Toxicity and carcinogenicity of potassium bromate--a new renal carcinogen.
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.
Kurokawa
Y
Y
Division of Toxicology, National Institute of Hygienic Sciences, Tokyo, Japan.
Maekawa
A
A
Takahashi
M
M
Hayashi
Y
Y
D000230:Adenocarcinoma / Q000139:chemically induced; D000284:Administration, Oral; D000818:Animals; D001939:Bread / Q000032:analysis; D001959:Bromates / Q000009:adverse effects / Q000493:pharmacokinetics / Q000506:poisoning / Q000633:toxicity*; D001965:Bromides / Q000032:analysis / Q000633:toxicity; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000493:pharmacokinetics / Q000633:toxicity*; D002292:Carcinoma, Renal Cell / Q000139:chemically induced*; D002869:Chromosome Aberrations; D003043:Cocarcinogenesis; D006224:Cricetinae; D003545:Cysteine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005396:Fish Products; D005503:Food Additives / Q000009:adverse effects / Q000633:toxicity*; D005511:Food Handling; D005978:Glutathione / Q000378:metabolism; D006203:Hair Preparations / Q000506:poisoning*; D034381:Hearing Loss / Q000139:chemically induced; D006801:Humans; D007564:Japan / Q000453:epidemiology; D007674:Kidney Diseases / Q000139:chemically induced; D007680:Kidney Neoplasms / Q000139:chemically induced*; D008452:Maximum Allowable Concentration; D008647:Mesocricetus; D008654:Mesothelioma / Q000139:chemically induced; D051379:Mice; D009152:Mutagenicity Tests; D009784:Occupational Diseases / Q000139:chemically induced / Q000453:epidemiology; D010534:Peritoneal Neoplasms / Q000139:chemically induced; D011188:Potassium / Q000032:analysis / Q000633:toxicity; D017680:Potassium Compounds; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D013964:Thyroid Neoplasms / Q000139:chemically induced; D006113:United Kingdom; D014481:United States / Q000453:epidemiology
D001959:Bromates; D001965:Bromides; D002273:Carcinogens; D005503:Food Additives; D006203:Hair Preparations; D017680:Potassium Compounds; C019536:potassium bromate; D005978:Glutathione; D003545:Cysteine; C039004:potassium bromide; D011188:Potassium