Bioassay of dibromochloropropane for possible carcinogenicity.
A bioassay for possible carcinogenicity of technical-grade dibromochloropropane (DBCP) was conducted using Osborne-Mendel rats and B6C3F1 mice. DBCP in corn oil was administered by gavage 5 days a week, at either of two dosages, to groups of 50 male and 50 female animals of each species. Initial dosage levels for the chronic bioassay were selected on the basis of a preliminary subchronic toxicity test. Subsequent dosage adjustments were made during the course of the chronic bioassay. The time-weighted average dosages of DBCP in the chronic study were 29 mg/kg/day for the high dose rats of both sexes, and 15 mg/kg/day for the low dose rats of both sexes. The time-weighted average concentrations for the high dose male and female mice were 219 and 209 mg/kg/day, respectively. The time-weighted average concentrations for the low dose male and female mice were 114 and 110 mg/kg day, respectively. For each species, 20 animals of each sex were placed on test as vehicle controls. These animals were intubated with corn oil at the same time that dosed animals were intubated with DBCP mixtures. Twenty animals of each sex were placed on test as untreated controls for each species. These animals received no gavage treatments. DBCP was administered to the high dose male and high dose female rats for 64 weeks prior to sacrifice, and to the low dose female rats for 73 weeks prior to sacrifice. The low dose male rats were treated for 78 weeks followed by an additional 5 weeks of observation. The high dose male and female mice were treated for 47 weeks prior to sacrifice; the low dose male mice were treated for 59 or 60 weeks prior to sacrifice, and the low dose female mice were treated for 60 weeks prior to sacrifice. In rats and mice of both sexes, statistically significant incidences of squamous-cell carcinomas of the forestomach occurred in each dosed group and a significant positive association existed between dosage level and tumor incidence. The incidences of adenocarcinomas of the mammary gland were statistically significant in female rats when the treated groups were compared to the controls. Toxic nephropathy was also observed at elevated incidences in all of the treated rats and mice when compared to their respective untreated or vehicle control groups. Under the conditions of this study, DBCP is a stomach carcinogen in rats and mice of both sexes and is carcinogenic to the mammary gland in female rats.