CORRELATION OF REGIONAL FORMALDEHYDE FLUX PREDICTIONS WITH THE DISTRIBUTION OF FORMALDEHYDE-INDUCED SQUAMOUS METAPLASIA IN F344 RAT NASAL PASSAGES

Squamous epithelium lines the nasal vestibule of the rat, rhesus monke y, and human. Respiratory, transitional, and olfactory epithelia line most areas posterior to the nasal vestibule, Inhaled formaldehyde gas induces squamous metaplasia posterior to the nasal vestibule and does not induce lesions in the nasal vestibule in rats and rhesus monkeys, indicating that squamous epithelium is resistant to irritant effects o f formaldehyde and that squamous metaplasia may be an adaptive respons e. If squamous metaplasia is determined by formaldehyde dosimetry rath er than by tissue-specific factors, squamous epithelium may be protect ive by absorbing less formaldehyde than other epithelial types. In a p revious study, a three-dimensional, anatomically accurate computationa l fluid dynamics (CFD) model of the anterior F344 rat nasal passages w as used to simulate inspiratory airflow and inhaled formaldehyde trans port. The present study consisted of two related parts. First, the rat CFD model was used to test the hypothesis that the distribution of fo rmaldehyde-induced squamous metaplasia is related to the location of h igh-flux regions posterior to squamous epithelium. Regional formaldehy de flux into nonsquamous epithelium predicted by the CFD model correla ted with regional incidence of formaldehyde-induced squamous metaplasi a on the airway perimeter of one cross-sectional level of the noses of F344 rats exposed to 10 and 15 ppm formaldehyde gas for 6 months. For maldehyde flux into nonsquamous epithelium was estimated to vary by an order of magnitude depending on the degree of formaldehyde absorption by squamous epithelium. These results indicate that the degree to whi ch squamous epithelium absorbs formaldehyde strongly affects the rate and extent of the progression of squamous metaplasia with continued ex posure to formaldehyde. In the second part of this study, the CFD mode l was used to predict squamous metaplasia progression. Data needs for verification of this model prediction are considered. These results in dicate that information on the permeability of squamous epithelium in rats,: monkeys, and humans is important for accurate prediction of upt ake in regions posterior to the nasal vestibule. (C) 1997 Elsevier Sci ence B.V.