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

• Published in: Toxicology (Amsterdam) 2007-02, Vol.230 (2), p.126-136
• Main Authors: Melnick, Ronald L, Nyska, Abraham, Foster, Paul M, Roycroft, Joseph H, Kissling, Grace E
• Format: Article
• Language: English
• Subjects: Acetates - toxicity; Administration, Oral; Animals; Biological and medical sciences; Carcinogenicity Tests; Delayed spermiation; Dibromoacetic acid; Emergency; Epidemiology. Vaccinations; Female; Gastroenterology. Liver. Pancreas. Abdomen; General aspects; Hematologic and hematopoietic diseases; Hepatoblastoma; Hepatocellular adenoma/carcinoma; Histocytochemistry; Infectious diseases; Leukemia; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Liver Neoplasms - chemically induced; Liver Neoplasms - pathology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Lung Neoplasms - chemically induced; Lung Neoplasms - pathology; Male; Medical sciences; Mesothelioma; Mice; Mice, Inbred C57BL; Neoplasms, Experimental - chemically induced; Neoplasms, Experimental - pathology; Organ Size - drug effects; Other diseases. Semiology; Rats; Rats, Inbred F344; Testicular Neoplasms - chemically induced; Testicular Neoplasms - pathology; Toxicology; Water disinfection byproduct; Water Purification - methods
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2006.11.006

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 B6C3F1 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 2000 mg/L in the 2-week and 3-month studies, and 0, 50, 500, and 1000 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 4 mg/kg. These studies provide critical information for future re-evaluations of health-based drinking water standards for haloacetic acids.