UPPER RESPIRATORY-TRACT SURFACE-AREAS AND VOLUMES OF LABORATORY-ANIMALS AND HUMANS - CONSIDERATIONS FOR DOSIMETRY MODELS

To facilitate the development of regional respiratory tract dosimetry comparisons between laboratory animal species and humans, published su rface area (SA) and volume (VOL) data for the upper respiratory tract (URT) were reviewed. The review of the literature revealed that (1) di fferent studies used different techniques to prepare specimens and mak e measurements, (2) different areas of the URT were measured, and (3) URT surface areas and volumes have been reported for a limited number of individual subjects within a species but for a relatively wide rang e of species. The published data are summarized in tables in this arti cle. New measurements made in an F344 rat and in a female human subjec t are also presented. Despite the differences in experimental protocol s, it was possible to fit allometric scaling equations to the data: In (SA, cm(2)) = -0.34 + 0.52 ln(body weight, g) and ln(VOL, cm(3)) = 1.7 0 + 0.78 In(body weight, g). Separate scaling equations Mere also fitt ed for rats alone. To illustrate the use of these scaling equations in quantitative human health risk assessment, two dose metrics (fraction al absorption/cm(2) URT SA and fractional absorption/g body weight) fo r predicted URT uptake in laboratory animals and humans were calculate d for acrolein and epichlorohydrin. Expressed as an animal-to-human ra tio, the 95% confidence interval for URT SA could change the predicted dose ratio by up to a :actor of 2. Additional studies are needed to d escribe the entire URT (from the nares through the larynx) quantitativ ely and to decrease variability in scaling equation predictions as wel l as to develop additional species-specific scaling equations. Three-d imensional imaging techniques provide a noninvasive method to obtain U RT surface areas and volumes in humans and the larger laboratory anima ls. Comparisons of magnetic resonance image (MRI) and computed tomogra phy (CT) scans made as part of this study suggest that the greater cla rity of the mucosal-air interface in the CT image provides better reso lution for the study of anatomic features. Because there is no radiati on exposure associated with MRI imaging, however, it is more safely us ed than CT scans in making repealed measurements in a subject to eluci date changes in URT geometry associated with normal nasal cycling or o ther physiological changes.