Respiratory tract lesions induced by sensory irritants at the RD50 concentration

Exposure of mice to airborne sensory irritants causes a concentration-dependent depression of respiratory rate. The RD50 concentration (that concentration which elicits a respiratory rate decrease of 50%) has been predicted to be an unacceptable occupational exposure concentration due to intolerable sensory irritation and possible respiratory tract injury in humans. The purpose of this study was (1) to determine whether lesions occur in the respiratory tract of Swiss-Webster mice after exposure to the RD50 concentrations of ten sensory irritants and (2) to compare these changes with respect to type and severity. The RD50 values (ppm) of the chemicals studied are as follows: 2,4-toluene diisocyanate (0.4), acrolein (1.7), formaldehyde (3.1), chloropicrin (8.0), chlorine (9.3), sulfur dioxide (117), ammonia (303), hydrogen chloride (309), dimethylamine (511), and epichlorohydrin (687). After exposure of mice for 6 hr/day for 5 days, the respiratory tract was examined for histopathologic changes. All irritants produced lesions in the nasal cavity with a distinct anterior-posterior severity gradient. There was considerable variation in the extent, and nature of the lesions. The lesions ranged from slight epithelial hypertrophy or hyperplasia to epithelial erosion, ulceration, and necrosis with variable inflammation of the subepithelial tissues. Only chlorine, chloropicrin, and epichlorohydrin induced lesions in the lower respiratory tract. These findings give additional support to the potential value of the RD50 model for setting occupational exposure guidelines and predicting the risk of injury to the respiratory tract from exposure to airborne sensory irritants.