Etiology of bromate-induced cancer and possible modes of action-studies in Japan
Section snippets
Carcinogenicity test in rats
Groups of 53 males and 53 females of F344 rats received KBrO3 for 110 weeks at concentrations of 500 (reduced to 400 ppm at week 60 in the males) and 250 ppm in the drinking water. Incidences of adenomas and adenocarcinomas and their combined incidences as renal cell tumors (RCTs) in the treated rats of both genders were significantly higher than the controls. Tumors of the peritoneum, all diagnosed as mesotheliomas, also occurred at a significantly higher incidence in male rats given 250 or 500
Limited duration study
Groups of 14–20 male F344 rats were given KBrO3 orally at concentration of 500 ppm for 13, 26, 39 or 52 weeks and maintained untreated up to the end of the experiment, week 104. The results revealed that 13 weeks of exposure was necessary to produce increase in the incidence of RCTs (Kurokawa et al., 1987). Further study confirming initiating potential of 13 weeks exposure to KBrO3 at various doses is now on-going based on a two-stage renal carcinogenesis model using trisodium nitrilotriacetate
Oxidative DNA damage
Five male and female rats in each group were administered KBrO3 at a concentration of 500 ppm in the drinking water for 1, 2, 3, 4 and 13 weeks, and then 8-hydroxydeoxyguanosine (8-OH-dG) levels in kidney nuclear DNA were measured using HPLC-ECD system. 8-OH-dG levels were increased at 1, 2, 3, 4 and 13 weeks in kidney DNA of male rats chronically exposed to KBrO3 at a carcinogenic dose, significant increase also being observed from 3 weeks up to the end of the experiment for females (Umemura et
Summary for the overall
The overall data were summarized in Fig. 1. Carcinogenicity studies demonstrated significantly elevated incidences of renal cell tumors in male and female rats given KBrO3 at 250 and 500 ppm in the drinking water. A further dose–response study using only male rats showed 125 ppm to also be a carcinogenic dose. However, since another group showed that a dose of 200 ppm failed to induce renal tumors in male rats (Wolf et al., 1998), it seems equivocal whether 125 ppm has a carcinogenic potential.
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