Derivation of first-order dissolution rates to estimate particle clearance and burden in the human respiratory tract
Abstract Inhalation is a portal-of-entry for aerosols via the respiratory tract where particulate burden accumulates depending on sites of particle deposition, normal clearance mechanisms, and particle solubility. The time available for dissolution of particles is determined by the balance between t...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-04-01
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| Series: | Particle and Fibre Toxicology |
| Online Access: | https://doi.org/10.1186/s12989-023-00523-z |
| _version_ | 1797836659475087360 |
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| author | James S. Brown Gary L. Diamond |
| author_facet | James S. Brown Gary L. Diamond |
| author_sort | James S. Brown |
| collection | DOAJ |
| description | Abstract Inhalation is a portal-of-entry for aerosols via the respiratory tract where particulate burden accumulates depending on sites of particle deposition, normal clearance mechanisms, and particle solubility. The time available for dissolution of particles is determined by the balance between the rate of particle clearance from a region and their solubility in respiratory solvents. Dissolution is a function of particle surface area divided by particle volume or mass (i.e., dissolution is inversely proportional to the physical diameter of particles). As a conservative approach, investigators commonly assume the complete and instantaneous dissolution of metals from particles depositing in the alveolar region of the respiratory tract. We derived first-order dissolution rate constants to facilitate biokinetic modeling of particle clearance, dissolution, and absorption into the blood. We then modeled pulmonary burden and total dissolution of particles over time as a function of particle size, density, and solubility. We show that assuming poorly soluble particle forms will enter the blood as quickly as highly soluble forms causes an overestimation of concentrations of the compound of interest in blood and other extrapulmonary tissues while also underestimating its pulmonary burden. We conclude that, in addition to modeling dose rates for particle deposition into the lung, physiologically based pharmacokinetic modeling of pulmonary and extrapulmonary tissues concentrations of moderately and poorly soluble materials can be improved by including estimates of lung burden and particle dissolution over time. |
| first_indexed | 2024-04-09T15:13:34Z |
| format | Article |
| id | doaj.art-0dcf2145ef4b4a3598dd4c1099ebe8ec |
| institution | Directory Open Access Journal |
| issn | 1743-8977 |
| language | English |
| last_indexed | 2024-04-09T15:13:34Z |
| publishDate | 2023-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Particle and Fibre Toxicology |
| spelling | doaj.art-0dcf2145ef4b4a3598dd4c1099ebe8ec2023-04-30T11:02:55ZengBMCParticle and Fibre Toxicology1743-89772023-04-0120111910.1186/s12989-023-00523-zDerivation of first-order dissolution rates to estimate particle clearance and burden in the human respiratory tractJames S. Brown0Gary L. Diamond1U.S. Environmental Protection Agency, Office of Research and DevelopmentSRC, Inc.Abstract Inhalation is a portal-of-entry for aerosols via the respiratory tract where particulate burden accumulates depending on sites of particle deposition, normal clearance mechanisms, and particle solubility. The time available for dissolution of particles is determined by the balance between the rate of particle clearance from a region and their solubility in respiratory solvents. Dissolution is a function of particle surface area divided by particle volume or mass (i.e., dissolution is inversely proportional to the physical diameter of particles). As a conservative approach, investigators commonly assume the complete and instantaneous dissolution of metals from particles depositing in the alveolar region of the respiratory tract. We derived first-order dissolution rate constants to facilitate biokinetic modeling of particle clearance, dissolution, and absorption into the blood. We then modeled pulmonary burden and total dissolution of particles over time as a function of particle size, density, and solubility. We show that assuming poorly soluble particle forms will enter the blood as quickly as highly soluble forms causes an overestimation of concentrations of the compound of interest in blood and other extrapulmonary tissues while also underestimating its pulmonary burden. We conclude that, in addition to modeling dose rates for particle deposition into the lung, physiologically based pharmacokinetic modeling of pulmonary and extrapulmonary tissues concentrations of moderately and poorly soluble materials can be improved by including estimates of lung burden and particle dissolution over time.https://doi.org/10.1186/s12989-023-00523-z |
| spellingShingle | James S. Brown Gary L. Diamond Derivation of first-order dissolution rates to estimate particle clearance and burden in the human respiratory tract Particle and Fibre Toxicology |
| title | Derivation of first-order dissolution rates to estimate particle clearance and burden in the human respiratory tract |
| title_full | Derivation of first-order dissolution rates to estimate particle clearance and burden in the human respiratory tract |
| title_fullStr | Derivation of first-order dissolution rates to estimate particle clearance and burden in the human respiratory tract |
| title_full_unstemmed | Derivation of first-order dissolution rates to estimate particle clearance and burden in the human respiratory tract |
| title_short | Derivation of first-order dissolution rates to estimate particle clearance and burden in the human respiratory tract |
| title_sort | derivation of first order dissolution rates to estimate particle clearance and burden in the human respiratory tract |
| url | https://doi.org/10.1186/s12989-023-00523-z |
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