Glutaraldehyde inhalation exposure of rats: Effects on lung morphology, Clara-cell protein, and hyaluronic acid levels in BAL

Glutaraldehyde (GA) is a biocide widely used in hospital and laboratory practice. GA is a volatile substance and, under certain circumstances, significant airborne concentrations may be generated at room temperature. Occupational exposure to GA by inhalation is suspected of causing delayed irritating effects. In recent years, GA has emerged as the main cause of occupational asthma among health-care workers. The aim of the present study was to evaluate effects of GA inhalatory exposure (0.025 ppm or 0.1 ppm, for 28 days) in rats exposed corresponding to the occupational shift cycle, at time point 24 h, 48 h, and 7 days postexposure (PE). Numerous vacuoles and dilated spaces in epithelial cells in bronchioles showing a destructive effect of GA on the cellular membrane were observed at 24 h PE in 0.1 ppm exposed rats. Lipid vacuoles observed after 48 h PE in higher GA exposure, in the Clara cells of the bronchial epithelium, and in endothelial cells of the alveolar capillaries are probably attributable to disturbed lipid metabolism. Many foci of collagen fibers were observed already after 7 days postexposure. Monitoring of inflammatory response and repair was made possible by using two biomarkers: Clara-cell protein (CC16) and hyaluronic acid (HA). Our results show that the inflammatory repair response contributed to progenitor Clara cells and HA plays a role in the development of fibrotic changes in the lung of rats. Glutaraldehyde in rats causes fibrotic effects at the actual threshold limit value-time weighted average (TLV-TWA) level for GA as specified by current Polish and other national regulations.