Chronic toxicity and oncogenicity study on inhaled vinylidene chloride in rats

Abstract

Male and female Sprague-Dawley rats (Spartan substrain) were exposed to vinylidene chloride (VDC) by inhalation for 18 months to assess chronic toxicity and oncogenic potential of the subject test material. Interim sacrifices were performed at 1, 6, and 12 months. Rats were exposed to VDC concentrations of 10 and 40 ppm for 6 hr/day, 5 days/week for the first 5 weeks of the study. Based upon the absence of observable treatment-related effects among rats sacrificed after 1 month of exposure, the exposure concentrations were increased to 25 and 75 ppm VDC. Exposures were continued at these concentrations through the 18th month of the study after which the surviving animals were held until 24 months and then sacrificed. Cytogenetic evaluations were performed on a separate group of animals, four rats/sex, exposed to 0,25, or 75 ppm VDC for 6 months. There were no exposure-related changes in the following parameters: mortality, appearance and demeanor, body weight data, clinical chemistry determinations, hematologic evaluations, urinalysis, or cytogenetic evaluation of bone marrow preparations. A target organ effect, characterized by hepatocellular fatty change in the midzonal region of the hepatic lobule which was minimal in severity, was observed in both male and female rats of both the 25- and 75-ppm exposure groups as early as the 6-month interim sacrifice. The midzonal fatty change was also observed at the 12-month sacrifice but no indication of progression of this lesion in either severity or incidence was apparent. During the last 6 months of the study, after exposures had been discontinued, this effect was no longer discernible; therefore this alteration was readily reversible. The incidences of several tumors and/or tumor types were statistically increased or decreased in VDC-exposed rats when compared to their respective control groups; none of these differences were judged to be attributable to VDC exposure.