A series of long-term inhalation studies of diesel exhaust and intratracheal instillation of diesel particles was conducted on female SPF F344 rats. A particulate but not gaseous component in the inhalation studies provoked inflammatory changes and tumors in the lung, and the intratracheally instilled particles showed similar findings. Adenoma and adenocarcinoma were the main histologic types of the tumors which developed and they showed the phenotype of surfactant apoprotein-producing cells, suggesting that the tumor cell origin was a Type II alveolar cell. The tumor incidence rate correlated with the cumulative concentration of inhaled particles per week and with the amount of particles deposited in the lung. In the instillation studies, the carbon core of diesel particles obtained after exhaustive extraction of tarry matter showed a slightly lower positive rate of lung tumor formation than the rate in untreated diesel particles, indicating an important role of carbon core in the diesel particle-induced tumor. In the intratracheal instillation studies, point mutation of K-ras oncogene was detected in a significant percentage in the tumor cells.
