title: Carcinogenesis Bioassay of 1,2-Dibromo-3-chloropropane (CAS No. 96-12-8) in F344 Rats and B6C3F1 Mice (Inhalation Study).
abstract: 1,2-Dibromo-3-chloropropane (DBCP), a contaminant (0.05%) of the flame retardant tris(2,3-dibromopropyl)phosphate, has been used primarily as a soil fumigant to control nematodes. Unlike other halogenated nematocides, DBCP can be applied to soil without damaging growing perennials. Since it is slightly soluble in water at the concentrations used (30 ppm), DBCP can be either injected directly into the soil or added to irrigation water. By 1972, an estimated 12.3 million pounds were being used annually; in 1977, a total of 832,000 pounds were used in California, mostly on grapes and tomatoes. A carcinogenesis bioassay of technical grade 1,2-dibromo-3-chloropropane (DBCP), which contained trace amounts of epichlorohydrin and 1,2-dibromoethane, was conducted by exposing groups of 50 F344 rats and B6C3F1 mice of each sex by inhalation to concentrations of 0.6 or 3.0 ppm DBCP for 6 hours per day, 5 days per week, for 76 to 103 weeks. Untreated chamber controls consisted of 50 rats and 50 mice of each sex. Surviving high-dose rats were killed at week 84. Surviving high-dose female mice and low-and high-dose male mice were killed at week 76. Low-dose rats and female mice were killed at week 104. Accelerated mortality occurred in the high-dose groups of both species. Early deaths of high-dose rats and mice were associated with respiratory tract tumors. Interference with breathing and metastasis to the brain were major contributing factors in these deaths. Among male mice, accelerated mortality occurred in low-dose and control groups as well as in the high-dose group. Urogenital infection appeared to be associated with these deaths. Carcinomas, squamous-cell carcinomas, and adenocarcinomas of the nasal cavity and squamous-cell papillomas of the tongue each occurred in high-dose male rats at incidences significantly higher than those in the corresponding controls. Adenocarcinomas, adenomas, adenomatous polyps, and squamous-cell papillomas of the nasal cavity and adenomatous polyps of the nasal turbinates occurred in low-dose male rats with significantly increased incidences relative to controls. Carcinomas and adenocarcinomas of the nasal cavity, squamous-cell papillomas of the tongue, squamous-cell papillomas and carcinomas (combined) of the pharynx, and adenomas of the adrenal cortex each occurred in high-dose female rats at incidences significantly higher than those in the corresponding controls. Also, adenomas and squamous-cell papillomas of the nasal cavity, adenomas of the adrenal cortex, and fibroadenomas of the mammary gland were increased significantly in low-dose female rats when compared with controls. Adenocarcinomas of the nasal cavity in high-dose female mice, papillary carcinomas in low-dose female mice, and carcinomas, squamous cell carcinomas of the nasal cavity, and alveolar/bronchiolar adenomas or carcinomas of the lung in high-dose male and female mice occurred at incidences significantly higher than those in the corresponding controls. Exposure to DBCP vapor was also associated with toxic tubular nephropathy in rats and mice of either sex and with proliferative changes in the nasal mucosa, lung, and forestomach in mice. Under the conditions of this bioassay, DBCP was carcinogenic for male and female F344/N rats, including increased incidences of nasal cavity tumors and tumors of the tongue in both sexes, and cortical adenomas in the adrenal glands of females. DBCP was carcinogenic in male and female B6C3F1 mice, including increased incidences of nasal cavity tumors and lung tumors. Levels of Evidence of Carcinogenicity: Male Rats: Positive Female Rats: Positive Male Mice: Positive Female Mice: Positive Synonyms: DBCP; dibromochloropropane; Nemagon; Fumazone