Toxicity and carcinogenicity of the water disinfection byproduct, dibromoacetic acid, in rats and mice

Abstract

Dibromoacetic acid (DBA) is a water disinfection byproduct formed by the reaction of chlorine oxidizing compounds with natural organic matter in water containing bromide. Male and female F344/N rats and B6C3F(1) mice were exposed to DBA in drinking water for 2 weeks (N=5), 3 months (N=10), or 2 years (N=50). Concentrations of DBA in drinking water were 0, 125, 250, 500, 1000, and 2000mg/L in the 2-week and 3-month studies, and 0, 50, 500, and 1000mg/L in the 2-year studies. Toxic effects of DBA in the prechronic studies were detected in the liver (hepatocellular cytoplasmic vacuolization in rats and mice) and testes (delayed spermiation and atypical residual bodies in male rats and mice, and atrophy of the germinal epithelium in rats). In the 2-year studies, neoplasms were induced at multiple sites in rats and mice exposed to DBA; these included mononuclear cell leukemia and abdominal cavity mesothliomas in rats, and neoplasms of the liver (hepatocellular adenoma or carcinoma and hepatoblastoma) and lung (alveolar adenoma or carcinoma) in mice. The increase in incidence of hepatocellular neoplasms in male mice was significant even at the lowest exposure concentration of 50mg/L, which is equivalent to an average daily dose of approximately 4mg/kg. These studies provide critical information for future re-evaluations of health-based drinking water standards for haloacetic acids.

Figure 1

Marked (grade 4) seminiferous atrophy (end stage lesion) in the testis of a rat treated with 2000 mg/L of DBA for 13 weeks. All tubules (arrows) in the field are atrophic.

Figure 2

Presence of numerous abnormal residual bodies (arrows) in the testis of a rat treated with 1000 mg/L of DBA for 13 weeks.

Figure 3

Presence of numerous abnormal residual bodies (arrows) in the testis of a mouse treated with 2000 mg/L of DBA for 13 weeks.

Figure 4

Malignant mesothelioma (arrow) growing on the serosal surface of the testis in a male rat treated with 1000 mg/L of DBA for 2 years. A spontaneous interstitial cell tumor is also present.