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)