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Environmental and Workplace Health

Bromate

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Classification and Assessment

No information is available on the induction of tumours by bromate in humans. Potassium bromate induced a dose-related increase in benign and malignant renal cell tumours in both sexes of F344 rats when administered in drinking water. Limited evidence of the induction of benign renal cell tumours was found in hamsters and in three strains of mice. Benign and malignant thyroid tumours and peritoneal mesotheliomas were also seen in male rats, and a significant increase in adenomas of the small intestine and liver was reported in mice. There is some evidence that bromate is detoxified by metabolism with GSH to bromide, although intermediate reactions with cell components also take place, releasing lipid peroxidases, which cause geno-toxic effects. Bromate gave largely negative results in bacterial mutagenicity tests, whereas positive results were obtained for clastogenic effects and DNA damage in all in vivo tests to date. Bromate has therefore been classified as probably carcinogenic to humans (sufficient evidence in animals; no data in humans).

Cancer risks have been estimated on the basis of renal cell tumours from two bioassays: one conducted in male and female F344 rats,39 and a second conducted at a lower range of doses in the same laboratory on males only.40,41 Given that these studies show that bromate is a non-threshold carcinogen, the model-free extrapolation method63 can be used. Using this method, one can calculate that the unit lifetime excess cancer risk associated with the ingestion of bromate at a concentration of 1 µg/L in drinking water ranges from 1.55 × 10-6 to 2.19 × 10-6 based on renal cell tumours in rats. The estimated range of bromate concentrations in drinking water corresponding to lifetime excess cancer risks of l0-4, 10-5 and 10-6 for renal cell tumours based on three data sets from studies by Kurokawa and colleagues is as follows:

Lifetime risk Concentration drinking water (µg/L)
10-4 46 - 65
10-5 4.6 - 6.5
10-6 0.46 - 0.65

There is some discussion as to whether bromate carcinogenesis is a result of a threshold effect. A study conducted in male F344 rats on the promoting effects of potassium bromate with and without initiation by EHEN44,45 appears to indicate a threshold level for promotion of renal tumorigenesis. This suggests that data obtained from studies of rats exposed at high doses may not be relevant to humans exposed at low doses; thus, the mathematical models for risk assessment may not be appropriate in this case. There is also concern about the relevance of the rat toxicity data to humans given that bromate may be genotoxic via an indirect mechanism (LPO) with a threshold, thus again suggesting that data obtained from studies of rats exposed at high doses are not relevant to humans exposed at low doses. However, bromate must be considered a non-threshold carcinogen until additional research provides sufficient evidence to prove otherwise.

It should be noted that peritoneal mesotheliomas that were observed39,40 may originate in rat-specific tissue (tunica vaginalis covering testis in male rats) and then spread to other tissues. As a result, this tumour would not be relevant to humans and as such was not used in determining lifetime excess cancer risk.

Although there was a third study49 from which the lifetime cancer risk could have been calculated, it was not available at the time the calculation was made. Given that the effect level for the study from which the risk was calculated was 1.7 mg/kg bw per day and that of the DeAngelo et al.49 study was 1.5 mg/kg bw per day, the risk is expected to be of the same order of magnitude.

Rationale

Because bromate has been classified as being probably carcinogenic to humans, the maximum acceptable concentration (MAC) is derived based on estimated lifetime cancer risk and available practicable treatment technology. As the MAC must also be measurable by available analytical methods, the PQL is also taken into consideration in its derivation.

An interim maximum acceptable concentration (IMAC) of 10 µg/L for bromate was established on the basis of the following considerations: (1) The IMAC must be measurable and achievable at reasonable cost. No treatment technology is available to remove bromate from drinking water; however, careful application of ozone treatment technology can minimize its formation in waters containing high bromide concentrations without compromising the level of disinfection.

(2) The PQL (based on the ability of laboratories to measure bromate within reasonable limits of precision and accuracy) for bromate in drinking water is 2 µg/L and well below the IMAC. It is based on the method reported by Lo and Subramanian,25 which has been successful in eliminating or minimizing interference by other DBPs. It is the recommended method for analysis of bromate in drinking water; however, it is a complex technique requiring experienced chromatographers. Currently, however, EPA Method 300.019 appears to be the most practical and widely available method, with a PQL of 10 µg/L.

(3) The MAC is designated as interim because the lifetime renal cancer risk associated with the ingestion of drinking water containing bromate at the IMAC is greater than the range that is considered generally to be essentially negligible. Based on the incidence of renal tumours in rats, the lifetime renal cancer risk associated with the ingestion of drinking water containing bromate at the IMAC of 10 µg/L is 2.19 × 10-4.

The IMAC will be reviewed periodically in light of developments in analytical and treatment technology and additional data on health risks associated with exposure to bromate in drinking water.


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References

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Date Modified: 2008-10-03

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