks. Growth and reproductive performance were normal.

         Bread made from flour treated with 200 mg/kg of potassium bromate
    was fed to 12 rats for 16 days and the flour itself to 16 rats for 10
    weeks without adverse effects (Ford et al., 1959).

    Dog

         Three dogs were fed for 12 weeks a diet containing 84% of bread
    made from flour treated with 75 mg/kg potassium bromate. No ill-
    effects were observed. Five dogs were fed for six to 14 weeks flour
    treated at a level of 75 mg/kg potassium bromate. Two dogs were fed
    for 16 days with bread made from flour treated at a level of 200 mg/kg
    with potassium bromate. No ill-effects were observed (Ford et al.,
    1959).

         Three dogs fed for six weeks on diets containing flour treated
    with 70 mg/kg potassium bromate showed no ill-effects or "running
    fits". Four dogs fed for 17 months on bread made from flour containing
    200 mg/kg potassium bromate showed no adverse effects attributable to
    the diet (Impey et al., 1961).

    Monkey

         Three monkeys fed for eight weeks on a diet containing 84% of
    bread made from flour treated with 75 mg/kg potassium bromate showed
    no adverse effects (Ford et al., 1959).

    Long-term studies

    Mouse

         Groups of mice fed flour treated with 15 mg/kg potassium bromate
    showed no ill-effects over eight generations (Ford et al., 1959).

         Groups of 60 male and 60 female mice were fed for 80 weeks on
    five diets containing 79% breadcrumbs; the bread used was prepared
    from untreated flour (control), from flour treated with 50 mg/kg or
    75 mg/kg potassium bromate, or from flour treated with 50 mg/kg
    bromate plus one of two mixtures of other commonly used flour
    additives (ascorbic acid, benzoyl peroxide and chlorine dioxide).
    Appearance, behaviour, health and survival were similar in test and
    control groups and there was no evidence that any of the treatments
    affected the incidence of neoplasms, the incidence of malignant
    tumours being similar in control and test groups. Anaemia was observed
    in males of all groups (including controls) and in females at 18
    months. No dose-related differences in blood biochemistry were found
    in male mice; in the females, dose-related increases in blood glucose
    levels were observed at one and 12 months but not at 18 months. Renal
    concentration and dilution tests, and urinalysis were indicative of
    normal renal function. Some dose-related differences in the weights of
    heart, pituitary and uterus were found but, when expressed relative to
    body weight, the values for heart and uterus were not dose related.
    The relative weights of pituitary, brain, kidneys and thyroid showed
    dose-related changes in males only, with relative weights of heart and
    pituitary being lowered and kidneys and thyroid elevated. These
    changes were not associated with any histopathological abnormalities.
    No significant dose-related accumulation of covalently-bound bromine
    was observed in adipose tissue (Ginocchio et al., 1979).

    Rat

         Twenty rats were fed for two years with flour treated at a level
    of 627 mg/kg potassium bromate. Weight gain, general health and
    survival rate were not significantly different from those of controls.

         Five generations of rats were fed bread made from flour treated
    with potassium bromate at a level of 15 mg/kg. No effects on weight
    gain, reproductive performance or survival were observed (Ford et al.,
    1959).

         Five groups of 60 male and 60 female rats were fed for 104 weeks
    on five diets containing 79% breadcrumbs; the bread was prepared from
    untreated flour (control), from flour treated with 50 mg/kg or

    75 mg/kg potassium bromate, or from flour treated with 50 mg/kg
    bromate plus one of two mixtures of other flour additives. Appearance,
    behaviour and health were similar in test and control groups. The
    death rate was lower in the test groups than in controls in the
    females and the males of the high-dose group had fewer deaths than the
    other groups taken together. No evidence of carcinogenicity nor of
    chronic toxicity was attributable to the compounds under test at the
    dose levels used. There was no evidence of accumulation of covalently-
    bound bromine in the adipose tissue (Fisher et al., 1979).

    Studies on potassium bromate

    Special studies on carcinogenicity

    Mouse

         A 78-week carcinogenicity study was performed on female B6C3F1
    mice given potassium bromate at concentrations of 500 or 1000 mg/litre
    in drinking-water. No carcinogenic effect was detected (Takayama,
    1982).

