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, 1,000, and 2,000 mg/L in the 2-week and 3-month studies, and 0, 50, 500, and 1,000 mg/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 50 mg/L, which is equivalent to an average daily dose of approximately 5 mg/kg. These studies provide critical information for future reevaluations of health-based drinking water standards for haloacetic acids.

Difficulty of mode of action determination for trichloroethylene: An example of complex interactions of metabolites and other chemical exposures

“…The results of Kato-Weinstein et al [2001], Tao et al [2004], Melnick et al [2007] are generally consistent for DBA and show a number of activities that may be common to TCE metabolites. Brominated and chlorinated haloacetate analogues generally have similar effects on liver glycogen accumulation, serum insulin levels, peroxisome Environmental and Molecular Mutagenesis.…”

“…Melnick et al [2007] reported the results of DBA exposure to F344/N rats and B6C3F 1 mice in a 3-month and 2-year drinking water bioassays. They reported neoplasms in multiple sites in both species exposed to DBA after 2 years.…”

“…Therefore, it is plausible that these effects may be additive in situations of coexposure. However, as discussed earlier, methylation status, events associated with PPARa agonism, hepatocellular necrosis, and regenerative hyperplasia are not established as key events in the MOA of these agents, and the MOAs for DCA-and DBA-induced liver tumors are unknown [Melnick et al, 2007].…”

Physiologically based pharmacokinetic modeling of dibromoacetic acid in F344 rats

“…Comparing these internal dose predictions with tumor incidence data from rodent assays (Carter et al, 2003; Melnick et al, 2007; NTP, 2007; NTP, 2009), would allow stronger conclusions about the dose-response for the carcinogenicity of these chemicals. Possible hypotheses that can be examined are: 1) inactivation of GSTzeta by DHA may increase the concentrations of DHAs in the liver thus contributing to the liver alterations induced by DHAs; 2) inactivation of GSTzeta by DHA may disrupt the tyrosine catabolism pathway resulting in toxicity endpoints (Ammini et al, 2003; Cornett et al, 1999; Lantum et al, 2002); and 3) increased GXA or OXA concentrations in the liver as a result of DHA metabolism might impact a liver tumor response.…”

Treatability of South African surface waters by activated carbon

“…It can be further classified as either particulate organic matter (POM) or dissolved organic matter (DOM). NOM in water affects the organoleptic aspects of the drinking water, promotes bacterial regrowth in drinking water distribution systems and reacts with disinfectants and oxidants, producing disinfection by-products and other products (Van der Kooij, 1998;Batterman et al, 2000;Hallam et al, 2001;Melnick et al, 2007;Edzwald and Tobiason, 2010;Ødegaard et al, 2010). NOM in raw water can be removed by different methods including the use of activated carbon.…”