Nasal Dosimetry, Lesion Distribution, and The Toxicologic Pathologist: A Brief Review

Abstract

The distribution of nasal lesions induced by xenobiotics is attributable to regional dosimetry, local tissue susceptibility, or a combination of these factors. Local tissue susceptibility is frequently related to site-specific xenobiotic metabolism, which also plays a role in the dose of parent compound, or toxic metabolite(s), delivered to individual cell populations in the nose. The toxicologic pathologist can provide valuable clues concerning the role of tissue dosimetry in nasal toxicity through recognition of lesion distribution patterns. Detection of such patterns may be achieved by the use of mapping strategies, combined with knowledge of factors that may account for dose-dependent site specificity of the responses observed. The regional dosimetry of xenobiotics is influenced by their physical and chemical properties. In the nose, interactions of xenobiotics with air, mucus, and blood flow, and the local metabolism also play a critical role. Integration of these factors with knowledge of lesion location provides insight for biologically based approaches to interspecies extrapolation and human risk estimation. Identification of target cell populations and characterization of the nature of disease processes observed are also an essential part of this process. During interpretation of nasal lesions and selection of responses for more detailed analyses directed toward quantitative human risk assessment, a disease-oriented approach is recommended. These issues are briefly reviewed here, with special reference to chemicals that induce nasal injury in rodents.