Dosimetry modeling of inhaled formaldehyde: Comparisons of local flux predictions in the rat, monkey, and human nasal passages

Formaldehyde-induced nasal squamous cell carcinomas in rats and squamous me taplasia in rats and rhesus monkeys occur in specific regions of the nose w ith species-specific distribution patterns. Experimental approaches address ing local differences in formaldehyde uptake patterns and dose are limited by the resolution of dissection techniques used to obtain tissue samples an d the rapid metabolism of absorbed formaldehyde in the nasal mucosa. Anatom ically accurate, 3-dimensional computational fluid dynamics models of F344 rat, rhesus monkey, and human nasal passages were used to estimate and comp are regional inhaled formaldehyde uptake patterns predicted among these spe cies. Maximum flux values, averaged over a breath, in nonsquamous epitheliu m were estimated to be 2620, 4492, and 2082 pmol/(mm(2)-ppm) in the rat, mo nkey, and human respectively. Flux values predicted in sites where cell pro liferation rates were measured as similar in rats and monkeys were also sim ilar, as were fluxes predicted in a region of high tumor incidence in the r at nose and the anterior portion of the human nose. Regional formaldehyde f lux estimates are directly applicable to clonal growth modeling of formalde hyde carcinogenesis to help reduce uncertainty in human cancer risk estimat es.