Assessment of Complex Mixture Inhalation in the Upper Respiratory Tract of Laboratory Animals

Introduction Remarks

These manuscripts represent the published account of two symposia dealing with the nose and upper respiratory tract of laboratory animal species, predominantly the rodent. They were presented at the 24th and 25th Annual Meetings of the American College of Toxicology. The purpose was to direct attention to the response of the nose and upper airways to toxic injury related to inhalation of complex mixtures and quantification of that response. Mixtures of a complex nature are more common inhalants for humans than a pure chemical, whether formatted as a pharmaceutical product, or inhaled as a toxic by-product. The effect of a complex may differ from an individual chemical itself. This was shown in the Wistar rat, wherein the rats were exposed to various aldehydes alone, or together in a mixture. Based on pathomorphologic changes and cell proliferation in the nose, mixtures of the aldehydes were more severe and extensive in both the respiratory and olfactory epithelium than those observed following exposure to comparable levels of the individual chemicals (Monticello and Morgan, 1997). Since the upper respiratory tract is a multiplex organ, the distribution of lesions is generally a consequence of the susceptibility of the tissues in the various regions of the respiratory tract, and the deposition of the chemical into these regions (Morgan and Monticello, 1990). The latter is influenced by airflow and fluid dynamics of the upper respiratory tract (Frederick et al., 2001). Lesion development is dependent on numerous factors including the properties of the chemicals, solubility, absorption, concentration and length of exposure, particulate materials, and effects of nasal secretions, chemical metabolism, and vasculature (Morgan and Monticello, 1990).

The manuscripts that follow deal with the complex functional anatomy of these organs and their response to injury, the effect of airflow on deposition of materials, the molecular assessment of the olfactory epithelium to injury, and stereological concepts and applications used to quantify the response to injury.