Nononcogenic pulmonary diseases are the third leading cause of death in the US and are a major factor in morbidity and disability.
Pulmonary cancer is the leading cause of cancer-related deaths.
Although cigarette smoking is a major etiologic factor in these diseases, exposure to chemicals in the workplace and in the environment may be important as well. Numerous studies in laboratory animals have demonstrated the importance of the lung as a target for both inhaled and ingested chemicals. Because the studies in rodents have shown high variability in species and regional sensitivity within the lung to these chemicals, the applicability of studies in rodents for estimating the risks of exposure to humans is questionable. There is no understanding of how the factors thought to be critical for determining lung toxicity in rodents applies to the anatomically, cellularly, and metabolically distinct human lung. These studies test the postulate that some rodent lung toxicants metabolically activated by P450 also produce focal injury in human lung.