title: Dosimetry of nasal uptake of water-soluble and reactive gases: a first study of interhuman variability.
abstract: Certain inhaled chemicals, such as reactive, water-soluble gases, are readily absorbed by the nasal mucosa upon inhalation and may cause damage to the nasal epithelium. Comparisons of the spatial distribution of nasal lesions in laboratory animals exposed to formaldehyde with gas uptake rates predicted by computational models reveal that lesions usually occur in regions of the susceptible epithelium where gas absorption is highest. Since the uptake patterns are influenced by air currents in the nose, interindividual variability in nasal anatomy and ventilation rates due to age, body size, and gender will affect the patterns of gas absorption in humans, potentially putting some age groups at higher risk when exposed to toxic gases. In this study, interhuman variability in the nasal dosimetry of reactive, water-soluble gases was investigated by means of computational fluid dynamics (CFD) models in 5 adults and 2 children, aged 7 and 8 years old. Airflow patterns were investigated for allometrically scaled inhalation rates corresponding to resting breathing. The spatial distribution of uptake at the airway walls was predicted to be nonuniform, with most of the gas being absorbed in the anterior portion of the nasal passages. Under the conditions of these simulations, interhuman variability in dose to the whole nose (mass per time per nasal surface area) due to differences in anatomy and ventilation was predicted to be 1.6-fold among the 7 individuals studied. Children and adults displayed very similar patterns of nasal gas uptake; no significant differences were noted between the two age groups.
authors.affiliation: The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Guilherme J M
authors.initials: GJ
authors.lastname: Garcia
authors.forename: Jeffry D
authors.initials: JD
authors.lastname: Schroeter
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Segal
authors.forename: John
authors.initials: J
authors.lastname: Stanek
authors.forename: Gary L
authors.initials: GL
authors.lastname: Foureman
authors.forename: Julia S
authors.initials: JS
authors.lastname: Kimbell
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D005740:Gases / Q000008:administration & dosage* / Q000737:chemistry*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009296:Nasal Cavity / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D009297:Nasal Mucosa / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D012995:Solubility / Q000187:drug effects; D014867:Water / Q000737:chemistry*
chemical_list: D005740:Gases; D014867:Water