Renal cell
tumors were significantly increased in male and female rats given
potassium bromate at 250 and 500 mg/L in
drinking water. In at least one other study renal cell
tumors were produced in male rats
at 125 mg/L. Among male mice given 750 mg/L of
potassium bromate, there were no significant differences in renal cell
tumors between treated and control groups after 88 weeks on test. In oxidative DNA damage tests 8-oxodeoxyguanosine (8-oxodG also referred to
as 8-
OH-dG) was induced in
DNA in the male rat kidney in 1 week, and in females after 3 weeks at 500 mg/L, and also in both male and female rats at 250 mg/L, but not
at 125 mg/L.
DNA adducts are considered to be an initial step in the
carcinogenesis process, however, the administered doses are not always sufficient to cause mutations, possibly due to DNA repair. In the two-step rat renal
carcinogenesis model using
N-ethyl-N-hydroxyethylnitrosamine (EHEN) as initiator, promotion activity by
potassium bromate was measured using the
BrdU labeling index. The promoting activity of
bromate in male rats was much greater and extended to doses as low as 60 mg/L in male rats, whereas in females the response was limited to 250 and 500 mg/L. Therefore, it was concluded that the mechanisms contributing to
cancer in the male rat were more complex than in the female rat. The accumulation of
alpha2mu-globulin in the kidneys of male rats exposed to
potassium bromate probably accounts for the greater labeling index in the male rat relative to the female rat. Accumulation of
alpha(2mu)-globulin as a result of treatment with chemicals is unique to the male rat and does contribute to carcinogenic responses. Neither humans nor female rats display this response. Nevertheless,
bromate must be considered carcinogenic because of the response of the female rats. The better correlation between
8-oxodG formation and
tumor response indicates that dose-response information from the female rat would be much more relevant to human risk assessment. The fact that an elevation of
BrdU-LI in the kidney of the female rat is consistent with the possibility that cell proliferation observed in female rats resulted from oxidative stress and/or cytotoxic responses in the kidney. Therefore, oxidative stress is most likely the mechanism of interest for
cancer risk in humans.