Dose-response studies on the carcinogenicity of potassium bromate in F344 rats after long-term oral administration.
Dose-response studies on the carcinogenicity of potassium bromate (KBrO3), a food additive, were undertaken to examine its effects at low doses. A total of 148 6-week-old male inbred F344 rats were divided into 7 groups. They were given KBrO3 orally in their drinking water at doses of 500, 250, 125, 60, 30, 15, and 0 ppm for 104 weeks, at the end of which time all the surviving animals were autopsied and then examined histopathologically. Shortening of the survival times and marked inhibition of body weight increase were observed in a group given 500 ppm KBrO3. The combined incidences of renal adenocarcinomas and adenomas were significantly increased in rats treated with KBrO3 at doses of 500, 250, and 125 ppm in a dose-related manner. The dose-response curve showed a sigmoid appearance. The value for the virtually safe dose (VSD), calculated by the probit model, was 0.950 ppm KBrO3 at a risk level of 10(-6). However, significant increases in the occurrence of dysplastic foci of the kidney were found in groups at doses higher than 30 ppm KBrO3. The VSD value for the dysplastic foci estimated by the gamma-multi-hit model was 0.148 X 10(-3) ppm KBrO3 at a risk level of 10(-6). In a group tested with 500 ppm KBrO3, the combined incidences for follicular adenocarcinomas and adenomas of the thyroid and for mesotheliomas of the peritoneum were shown to be significantly increased.
Kurokawa
Y
Y
Aoki
S
S
Matsushima
Y
Y
Takamura
N
N
Imazawa
T
T
Hayashi
Y
Y
D000230:Adenocarcinoma / Q000139:chemically induced; D000236:Adenoma / Q000139:chemically induced; D000818:Animals; D001959:Bromates / Q000008:administration & dosage / Q000633:toxicity*; D001966:Bromine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005503:Food Additives / Q000633:toxicity; D007680:Kidney Neoplasms / Q000139:chemically induced; D008297:Male; D008654:Mesothelioma / Q000139:chemically induced; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D010534:Peritoneal Neoplasms / Q000139:chemically induced; D051381:Rats; D011916:Rats, Inbred F344; D013964:Thyroid Neoplasms / Q000139:chemically induced
D001959:Bromates; D005503:Food Additives; C019536:potassium bromate; D001966:Bromine