title: Sensory irritation response in rats: modeling, analysis and validation.
abstract: Inhaled gases can cause respiratory depression by irritating (stimulating) nerves in the nasal cavity. Respiratory depression, in turn, decreases the rate of delivery of those gases to the stimulated nerves, potentially leading to a complex feedback response. In order to better understand how the nervous system responds to such chemicals, a mathematical model is created to describe how the presence of irritants affects respiration in the rat. The ordinary differential equation model describes the dosimetry of these reactive gases in the respiratory tract, with particular focus on the physiology of the upper respiratory tract, and on the neurological control of respiration rate due to signaling from the irritant-responsive nerves in the nasal cavity. The ventilation equation is altered to account for an apparent change in dynamics between the initial ventilation decrease and the recovery to steady state as seen in formaldehyde exposure data. Further, the model is evaluated and improved through optimization of particular parameters to describe formaldehyde-induced respiratory response data and through sensitivity analysis. The model predicts the formaldehyde data well, and hence the model is thought to be a reasonable description of the physiological system of sensory irritation. The model is also expected to translate well to other irritants.
authors.affiliation: Center for Research in Scientific Computation and Department of Mathematics, North Carolina State University, Raleigh, NC, USA. yokley.karen@epa.gov
authors.forename: Karen A
authors.initials: KA
authors.lastname: Yokley
authors.forename: Hien
authors.initials: H
authors.lastname: Tran
authors.forename: Paul M
authors.initials: PM
authors.lastname: Schlosser
mesh_terms: D000818:Animals; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D025461:Feedback, Physiological; D005557:Formaldehyde / Q000633:toxicity; D005740:Gases / Q000633:toxicity; D007040:Hypoventilation / Q000209:etiology / Q000503:physiopathology / Q000662:veterinary; D019570:Inhalation Exposure; D007509:Irritants / Q000633:toxicity*; D008954:Models, Biological; D046569:Neuroepithelial Cells / Q000187:drug effects / Q000502:physiology; D012123:Pulmonary Ventilation / Q000187:drug effects; D051381:Rats; D012119:Respiration / Q000187:drug effects*; D012137:Respiratory System / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology; D012677:Sensation / Q000187:drug effects* / Q000502:physiology; D014276:Trigeminal Nerve / Q000187:drug effects / Q000503:physiopathology
chemical_list: D005740:Gases; D007509:Irritants; D005557:Formaldehyde