    Rat

         Groups of 53 male and 53 female F-344 rats were given potassium
    bromate in drinking-water at concentrations of 0, 250 and 500 mg/litre
    for 110 weeks, except that the high concentration was reduced to
    400 mg/litre for male rats in week 60 due to severe inhibition of body
    weight gain. Animals dying or moribund in the course of the study were
    autopsied immediately; survivors were killed and autopsied at week 111
    and a detailed histopathological examination was carried out,
    including 10-15 step serial sections on the kidneys.

         The mean survival time was shortest in males given 500 mg/litre
    potassium bromate (88.1 ± 18.1 weeks); the mean survival times of the
    other groups were between 101 and 104 weeks. Renal tubules in
    potassium bromate-treated rats showed various pathological changes;
    degenerative, necrotic and regenerative changes were very common. All
    the male animals bore tumours (including controls) and tumour
    incidence was very high in females (85, 92 and 83% in females
    receiving 0, 250 and 500 mg/litre potassium bromate, respectively).
    However, the incidence of tumours of the kidney, peritoneum and
    thyroid was statistically significantly higher in treated animals than
    in controls. Tumours (adenocarcinomas and adenomas) of the kidney
    developed in 6, 50 and 85% of males and 0, 40 and 63% of females
    receiving 0, 250 and 500 mg/litre respectively. The incidence of
    mesotheliomas of the peritoneum was 11, 32 and 54% in male rats given
    0, 250 and 500 mg/litre respectively, but there was zero incidence of
    this type of tumour in females, either treated or controls. Induction
    times for renal cell tumours were relatively long, the shortest being
    14 weeks (male, 500 mg/litre).

         It was concluded by the authors that potassium bromate was
    carcinogenic in Fisher 344 rats by oral administration (Kurokawa et
    al., 1982a,b; Kurokawa, 1982).

    Special studies on mutagenicity

         Potassium bromate was reported to give positive results for
    mutagenicity in the Ames test, chromosome aberration test and
    micronucleus test but gave negative results in the rec-assay and in a
    silk-worm assay (Kawachi et al., 1980; Ishidate et al., 1981).

    OBSERVATIONS IN MAN

         A number of case studies of acute human intoxication with
    potassium bromate have been reported following accidental ingestion or
    attempted suicide. In autopsy cases, degeneration of kidney tubules
    and liver parenchymal cells, and acute myocarditis were the principal
    pathological changes observed (Paul, 1966; Stewart, 1969; Niwa et al.,
    1974; Norris, 1965; Quick et al., 1975).

    Comments

         Neither short- nor long-term feeding with flour treated with high
    levels of potassium bromate or with bread made from it revealed any
    adverse effects and, at the level of use for technological treatment
    of flour, bromate is converted to bromide; low or undetectable
    residues remain in bread prepared from treated flours. Bromate used in
    treating barley in beer making is similarly reduced to bromide.
    Somewhat higher (not specified) residues of bromate have been claimed
    to occur in bromate-treated fish-paste (Oikawa & Saito, 1982).

         Insufficient is known of the fate of bromate in commodities other
    than baked flour products to establish an estimate of acceptable level
    of treatment.

         The Committee considered that bromate as such should not be
    present in food as consumed; therefore, the use of potassium bromate
    could only be approved when such usage resulted in negligible
    residues. The main toxicological consideration that then arises is
    concerned with the maximum tolerable daily intake of bromide. Many
    foods have a natural content of bromine, as Br-, in the range
    1-10 mg/kg (Blaignan, 1932; Damiens & Blaignan, 1931, 1932; Viggiano &
    Turk, 1937) and some foods contain considerably more; flour itself has
    a natural bromine content of 2.4-7.7 mg/kg. The Committee considered
    that the maximum tolerable daily intake of bromide should be dealt
    with at a subsequent meeting.

    EVALUATION

    Level causing no toxicological effect

    Rat:      Flour treated at levels of 15, 50, 75 and 100 mg/kg was well
              tolerated.

    Estimate of acceptable level of treatment of foods to be consumed by
    man

    For flour:          Temporary acceptance 0-75 mg/kg flour (providing
                        that bakery products prepared from such treated
                        flour contain negligible residues of potassium
                        bromate).

    For other food      No acceptable level of treatment allocated.

    FURTHER WORK OR INFORMATION

    Required by 1985

         Further studies to establish the residual levels of potassium
    bromate in foods treated with it.

