Abstract for TR-228

A subchronic and a chronic carcinogenesis study of vinylidene chloride (99% pure), a widely used chemical intermediate and monomer, were conducted in F344/N rats and B6C3F1/N mice. In subchronic studies, groups of 10 rats and 10 mice of either sex were administered vinylidene chloride in corn oil by gavage five times per week at 0, 5, 15, 50, 100, or 250 mg/kg body weight for 13 weeks. At the end of this study, representative tissues from these animals were subjected to histopathological examination. The liver was identified as a target organ for vinylidene chloride toxicity.

In the 104-week chronic exposure study, conducted primarily to determine possible carcinogenic potential of vinylidene chloride by the oral route, 50 F344/N rats and 50 B6C3F1/N mice of either sex were gavaged with vinylidene chloride suspended in corn oil at dose levels of 1 or 5 mg/kg (rats) and 2 or 10 mg/kg (mice). Groups of 50 rats and 50 mice of either sex received corn oil alone and served as vehicle controls.

Throughout most of the study, mean body weights of the dosed rats of either sex and high-dose female mice were slightly lower than those of the controls. The absence of compound-related effects on survival or clinical signs suggests that the rats and mice of either sex could have tolerated higher doses. While no significant differences in survival were observed for any group of rats, 12 control and 10 low-dose males were killed accidentally during week 82; this may have compromised the sensitivity of the male rats study.

The results of histopathological examination indicated an increased incidence of necrosis of the liver in high-dose male and low-dose female mice and chronic renal inflammation in high-dose rats of either sex.

The only observed significant (P>0.05) increase in tumor incidence occurred in low-dose female mice: lymphoma (2/48, 9/49, 6/50) and lymphoma or leukemia (7/48, 15/49, 7/50). These increases were not considered to be related to vinylidene chloride administration because similar effects were not found in the high-dose female mice or in male mice or rats.

Under the conditions of this bioassay, vinylidene chloride administered by gavage was not carcinogenic for F344/N rats or B6C3F1/N mice of either sex. However, since the use of a maximum tolerated dose in this study has not been clearly demonstrated and since previously reported studies have shown that carcinogenicity is associated with inhalation exposure to vinylidene chloride, this study should not be taken as proof that the chemical is not a carcinogen.