Interim results of two-year toxicological studies in rats of vinylidene chloride incorporated in the drinking water or administered by repeated inhalation

Abstract

Male and female Sprague-Dawley rats were exposed to vinylidene chloride (VDC) orally or by inhalation in 2-year toxicological studies. Interim results are included in this report. VDC was given in the drinking water at mean ± S.D. concentrations of 0, 68 ± 13, 106 ± 22, and 220 ± 35 ppm which produced mean ± S.D. dosage levels of 0, 5.9 ± 0.6, 10.0 ± 1.2, and 19.3 ± 2.7 mg/kg for male rats and 0, 7.5 ± 0.4, 12.6 ± 1.1, and 25.6 ± 2.4 mg/kg for female rats. Forty-eight rats/sex/VDC level and 80 rats/sex in the control group were used in the 2-year study with an interim kill of an additional 10 rats/sex/level at 90 days. In the inhalation study, rats were exposed to 0, 10, or 40 ppm of VDC vapor 6 hr/day, 5 days/week for 5 weeks, after which the exposure levels were changed to 0, 25, and 75 ppm of VDC. Exposure continued for a total of 18 months and the rats held for observation an additional 6 months. Interim kills occurred at 1, 6 and 12 months. A separate 90-day study using 20 rats/sex/level was conducted at 0, 25, and 75 ppm of VDC vapor. There were 86 rats/sex/level in the 2-year portion of the study. The parameters monitored were: body weight, food and water consumption (drinking water study only), hematology, clinical chemistries, cytogentics of bone marrow cells (inhalation study only), mortality, terminal organ weights, and gross and histopathology. Based on interim kills and gross pathologic observations, the main conclusions are: increased cytoplasmic vacuolation of hepatocytes was seen in the livers of rats given 200 ppm VDC in drinking water or 25 or 75 ppm VDC vapor by inhalation; based on gross tumor count, tumor incidence in VDC-exposed rats was not greater than controls.

Assessment of the mode of action of perchloroethylene-induced mouse liver tumors

“…The rat liver was refractory to the tumorigenic effects of PCE. In addition to the studies above, additional carcinogenicity studies by Rampy et al (Rampy et al, 1978) and Maltoni and Cotti (Maltoni and Cotti, 1986) have shown a lack of a tumor response in the rat following chronic exposure to PCE (see Table 3). The negative liver tumor response in the rat is valuable in examining possible mechanisms for PCE-induced mouse liver tumors.…”

“…In chronic studies examining the carcinogenicity of TCA or PCE in the liver, the rat, unlike the mouse, did not show an increase in liver neoplasms (NTP, 1986; JISA, 1993; NCI, 1977; Rampy et al, 1978; Maltoni and Cotti, 1986; DeAngelo et al, 1997) (Table 7). To further define this species difference in tumor induction several studies examined the induction of the PPARα-related PCO activity in the rat after treatment with TCA (Table 7).…”

Long-Term Testing of Vinylidene Chloride and Chloroprene for Carcinogenicity in Rats

“…The results of a number of long term carcinogenicity tests have recently become avail able, either as preliminary communications or as interim results of on-going studies [4][5][6], The preliminary re sults of one study, in which VDC was given by inhala tion, point to the induction of kidney carcinoma in mice and to an increased incidence of mammary tumours in rats, no carcinogenic effect was observed when VDC was administered by the oral route to rats or hamsters [4], An increased incidence of lung, skin and liver cell tumours in mice and the induction of haemangiosarcomas in both mice and rats was reported in another inhalation study [7], In addition, VDC has been shown to be mutagenic to Salmonella typhimurium [8], Chloroprene (CP) is used as a chemical intermediate, mainly as the monomer in the manufacture of synthetic elastomers. World production of this compound in 1977 is estimated to have been 300,000 t.…”