Effect of methylene chloride inhalation on replicative DNA synthesis in the lungs of female B6C3F1 mice.

In the National Toxicology Program 2-year inhalation study of dichloromethane (DCM), there was a significant increase in pulmonary neoplasms in female B6C3F1 mice exposed to 2000 ppm (overall rates of 30/48 versus 5/50 in control). Replicative DNA synthesis was examined to evaluate the potential role of treatment-induced lung cell proliferation on pulmonary carcinogenicity. Tritiated thymidine incorporation was assessed in methacrylate plastic sections after 1, 2, 3, or 4 weeks of inhalation exposure to 2000 ppm or 8000 ppm DCM. Similar measurements of labeling indexes were made after 13 and 26 weeks of exposure to 2000 ppm DCM using bromodeoxyuridine as the labeling agent. In all cases the labeling agent was delivered over a 6-day period using osmotic minipumps. The labeling index (LI) of bronchiolar epithelium (two branches proximal to the terminal bronchiole) of mice exposed to 2000 ppm DCM for 2-26 weeks decreased to 40-60% of the control. Terminal bronchioles showed a similar decrease in LI. Mice exposed to 8000 ppm DCM had a less dramatic decrease in LI. No pathological change was found in the exposed lungs. It is concluded that inhalation exposure to DCM for up to 26 weeks reduces cell turnover of bronchiolar cells in female B6C3F1 mice.