Application of Computational Fluid Dynamics to Regional Dosimetry of Inhaled Chemicals in the Upper Respiratory Tract of the Rat

Kimbell, Julia S.; Gross, Elizabeth A.; Joyner, Donald R.; Godo, Matthew N.; Morgan, Kevin T.

doi:10.1006/taap.1993.1152

Cited by 166 publications

(78 citation statements)

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“…Previous studies examining the susceptibility of the nasal mucosa of rats have shown that the formaldehyde mass flux predicted by computer fluid dynamics techniques correlates with both the patterns of nonolfactory mucosal injury from inhaled formaldehyde (Kimbell et al, 1993) and the sites of DNA-protein cross-linking induced by inhaled formaldehyde (Hubal et al, 1997). Hardisty et al (1999) have found that eight toxicants (propylene glycol monomethyl ether acetate, n-butyl propionate, ethyl acetate, n-butyl acetate, dibasic esters, primary amyl acetate, vinyl acetate, and methyl methacrylate) result in a consistent pattern of olfactory mucosal injury after inhalation exposure, regardless of concentration and duration of exposure.…”

Section: Discussionmentioning

confidence: 99%

In Situ Naphthalene Bioactivation and Nasal Airflow Cause Region-Specific Injury Patterns in the Nasal Mucosa of Rats Exposed to Naphthalene by Inhalation

Lee¹,

Phimister²,

Morin³

et al. 2005

J Pharmacol Exp Ther

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Despite the fact that naphthalene (NA), a volatile, ubiquitous air pollutant, was recently identified as a probable human carcinogen, little is known about nasal cytotoxicity from inhaled NA. To define and compare acute nasal injury from inhalation and systemic NA exposures, male Sprague-Dawley rats were exposed to filtered air; 3.4 or 23.8 ppm NA by inhalation for 4 h; or to 0, 25, 50, 100, or 200 mg/kg NA via intraperitoneal injection. Severe cellular injury occurred exclusively in the olfactory mucosa 24 h postinhalation exposure to 3.4 ppm NA for 4 h. This level is significantly below both the current Occupational Safety and Health Administration standard (10 ppm; 8 h) for NA and the lowest observed adverse effect level (10 ppm; 2 years) for the incidence of rat olfactory neoplasms. Injury within the olfactory mucosa from inhaled NA was confined to the medial meatus, whereas systemic NA generated severe injury throughout the olfactory region. The pattern of nasal injury from inhaled NA in this study is consistent with previous studies of nasal airflow simulation within the olfactory region. The nonolfactory mucosa on the nasal septum, a high airflow region, metabolized naphthalene slowly, whereas the olfactory regions of the nasal septum and ethmoturbinates metabolized this substrate at high rates. This study concludes that 1) the incidence of acute nasal injury from systemic and inhaled NA correlates with the rates of regional microsomal NA metabolism and that 2) the nasal airflow pattern determines the pattern of olfactory mucosal injury from inhaled NA.

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Section: Discussionmentioning

confidence: 99%

In Situ Naphthalene Bioactivation and Nasal Airflow Cause Region-Specific Injury Patterns in the Nasal Mucosa of Rats Exposed to Naphthalene by Inhalation

Lee¹,

Phimister²,

Morin³

et al. 2005

J Pharmacol Exp Ther

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“…Gender Again using CO 2 as stimulus and the reflex apnea as the outcome, it has been shown that females are 14 to 30% more sensitive than males to nasal pungency whether evoked unilaterally or bilaterally. 151,152 Nasal detection thresholds for CO 2 have also been found to be lower for females than for males. 205 Further experiments employing a magnitude matching technique (see section V. A.…”

Section: B Subject Characteristics I Smoking Behaviormentioning

confidence: 99%

“…The degree to which concentrationresponse relationships from animal data are applicable to humans is also questionable, not only 7 in terms of biosynthetic pathways within the olfactory mucosa, 1 but because, unlike humans, most mice, rats, and rabbits are obligate nose breathers and have more complex nasal passages. 2,3 For example, the ethmoidal turbinates are greater in number and more complex in rodents than in humans, appearing in double, rather than single, rows. These differences are important, as the turbinates, in large measure, determine the pattern and nature of deposition of inhaled chemicals within the nasal passages.…”

Section: Introductionmentioning

confidence: 99%

Assessment of Upper Respiratory Tract and Ocular Irritative Effects of Volatile Chemicals in Humans

Doty

Cometto‐Muñiz

Jalowayski

et al. 2004

Critical Reviews in Toxicology

131

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“…CFD modeling proceeds in several steps: (1) selecting (or writing) software; (2) defining the boundary (airway walls) conditions; (3) solving airflow fields (by an iteration/convergence process); (4) selecting aerosol particle properties; (5) placing the particles into the airway entrances; and (6) defining particle deposition sites (where particle trajectories intersect airway walls). CFD models for calculating detailed particle deposition in the respiratory tract that emerged in the 1990s represented an important advance (Balásházy & Hofmann, 1993;Ferron et al, 1991;Kimbell, Gross, Joyner, Godo, & Morgan, 1993;Yu, Zhang, & Lessmann, 1996). Kimbell and colleagues were probably the first to mesh a three-dimensional respiratory tract structure used to model the gas flow (in the nose of the rat).…”

Section: Computational Fluid Dynamics Models Of Inhaled Particle Depomentioning

confidence: 99%

The evolution of inhaled particle dose modeling: A review

Phalen

Raabe

2016

Journal of Aerosol Science

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a b s t r a c tInhaled aerosol dose models play critical roles in medicine, the regulation of air pollutants and basic research. The models fall into several categories: traditional, computational fluid dynamical (CFD), physiologically based pharmacokinetic (PBPK), empirical, semi-empirical, and "reference". Each type of model has its strengths and weaknesses, so multiple models are commonly used for practical applications. Aerosol dose models combine information on aerosol behavior and the anatomy and physiology of exposed human and laboratory animal subjects. Similar models are used for in-vitro studies. Several notable advances have been made in aerosol dose modeling in the past 80 years. The pioneers include Walter Findeisen, who in 1935 published the first traditional model and established the structure of modern models. His model combined aerosol behavior with simplified respiratory tract structures. Ewald Weibel established morphometric techniques for the lung in 1963 that are still used to develop data for modeling today. Advances in scanning techniques have similarly contributed to the knowledge of respiratory tract structure and its use in aerosol dose modeling. Several scientists and research groups have developed and advanced traditional, CFD, and PBPK models. Current issues under study include understanding individual and species differences; examining localized particle deposition; modeling non-ideal aerosols and nanoparticle behavior; linking the regions of the respiratory tract airways from nasal-oral to alveolar; and developing sophisticated supporting software. Although a complete history of inhaled aerosol dose modeling is far too extensive to cover here, selected highlights are described in this paper.

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Application of Computational Fluid Dynamics to Regional Dosimetry of Inhaled Chemicals in the Upper Respiratory Tract of the Rat

Cited by 166 publications

References 0 publications

In Situ Naphthalene Bioactivation and Nasal Airflow Cause Region-Specific Injury Patterns in the Nasal Mucosa of Rats Exposed to Naphthalene by Inhalation

In Situ Naphthalene Bioactivation and Nasal Airflow Cause Region-Specific Injury Patterns in the Nasal Mucosa of Rats Exposed to Naphthalene by Inhalation

Assessment of Upper Respiratory Tract and Ocular Irritative Effects of Volatile Chemicals in Humans

The evolution of inhaled particle dose modeling: A review

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