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Administrative data

Endpoint:
repeated dose toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Review by a recognised source.

Data source

Referenceopen allclose all

Reference Type:
review article or handbook
Title:
Unnamed
Year:
2001
Reference Type:
publication
Title:
Toxicity and carcinogenicity of potassium bromate--a new renal carcinogen.
Author:
Kurokawa Y; Maekawa A; Takahashi M; et al.
Year:
1990
Bibliographic source:
Environ Health Perspect 87:309-335, 1990. Cited in EPA 2001.
Reference Type:
publication
Title:
(1989) Renal changes induced by chronic oral administration of potassium bromate or ferric nitrilotriacetate in Wistar rats.
Author:
Nakano, K; Okada, S; Toyokuni, S; et al.
Year:
1989
Bibliographic source:
Jpn Arch Intern Med 36:41-47, 1989. Cited in EPA 1989.

Materials and methods

Principles of method if other than guideline:
A review of existing data.
The investigations were performed with potassium bromate. A read across to sodium bromate is justified as both substances dissociated in water and Na+ and K+ ions are naturally occurring species.
GLP compliance:
not specified

Test material

Constituent 1
Reference substance name:
Potassium bromate.
IUPAC Name:
Potassium bromate.
Constituent 2
Reference substance name:
Potassium bromate
EC Number:
231-829-8
EC Name:
Potassium bromate
Cas Number:
7758-01-2
IUPAC Name:
potassium bromate
Constituent 3
Reference substance name:
Bromic acid, potassium salt
IUPAC Name:
Bromic acid, potassium salt

Results and discussion

Results of examinations

Details on results:
The subchronic effects of bromate were evaluated by Kurokawa et al. (1990), who administered potassium bromate in water at concentrations of 0, 150, 300, 600, 1,250, 2,500, 5,000, or 10,000 ppm to groups of F344 rats (10/sex/group) for 13 weeks. Assuming average default drinking water consumption of 0.4 L/day and an average default body weight of 0.3 kg, the authors calculated doses corresponding to these concentrations as about 0, 16, 32, 63, 140, 270, 650, or 1,080 mg BrO3-/kg and day. All animals exposed to >1,250 ppm died within 7 weeks. Observed signs of toxicity included significant inhibition of body weight gain in males at 600 ppm or above and significant increases of serum parameters (glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, lactate dehydrogenase, alkaline phosphatase, blood urea nitrogen [BUN], Na+, and cholinesterase) in both sexes at 600 ppm. Serum potassium levels were significantly decreased. Droplets of various sizes and regenerative changes in the renal tubules were observed. This study identifies 63 mg BrO3-/kg and day as an adverse effect level, but insufficient data were provided to determine whether effects occurred at lower doses.

Nakano et al. (1989) exposed male Wistar rats to 0.04% potassium bromate in drinking water for up to 15 months. At an intake of 0.1 L/kg.day, this corresponds to a dose of about 30 mg BrO3-/kg.day. Body weight gain was markedly inhibited in the exposed animals. Histological examination of kidneys at 7–11 weeks revealed karyopyknotic foci (a necrotic change characterized by shrinking of the nucleus and condensation of the chromatin) in tubules of the inner medulla. Increased BUN was noted after 15 months, along with marked structural abnormalities of the cortical tubules. On the basis of the decreased body weight gain and renal effects, this study identified a lowest-observed-adverse-effect-level (LOAEL) of 30 mg BrO3-/kg.day, but did not identify a no-observed-adverse-effect-level (NOAEL).

Effect levels

open allclose all
Dose descriptor:
LOAEL
Effect level:
<= 63 mg/kg bw/day (nominal)
Based on:
other:
Sex:
male/female
Basis for effect level:
other: Result of a 13 weeks toxicity study with rats.
Dose descriptor:
LOAEL
Effect level:
30 mg/kg bw/day (nominal)
Based on:
other: bromate (BrO3-)
Sex:
male
Basis for effect level:
other: From a 15 months toxicity study with rats.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Executive summary:

A 13 weeks toxicity study with rats was performed by dosing the animals with potassium bromate in the drinking water.

The LOAEL was below 63 mg BrO3-/kg bw/day.

A 15 months toxicity study with male rats was performed by dosing the animals with potassium bromate in the drinking water. The LOAEL was 30 mg BrO3-/kg bw/day.