    REFERENCES

    Blaignan, S. (1932) Contribution à l'étude du brome normal dans la
         regne végétal. Thesis, Paris

    British Food Manufacturing Industries Research Association (1980)
         Annual report, p. 29

    Bushuk, W. & Hlynka, I. (1960) Cereal Chem., 37, 573

    Damiens, A. & Blaignan, S. (1931) C.R. Acad. Sci. (Paris), 193,
         1460

    Damiens, A. & Blaignan, S. (1932) C.R. Acad. Sci. (Paris), 194,
         2077

    FAO/WHO (1964) Specifications for the identity and purity of food
         additives and their toxicological evaluation: emulsifiers,
         stabilizers, bleaching and maturing agents (Seventh report of the
         Joint Expert Committee on Food Additives). FAO Nutrition Meetings
         Report Series, No. 35, 1964; WHO Technical Report Series, No.
         281, 1964

    Fisher, N. et al. (1979) Long-term toxicity and carcinogenicity
         studies of the bread improver potassium bromate. 1. Studies in
         rats, Food Cosmet. Toxicol., 17, 33-39

    Ford, W. P., Kent-Jones, D. W. & Frazer, A. C. (1959) Unpublished
         submission, dated 8 December 1959, to the Preservatives
         Sub-Committee of the United Kingdom Food Standards Committee,
         Appendices I-IV

    Ginocchio, A. V. et al. (1979) Long-term toxicity and carcinogenicity
         studies of the bread improver potassium bromate. 2. Studies in
         mice, Food Cosmet. Toxicol., 17, 41

    Impey, S. G., Moore, T. & Sharman, I. M. (1961) J. Sci. Fd. Agric.,
         11, 729

    Ishidate, M., Sofuni, J. & Yoshikawa, K. (1981) Chromosomal aberration
         tests in vitro as a primary screening tool for environmental
         mutagens and/or carcinogens, Gann Monograph on Cancer Research,
         27, 95

    Kawachi, T. et al. (1980) In: Williams, G. M., ed., The predictive
         value of short-term screening tests in carcinogenicity
         evaluation, Amsterdam, Elsevier, pp. 253-267

    Kurokawa, Y. (1982) Communication submitted to WHO

    Kurokawa, Y. et al. (1982a) Induction of renal cell tumors in F-344
         rats by oral administration of potassium bromate, A Food
         Additive. Gann, 73, 335

    Kurokawa, Y. et al. (1982b) Carcinogenicity of potassium bromate by
         oral administration to F-344 rats. Report submitted to WHO by
         Y. Kurokawa

    Lee, C. C. & Tkachuk, R. (1960) Cereal Chem., 37, 575

    Menger, A. (1957) Brot und Geback, 11, 167

    Ministry of Agriculture, Fisheries and Food, UK (1974) Standards
         Committee Second Report on Bread and Flour, FSC/REP/61 H.M.S.O.

    Ministry of Health and Welfare, Japan (1979) The Japanese standards of
         food additives, 4th Ed., p. 367

    Niwa, T., Ho, T. & Matsui, E. (1974) Serial renal biopsy in potassium
         bromate intoxication, Jap. Circ. J., 38, 387

    Norris, J. A. (1965) Toxicity of home permanent waving and neutralizer
         solutions, Food Cosmet. Toxicol., 3, 93-97

    Oikawa, K. & Saito, H. (1982) Unpublished data cited from Kurokawa et
         al. (1982)

    Paul, A. H. (1966) Chemical food poisoning by potassium bromate,
         N.Z. Med. J., 65, 33

    Quick, C. A., Chole, R. A. & Mauer, S. M. (1975) Deafness and renal
         failure due to potassium bromate poisoning, Arch. Otolaryngol.,
         101, 494

    Stewart, T. H., Sherman, Y. & Politzer, W. M. (1969) An outbreak of
         food poisoning due to a flour improver, potassium bromate, S.A.
         Med. J., 43, 200

    Takayama, S. (1982) Unpublished results cited from Kurokawa et al.
         (1982)

    Thewlis, B. H. (1974) The fate of potassium bromate when used as a
         breadmaking improver, J. Sci. Fd. Agric., 25, 1471

    Viggiano, J. & Turk, E. F. H. (1937) Analyst, 62, 559
    


    See Also:
       Toxicological Abbreviations
       Potassium bromate (ICSC)
       Potassium bromate (WHO Food Additives Series 24)
       Potassium bromate (WHO Food Additives Series 30)
       POTASSIUM BROMATE (JECFA Evaluation)
       Potassium Bromate  (IARC Summary & Evaluation, Volume 40, 1986)