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Bioassay of 1,2-dibromoethane for possible carcinogenicity
Abstract:
A bioassay for possible carcinogenicity of technical-grade 1,2-dibromoethane was conducted using Osborne-Mendel rats and B6C3F1 mice. 1,2-Dibromoethane in corn oil was administered by gavage, at either of two dosages, to groups of 50 male and 50 female animals of each species. The time-weighted average high and low doses of 1,2-dibromoethane used in the chronic bioassay were, respectively, 41 and 38 mg/kg/day for male rats, 39 and 37 mg/kg/day for female rats and 107 and 62 mg/kg/day for mice of both sexes. For each species 20 animals of each sex were placed on test as vehicle controls. These animals were gavaged with corn oil with the same frequency that dosed animals were gavaged with 1,2-dibromoethane mixtures. Twenty animals of each sex were placed on test as untreated controls for each species. These animals were not intubated. There was a positive association between increased dosage and accelerated mortality in rats and mice of both sexes. All surviving dosed male rats were sacrificed in week 49 and all surviving dosed female rats were sacrificed after 61 weeks of compound administration. All male mice and high dose female mice died or were sacrificed by week 78, while the low dose mice were observed for an additional 37 weeks after a 53-week period of chemical administration. In rats squamous-cell carcinomas of the forestomach were observed in 45/50, 33/50, 40/50 and 29/50 of the low dose males, high dose males, low dose females and high dose females, respectively, while none were observed in controls. Each of these incidences was statistically significant. These lesions were seen as early as week 12 in rats and week 24 in mice; they invaded locally and eventually metastasized. Increased incidences of hepatocellular carcinomas were observed in dosed rats, but the incidence of this neoplasm was significant only in females. Increased incidences of hemangiosarcomas were observed in each dosed rat group, but was statistically significant only in males, where they appeared as early as week 26. Early development of squamous-cell carcinomas which invaded and metastasized was also observed among mice. Squamous-cell carcinomas were found in 45/50, 29/49, 46/49 and 28/50 of the low dose males, high dose males, low dose females, and high dose females, respectively, but none were found in controls. Each of these incidences was statistically significant. Incidences of alveolar/bronchiolar adenomas were significant for male and female dosed mice. Under the conditions of this bioassay, 1,2-dibromoethane was carcinogenic to Osborne-Mendel rats and B6C3F1 mice. The compound induced squamous-cell carcinomas of the forestomach in rats of both sexes, hepatocellular carcinomas in female rats, and hemangiosarcomas in male rats. In mice of both sexes the compound induced squamous-cell carcinomas of the forestomach and alveolar/bronchiolar adenomas.
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