title: Development of a rhesus monkey lung geometry model and application to particle deposition in comparison to humans.
abstract: The exposure-dose-response characterization of an inhalation hazard established in an animal species needs to be translated to an equivalent characterization in humans relative to comparable doses or exposure scenarios. Here, the first geometry model of the conducting airways for rhesus monkeys is developed based upon CT images of the conducting airways of a 6-month-old male, rhesus monkey. An algorithm was developed for adding the alveolar region airways using published rhesus morphometric data. The resultant lung geometry model can be used in mechanistic particle or gaseous dosimetry models. Such dosimetry models require estimates of the upper respiratory tract volume of the animal and the functional residual capacity, as well as of the tidal volume and breathing frequency of the animal. The relationship of these variables to rhesus monkeys of differing body weights was established by synthesizing and modeling published data as well as modeling pulmonary function measurements on 121 rhesus control animals. Deposition patterns of particles up to 10 µm in size were examined for endotracheal and and up to 5 µm for spontaneous breathing in infant and young adult monkeys and compared to those for humans. Deposition fraction of respirable size particles was found to be higher in the conducting airways of infant and young adult rhesus monkeys compared to humans. Due to the filtering effect of the conducting airways, pulmonary deposition in rhesus monkeys was lower than that in humans. Future research areas are identified that would either allow replacing assumptions or improving the newly developed lung model.
authors.affiliation: Applied Research Associates, Inc., 8537 Six Forks Road, Suite 600, Raleigh, NC 27615-2963, USA. basgharian@ara.com
authors.forename: Bahman
authors.initials: B
authors.lastname: Asgharian
authors.forename: Owen
authors.initials: O
authors.lastname: Price
authors.forename: Gene
authors.initials: G
authors.lastname: McClellan
authors.forename: Rick
authors.initials: R
authors.lastname: Corley
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Einstein
authors.forename: Richard E
authors.initials: RE
authors.lastname: Jacob
authors.forename: Jack
authors.initials: J
authors.lastname: Harkema
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Carey
authors.forename: Edward
authors.initials: E
authors.lastname: Schelegle
authors.forename: Dallas
authors.initials: D
authors.lastname: Hyde
authors.forename: Julia S
authors.initials: JS
authors.lastname: Kimbell
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Miller
mesh_terms: D000280:Administration, Inhalation; D000465:Algorithms; D000818:Animals; D005260:Female; D006801:Humans; D008253:Macaca mulatta / Q000033:anatomy & histology* / Q000502:physiology; D008297:Male; D023421:Models, Animal; D008954:Models, Biological; D010316:Particle Size; D052638:Particulate Matter / Q000378:metabolism; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000033:anatomy & histology* / Q000378:metabolism
chemical_list: D052638:Particulate Matter