Journal article
Physiologically Based Pharmacokinetic Modeling of Salivary Concentrations for Noninvasive Biomonitoring of 2,4-Dichlorophenoxyacetic Acid (2,4-D)
Toxicological sciences, Vol.172(2), pp.330-343
12/01/2019
PMID: 31550007
Abstract
Saliva has become a favorable sample matrix for biomonitoring due to its noninvasive attributes and overall flexibility in collection. To ensure measured salivary concentrations reflect the exposure, a solid understanding of the salivary transport mechanism and relationships between salivary concentrations and other monitored matrices (ie, blood, urine) is needed. Salivary transport of a commonly applied herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D), was observed in vitro and in vivo and a physiologically based pharmacokinetic (PBPK) model was developed to translate observations from the cell culture model to those in animal models and further evaluate 2,4-D kinetics in humans. Although apparent differences in experimental in vitro and in vivo saliva:plasma ratios (0.034 and 0.0079) were observed, simulations with the PBPK model demonstrated dynamic time and dose-dependent saliva:plasma ratios, elucidating key mechanisms affecting salivary transport. The model suggested that 2,4-D exhibited diffusion-limited transport to saliva and was additionally impacted by protein binding saturation and permeability across the salivary gland. Consideration of sampling times post-exposure and potential saturation of transport mechanisms are then critical aspects for interpreting salivary 2,4-D biomonitoring observations. This work utilized PBPK modeling in in vitro to in vivo translation to explore benefits and limitations of salivary analysis for occupational biomonitoring.
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Details
- Title
- Physiologically Based Pharmacokinetic Modeling of Salivary Concentrations for Noninvasive Biomonitoring of 2,4-Dichlorophenoxyacetic Acid (2,4-D)
- Creators
- Alice A. Han - Pacific Northwest National LaboratoryCharles Timchalk - Pacific Northwest National LaboratoryZana A. Carver - Pacific Northwest National LaboratoryThomas J. Weber - Pacific Northwest National LaboratoryKimberly J. Tyrrell - Pacific Northwest National LaboratoryRyan L. Sontag - Pacific Northwest National LaboratoryTeresa Gibbins - Pacific Northwest National LaboratoryWilliam B. Chrisler - Pacific Northwest National LaboratoryKarl K. Weitz - Pacific Northwest National LaboratoryDan Du - Washington State UniversityYuehe Lin - Washington State UniversityJordan N. Smith - Pacific Northwest National Laboratory
- Publication Details
- Toxicological sciences, Vol.172(2), pp.330-343
- Academic Unit
- School of Mechanical and Materials Engineering
- Publisher
- Oxford Univ Press
- Number of pages
- 14
- Grant note
- R01 OH011023 / CDC/NIOSH grant; United States Department of Health & Human Services; Centers for Disease Control & Prevention - USA
- Identifiers
- 99901227638201842
- Language
- English
- Resource Type
- Journal article