potassium-bromate and Adenocarcinoma

Potassium bromate (KBrO3) is an oxidizing agent that has been used as a food additive, mainly in the bread-making process. Although adverse effects are not evident in animals fed bread-based diets made from flour treated with KBrO3, the agent is carcinogenic in rats and nephrotoxic in both man and experimental animals when given orally. It has been demonstrated that KBrO3 induces renal cell tumors, mesotheliomas of the peritoneum, and follicular cell tumors of the thyroid. In addition, experiments aimed at elucidating the mode of carcinogenic action have revealed that KBrO3 is a complete carcinogen, possessing both initiating and promoting activities for rat renal tumorigenesis. However, the potential seems to be weak in mice and hamsters. In contrast to its weak mutagenic activity in microbial assays, KBrO3 showed relatively strong potential inducing chromosome aberrations both in vitro and in vivo. Glutathione and cysteine degrade KBrO3 in vitro; in turn, the KBrO3 has inhibitory effects on inducing lipid peroxidation in the rat kidney. Active oxygen radicals generated from KBrO3 were implicated in its toxic and carcinogenic effects, especially because KBrO3 produced 8-hydroxydeoxyguanosine in the rat kidney. A wide range of data from applications of various analytical methods are now available for risk assessment purposes.

Topics: Adenocarcinoma; Administration, Oral; Animals; Bread; Bromates; Bromides; Carcinogenicity Tests; Carcinogens; Carcinoma, Renal Cell; Chromosome Aberrations; Cocarcinogenesis; Cricetinae; Cysteine; Dose-Response Relationship, Drug; Fish Products; Food Additives; Food Handling; Glutathione; Hair Preparations; Hearing Loss; Humans; Japan; Kidney Diseases; Kidney Neoplasms; Maximum Allowable Concentration; Mesocricetus; Mesothelioma; Mice; Mutagenicity Tests; Occupational Diseases; Peritoneal Neoplasms; Potassium; Potassium Compounds; Rats; Rats, Inbred F344; Species Specificity; Thyroid Neoplasms; United Kingdom; United States

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.

Topics: Adenocarcinoma; Adenoma; Animals; Bromates; Bromine; Dose-Response Relationship, Drug; Food Additives; Kidney Neoplasms; Male; Mesothelioma; Neoplasms, Experimental; Peritoneal Neoplasms; Rats; Rats, Inbred F344; Thyroid Neoplasms

The carcinogenicity of potassium bromate, a food additive and a neutralizer in permanent waving, was tested by adding it to the drinking water of F344 rats for 110 weeks. Groups of 53 males and 53 females, each, were given solutions of 500 or 250 ppm of potassium bromate or distilled water. A concentration of 500 ppm markedly inhibited an increase of body weight of male rats. The mean survival time was shortest for males given 500 ppm (88.1 +/- 18.1 wk); the survival times of other groups were 101-104 weeks. The percentage survival in week 104 was relatively high in all groups, and it was 77.4% for males and 66.0% for females in the control group. High incidences of renal cell tumors (in males and females given 500 or 250 ppm) and mesotheliomas of the peritoneum (in males given 500 ppm) were observed. The incidences of these tumors in test groups were significantly higher than those in controls (P less than .001). It was concluded that, when orally administered under the conditions of this experiment, potassium bromate was carcinogenic to F344 rats.

Topics: Adenocarcinoma; Adenoma; Animals; Body Weight; Bromates; Bromine; Female; Food Additives; Hair Preparations; Kidney Neoplasms; Male; Mesothelioma; Peritoneal Neoplasms; Probability; Rats; Rats, Inbred F344

Topics: Adenocarcinoma; Administration, Oral; Animals; Bromates; Bromine; Female; Food Additives; Kidney Neoplasms; Male; Neoplasms, Experimental; Rats; Rats, Inbred F344

Topics: Adenocarcinoma; Administration, Oral; Animals; Bromates; Bromine; Female; Food Additives; Hair Preparations; Kidney Neoplasms; Male; Neoplasms, Experimental; Rats