rodents and among rodents and humans in number and structure (ReznikSchuler 1976; Buckpitt et al. 1995). In mice, Clara cells are numerous and are spread throughout the airways, whereas in rats they are significantly fewer, particularly in the terminal bronchiolar region. In human lung, Clara cells are rare, as they are found in small numbers in the distal bronchioles. Mouse lung Clara cells are packed with endoplasmic reticulum, but human Clara cells are devoid of these membranes (Reznik-Schuler 1976; Buckpitt et al. 1995). The membranes of the endoplasmic reticulum in the Clara cell are the site of origin of the trichloroethylene-induced lesion in the mouse, consistent with the location of high concentrations of cytochrome P-450 enzymes that metabolize trichloroethylene in those membranes.
In summary, the metabolic data suggest that humans will be much less sensitive than mice to trichloroethylene-induced Clara cell toxicity and lung tumor development. One would not expect humans to develop lung tumors after exposure to ambient levels of trichloroethylene, which is in agreement with the results of epidemiology studies that show no association between trichloroethylene exposures and an increased in incidence of lung tumors.
Trichloroethylene has been shown to induce lung tumors in rodents. It is well documented that the mode of action for this effect is localization of the metabolite chloral in Clara cells of the lungs and that pulmonary metabolism of trichloroethylene to chloral is species dependent. The weight of evidence indicates that rodents and humans differ significantly in their capacity to metabolize trichloroethylene in their lungs, with humans having less capacity to metabolize the compound. This is supported by the results of most epidemiologic studies of occupational exposure to trichloroethylene, which do not show a strong association between trichloroethylene exposure and an increased incidence of lung tumors. Thus, pulmonary cancer is does not appear to be a critical end point in assessing human health risks of trichloroethylene.