Consequences of prolonged inhalation of ozone on F344/N rats: collaborative studies. Part XII: Atrophy of bone in nasal turbinates

Abstract

As part of the National Toxicology Program/Health Effects Institute collaborative study of the health effects of prolonged ozone exposure, it was observed that rats chronically exposed to ozone had marked histopathologic changes in the upper respiratory tract, including atrophy of the nasal turbinates. The principal objective of the present study was to morphometrically assess the severity of the ozone-induced changes in the bony tissue of the maxilloturbinates in these chronically exposed rats. Male and female F344/N rats were exposed to 0, 0.12, 0.5, or 1.0 part per million (ppm) ozone, 6 hours/day, 5 days/week for 20 or 24 months. Rats were killed one week after the end of the exposure, and nasal tissues were processed for light and electron microscopy. Using image analysis and standard morphometric techniques, the amounts of bone, surface epithelium, and lamina propria comprising the maxilloturbinates were estimated by measuring the cross-sectional area of each tissue compartment at a defined location in the proximal nasal passage. Both male and female rats had significant morphologic and morphometric changes in the maxilloturbinates after prolonged exposures to 0.5 or 1.0 ppm ozone, but not to 0.12 ppm ozone. Ozone-exposed rats had significant reductions in the cross-sectional area of turbinate bone, reflecting the loss of bone in the maxilloturbinate after prolonged exposure. This ozone-induced bony atrophy was more severe in male than in female rats. Using electron microscopy, numerous bone-resorption sites were identified on the outer, periosteal, surface of the turbinate bone in ozone-exposed animals. Rats with bony atrophy also had a conspicuous influx and mixed inflammatory cells into the lamina propria surrounding the turbinate bone. In addition, ozone exposures caused reductions in the area of lamina propria, due to blood vessel constriction, and increases the in the area of the surface epithelium, due to hyperplasia and metaplasia. The results of the present tudy demonstrated that prolonged exposure of rats to ozone can cause marked loss of turbinate bone. The severity of this ozone-induced bony atrophy in rats is dependent on both concentration and gender.