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Published on: May 4, 2016
Time- and dose-dependent development of potassium bromate-induced tumors in male Fischer 344 rats
D C Wolf1, L M Crosby, M H George
1Environmental Carcinogenesis Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. wolf.doug@epamail.epa.gov
Abstract:
Potassium bromate (KBrO3) is a rodent carcinogen and a nephro- and neurotoxicant in humans. KBrO3 is used in cosmetics and food products and is a by-product of water disinfection by ozonization. KBrO3 is carcinogenic in the rat kidney, thyroid, and mesothelium and is a renal carcinogen in the male mouse. The present study was designed to investigate the relationship of time and dose to bromate-induced tumors in male Fischer 344 (F344) rats and to provide some insight into the development of these tumors. KBrO3 was dissolved in drinking water at nominal concentrations of 0, 0.02, 0.1, 0.2, and 0.4 g/L and administered to male F344 rats as the sole water source for 12, 26, 52, 78, or 100 wk. Renal cell tumors were present after 52 wk of treatment only in the high-dose group. Mesotheliomas developed after 52 wk of treatment on the tunica vaginalis. Mesotheliomas were present at sites other than the testicle after 78 wk of treatment, indicating that their origin was the testicular tunic. Thyroid follicular tumors were present as early as 26 wk in 1 rat each from the 0.1- and 0.2-g/L groups. The present study can be used as a basis for the determination of dose-time relationships of tumor development for a better understanding of KBrO3-induced cancer.
Insights
Potassium bromate (KBrO3) exposure causes tumors in rats, including kidney and thyroid cancers. Higher doses and longer exposure times increased tumor development, highlighting dose-time relationships in KBrO3 carcinogenicity.
Area of Science:
- Toxicology
- Carcinogenesis
- Environmental Health
Background:
- Potassium bromate (KBrO3) is a known rodent carcinogen and a human nephro- and neurotoxicant.
- KBrO3 finds use in cosmetics and food products and is generated during water ozonization.
- Previous studies indicate KBrO3 carcinogenicity in rat kidney, thyroid, and mesothelium, and renal carcinogenicity in male mice.
Purpose of the Study:
- To investigate the dose-time relationship of potassium bromate-induced tumor development in male Fischer 344 rats.
- To gain insight into the mechanisms underlying KBrO3-induced tumorigenesis.
Main Methods:
- Male Fischer 344 rats were administered drinking water containing potassium bromate (KBrO3) at concentrations of 0, 0.02, 0.1, 0.2, and 0.4 g/L.
- Exposure durations varied, including 12, 26, 52, 78, and 100 weeks.
- KBrO3 was the sole source of water for the experimental animals.
Main Results:
- Renal cell tumors were observed in the high-dose group after 52 weeks of treatment.
- Mesotheliomas developed on the tunica vaginalis after 52 weeks and at other sites by 78 weeks, originating from the testicular tunic.
- Thyroid follicular tumors appeared as early as 26 weeks in rats from the 0.1- and 0.2-g/L groups.
Conclusions:
- Tumor incidence and development are dependent on both the dose and duration of potassium bromate exposure.
- The study provides a basis for understanding dose-time relationships in KBrO3-induced carcinogenesis.
- Findings underscore the carcinogenic potential of KBrO3 and the need for monitoring its presence in consumer products and the environment.
