Neoplastic effect of vinyl chloride in mouse lung--lower doses and short-term exposure.

Neoplastic pulmonary effects of lower doses of vinyl chloride (0 = control, 1, 10, 100, 300, and 600 ppm) and short-term exposure (4 weeks) by inhalation have been studied by light and electron microscopy in 220 mice. Except for dead or seriously sick animals, a large majority of the animals were sacrificed at three different stages: immediately after exposure, 12 weeks later, and 40 or 41 weeks after exposure. Six mice (4: 600 ppm, 2: 0 ppm) were kept longer than 41 weeks to examine the effects of the chemical after a long-term recovery period. Alveologenic tumors were first observed 10 weeks after exposure to 600 ppm. In the subgroups exposed to higher concentrations (600 and 300 ppm) the incidence of tumors was higher and their appearance was earlier than in the subgroups exposed to lower concentrations (100, 10, and 1 ppm). These findings indicated a dose-response relationship for incidence of alveologenic tumors, and the latency period was inversely related to dose. By light and electron microscopy, there was no obvious evidence that tumor cells were derived from Clara cells of the terminal bronchioles. Rather, neoplastic cells in both the tubulopapillary and adenomatous forms of the pulmonary tumors possessed all or some of the ultrastructural characteristics of type II alveolar cells, based on observations of mitochondria, microvilli, osmiophilic lamellar bodies, and other criteria. Type II alveolar cells are therefore considered to be the most sensitive in mice to the neoplastic effect of vinyl chloride.