Potassium bromate

Endpoint summary

Additional information

Discussion
The genotoxicty of potassium bromate was studied in numerous assays in vitro and in vivo and the results are available in published literature. Summaries of those data have been generated by WHO, IARC and other expert committees. Below a short overview of the data is given that provides key information.
Bromate was mutagenic in Salmonella typhimurium strains (TA100, TA1535 and TA97) and produced chromosomal aberrations in cultured Chinese hamster fibroblast cells  [1, 2]. In assays using V79 Chinese hamster ovary cells, bromate increased the frequency of micronucleated cells, the number of DNA strand breaks and the number of chromosomal aberrations. Furthermore, potassium bromate induced gene mutations in the HPRT locus [3]. Gentox studies using different cell lines and protocols have shown only little or no DNA damage in standard alkaline Comet assays [4].
Positive results were also observed in in vivo studies. Following single oral doses of potassium bromate in Long-Evans rats, the number of aberrant metaphase cells was increased [5], Intraperitoneal injection or gavage dosing in mice leads to elevated numbers of micronuclei with MS/Ae and CD-1 mice strains [6-9]. After intraperitoneal injection of bromate in F344 rats the number of micronuclei in reticulocytes was significantly increased [10]. Finally, evidence of DNA damage has been observed in rats orally administered potassium bromate [11].

The weight of evidence demonstrates that bromate is clearly mutagenic in in vitro assays.
The positive findings in in vivo studies show that this mutagenicity is also expressed in vivo.


References

1.    Zeiger, E., et al., Salmonella mutagenicity tests: V. Results from the testing of 311 chemicals. Environmental & Molecular Mutagenesis, 1992. 19 Suppl 21: p. 2-141.
2.    Ishidate, M., Jr., et al., Primary mutagenicity screening of food additives currently used in Japan. Food & Chemical Toxicology, 1984. 22(8): p. 623-36.
3.    Speit, G., et al., Comparative evaluation of the genotoxic properties of potassium bromate and potassium superoxide in V79 Chinese hamster cells. Mutation Research, 1999. 439(2): p. 213-21.
4.    Priestley, C.C., et al., Anomalous genotoxic responses induced in mouse lymphoma L5178Y cells by potassium bromate. Toxicology, 2010. 267(1-3): p. 45-53.
5.    Fujie, K., et al., Acute cytogenetic effects of potassium bromate on rat bone marrow cells in vivo. Mutation Research, 1988. 206(4): p. 455-8.
6.    Hayashi, M., et al., Difference between intraperitoneal and oral gavage application in the micronucleus test. The 3rd collaborative study by CSGMT/JEMS.MMS. Collaborative Study Group for the Micronucleus Test/Mammalian Mutagenesis Study Group of the Environmental Mutagen Society of Japan. Mutation Research, 1989. 223(4): p. 329-44.
7.    Hayashi, M., et al., Micronucleus tests in mice on 39 food additives and eight miscellaneous chemicals. Food & Chemical Toxicology, 1988. 26(6): p. 487-500.
8.    Nakajima, M., et al., Effect of route of administration in the micronucleus test with potassium bromate. Mutation Research, 1989. 223(4): p. 399-402.
9.    Awogi, T., et al., Induction of micronucleated reticulocytes by potassium bromate and potassium chromate in CD-1 male mice. Mutation Research, 1992. 278(2-3): p. 181-5.
10.    Sai, K., et al., Effects of antioxidants on induction of micronuclei in rat peripheral blood reticulocytes by potassium bromate. Mutation Research, 1992. 269(1): p. 113-8.
11.    Kasai, H., et al., Oral administration of the renal carcinogen, potassium bromate, specifically produces 8-hydroxydeoxyguanosine in rat target organ DNA. Carcinogenesis, 1987. 8(12): p. 1959-61.





Short description of key information:
1) in vitro assays:
- Gene mutation in bacteria (Bacterial Reverse Mutation Assay/Ames): mutagenic in TA 1535, TA97, weakly mutagenic in TA100.
- CA in Chinese hamster fibroblast cells: mutagenic
- CA, MNT, DNA damage/repair and Comet assays in V79 Chinese hamster cells: mutagenic

2) in vivo assays
- MNT, HPRT, CA: positive

Endpoint Conclusion: Adverse effect observed (positive)

Justification for classification or non-classification

Provided key and supporting studies with potassium bromate did clearly show genotoxic potential in vitro and in vivo. This summary reveals some background information on the legal classification for carcinogenicity (see chapter 7.7). Further legal classification for germ cell mutagenicity is not rewarded.