Carcinogenesis Bioassay of 1,2-Dibromoethane (CAS No. 106-93-4) in F344 Rats and B6C3F1 Mice (Inhalation Study).
A carcinogenesis bioassay of 1,2-dibromoethane, a widely used nematocide and leaded gasoline additive, was conducted by exposing groups of 50 F344 rats and B6C3F1 mice of each sex by inhalation to concentrations of 10 or 40 ppm of the 1,2-dibromoethane for 78-103 weeks. Untreated controls consisted of 50 rats and 50 mice of each sex exposed in chambers to ambient air. Throughout the study, mean body weights of high-dose rats and high-dose mice of either sex were lower than those of the corresponding untreated controls. Survival of the high-dose rats of either sex and of the low- and high-dose female mice was significantly shorter than that in the corresponding controls. The principal cause of early death in control and dosed male mice was ascending, suppurative urinary tract infection that resulted in necrotic, ulcerative lesions around the urethral opening, chronic or suppurative cystitis (often with urinary tract obstruction), and ascending suppurative pyelonephritis. Carcinomas and adenocarcinomas of the nasal cavity were observed with significantly increased incidences (P<0.001) in high-dose rats of either sex relative to controls. The incidences of adenocarcinomas and adenomas of the nasal cavity were also significantly increased (P<0.001) in low-dose rats of either sex. Adenomatous polyps of the nasal cavity showed significantly increased incidence (P<0.001) in low-dose male rats. The combined incidence of alveolar/bronchiolar adenomas and carcinomas was statistically significant (P=0.024) for high-dose female rats. Hemangiosarcomas of the circulatory system (mainly spleen) and mesotheliomas of the tunica vaginalis occurred in high-dose male rats with significantly increased incidences (P<0.001) relative to controls. The incidence of fibroadenomas of the mammary gland was significantly elevated (P<0.001) in dosed female rats relative to controls. The incidences of alveolar/bronchiolar carcinoma and alveolar/bronchiolar adenoma were significantly increased(P<0.001) in high-dose male mice relative to controls. These tumors were also increased in high-dose female mice (P=0.007 for adenomas and P<0.001 for carcinomas). Hemangiosarcomas occurred in low- and high dose female mice at incidences significantly greater (P<0.001) than the incidence in the controls (0/50). High-dose female mice also had significantly increased incidences of subcutaneous fibrosarcomas (P<0.001) and of nasal cavity carcinomas (P=0.013). Low-dose female mice also showed a significantly increased incidence (P<0.001) of mammary gland adenocarcinomas. Exposure to 1,2-dibromoethane was also associated with hepatic necrosis and toxic nephropathy in rats of either sex, testicular degeneration in male rats, retinal degeneration in female rats, and epithelial hyperplasia of the respiratory system in mice. Under the conditions of this bioassay, 1,2-dibromoethane was carcinogenic for F344 rats, causing increased incidences of carcinomas, adenocarcinomas, adenomas of the nasal cavity, and hemangiosarcomas of the circulatory system in males and females; mesotheliomas of the tunica vaginalis and adenomatous polyps of the nasal cavity in males; and fibroadenomas of the mammary gland and alveolar/bronchiolar adenomas and carcinomas (combined) in females. 1,2-Dibromoethane was carcinogenic for B6C3F1 mice, causing alveolar/bronchiolar carcinomas and alveolar/bronchiolar adenomas in males and females; and hemangiosarcomas of the circulatory system, fibrosarcomas in the subcutaneous tissue, carcinomas of the nasal cavity, and adenocarcinomas of the mammary gland in females. Levels of Evidence of Carcinogenicity: Male Rats: Positive Female Rats: Positive Male Mice: Positive Female Mice: Positive Synonyms: ethylene dibromide; EDB; ethylene bromide