Inhalation toxicity of vinyl chloride and Vinylidene chloride

Abstract

Exposure of mice to 1000 ppm of vinyl chloride (VC), 6 hr/day, 5 days/week, caused some acute deaths with toxic hepatitis and marked tubular necrosis of the renal cortex. Starting the sixth month, mice exposed to 1000, 250, or 50 ppm of VC became lethargic, lost weight quickly, and died. Only a few mice exposed to 50 ppm survived for 12 months. Pulmonary macrophage count was elevated in some mice. There was a high incidence of bronchiolo-alveolar adenoma, mammary gland tumors including ductular adenocarcinoma, squamous and anaplastic cell carcinomas with metastasis to the lung, and hemangiosarcoma in the liver, and, to a lesser extent, in some other organs. The incidence of these tumors quickly increased, and the severity was in direct proportion to the levels of VC and the length of exposure. Malignant lymphoma involving various organs was observed in a few mice. Rats were more resistant to the toxic effects of VC. Exposure to 1000 ppm slightly depressed the body weight of the females. Exposures of 250 or 1000 ppm caused a number of deaths and hemangiosarcoma in the liver starting the ninth month. Most rats with hepatic hemangiosarcoma also developed hemangiosarcoma in the lung. Hemangiosarcoma occasionally occurred in other tissues of one or two rats exposed to 50 ppm or higher level of VC. Exposure of mice to 55 ppm of vinylidene chloride (VDC) also caused a few acute deaths and a few hepatic hemangiosarcomas. Inflammatory, degenerative, and mitotic changes occurred in the liver. No mouse exposed to VDC developed any mammary gland tumors. Several mice had bronchioloalveolar adenoma. Exposure of rats to 55 ppm of VDC slightly depressed the body weight. Hemangiosarcoma occurred in the mesenteric lymph node or subcutaneous tissue in two rats.

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

“…While in keeping with the observations made by other authors [4,7], the present results pro vide limited evidence of carcinogenicity of VDC in rodents. Additional evidence on which to base a final assessment of the carcinogenicity of VDC may be forth coming from studies known to be underway [15].…”

“…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.…”

Induction of Fibrosis and Autophagy in Kidney Cells by Vinyl Chloride

“…Survivors of AKI have up to a 28-fold are at higher risk for CKD than healthy individuals [29,30]. Previous studies showed that VC resulted in acute death with marked tubular necrosis of the renal cortex when mice were exposed to high doses of VC [31]. Other studies have shown that autophagy may attenuate fibrosis [32].…”

Review of pulmonary effects of poly(vinyl chloride) and vinyl chloride exposure.

“…The ultrastructure was thought to indicate that the tumors originated in type II alveolar cells. Alveologenic tumors were also described in several other experimental studies (25)(26)(27). Interestingly, other known carcinogens, such as polycyclic aromatic hydrocarbons, nitrogen mustard and chromates, produce pulmonary tumors in experimental animals similarly, originating in the type II alveolar cell.…”