Knowledge of patterns of lesion distribution can provide insight into the relative roles played by regional tissue dose and local tissue susceptibility in toxic responses to xenobiotics in the nose and assist assessment of potential human risk. A consistent approach is needed for recording lesion distribution patterns in the complex nasal airways of rats and mice. The present work provides a series of diagrams of the nasal passages of the Fischer-344 rat and B6C3F1 mouse, designed for mapping nasal lesions. The diagrams present each of the major cross-sectional airway profiles, provide adequate space for nasal mucosal lesion recording, and are suitable for duplication in a commercial photocopier. Sagittal diagrams are also provided to permit transfer of lesion location data observed in transverse sections onto the long axis of the nose. The distribution of lesions induced by a selected range of xenobiotics is presented. Approaches to application of the diagrams and interpretation of results obtained are discussed in relation to factors responsible for lesion distribution in the nose and their relevance to interspecies extrapolation. A modified approach to anatomical classification of the ethmoturbinates of the rodent is also presented.
Recently, finite-element computer simulation of airflow in rat nasal airways has been used to predict local and global xenobiotic mass transport. These computer simulations have the capability to facilitate the extrapolation of experimentat data from rats to humans for risk assessment. lmplementation of similar models of other species requires accurate and detailed geometrical coordinates of airways. This article presents a sectioning method for the acquisition of airway coordinates and morphometric data from fixed tissues. Using this method, airway tissue specimens are embedded in a frozen, contrast-enhancing medium and serially sectioned. Video imager are digitized from photographs of the block face, and image analysis is used to obtain geometrical coordinates of the nasal passage perimeters. Calibration images and embedded alignment marks are used to scale and align sequentiaf sections. Data resulting from the application of this method to a rhesus monkey specimen are reported, including a three-dimensional computer reconstruction of the data. Airway coordinates are also used to generate a set of diagrams suitable for lesion mapping for comparison w i t h local dosimetry data derived from numerical simulations. This method improves on previously reported methods. Undistorted airway geometry is obtained by photographing the cut block face. Automatic thresholding to obtain coordinates during image analysis is made possible by the contrast-enhancing medium. Automatic scaling and alignment of sections is facilitated by the use of calibration images and alignment marks. This coordinate acquisition method has applicability to other complex biological passageways.Understanding the effects of toxic agents requires knowledge of the dose delivered to the target tissue, but the dose is often difficult to quantify accurately for toxic agents that are inhaled. Time-dependent airflow patterns, mucociliary translocation, the uptake characteristics of different epithelial types, and local metabolism all have the potential to influence local xenobiotic disposition (Morgan, 1994). Recent work investigating the dosimetric
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