Pharmacokinetics of 2-phenoxyethanol and its major metabolite, phenoxyacetic acid, after dermal and inhaled routes of exposure: application to development PBPK model in rats

Kwon, Mi‐Hye; Park, Jung Bae; Kwon, Miwha; Song, Jin-Ho; Yeo, Chang Su; Bae, Soo Hyeon

doi:10.1007/s00204-021-03041-z

Cited by 4 publications

(2 citation statements)

References 28 publications

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“…Furthermore, the urinary recovery rate following dermal exposure was observed to be significantly lower by a factor of about 2 compared to oral exposure probably due to a reduced dermal resorption rate of PhE. The bioavailability rate of PhE after single dermal exposure of about 40% is well in the range of dermal resorption rates reported or predicted by other studies (SCCS 2016 ; Kwon et al 2021 ). However, in an animal study using occlusive dermal PhE application, a higher resorption rate of about 75% was observed (Kim et al 2015 ).…”

Section: Discussionsupporting

confidence: 65%

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Biotransformation and toxicokinetics of 2-phenoxyethanol after oral exposure in humans: a volunteer study

Eckert,

Jäger,

Hiller

et al. 2024

Arch Toxicol

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Abstract2-Phenoxyethanol (PhE) is an aromatic glycol ether and is used in a variety of functions and applications, e.g., as preservative in pharmaceuticals, cosmetic and personal care products, as biocide in disinfectants (e.g. human hygiene), or as a solvent in formulations (e.g. coatings, functional fluids). Despite its widespread use, little is yet known on its biotransformation and toxicokinetics in humans. Therefore, a pilot study was conducted with oral administration of PhE (5 mg/kg body weight) to five volunteers. Blood and urine samples were collected and analyzed for PhE and three of its presumed metabolites up to 48 h post-exposure. Additionally, one volunteer was dermally exposed to PhE and monitored until 72 h post-exposure. PhE was rapidly resorbed following both oral and dermal application with tmax-levels in blood of about 1 h and 3 h, respectively. Metabolism of PhE was observed to be rather extensive with phenoxyacetic acid (PhAA) and 4-hydroxyphenoxyacetic acid (4-OH-PhAA) as the main metabolites found in blood and urine following oral and dermal exposure. PhE was excreted rapidly and efficiently via urine mostly in metabolized form: following oral exposure, on average 77% and 12% of the applied dose was excreted within 48 h as PhAA and 4-OH-PhAA, respectively. A similar metabolism pattern was observed following the single dermal exposure experiment. The obtained data on biotransformation and toxicokinetics of PhE in humans provide valuable information on this important chemical and will be highly useful for pharmacokinetic modelling and evaluation of human PhE exposure.

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Section: Discussionsupporting

confidence: 65%

“…Recently, several studies focused on PBPK modelling to predict tissue and urine concentration of PhE following oral, dermal or inhalation exposure (Kwon et al 2021 ; Troutman et al 2015 ; Zhang et al 2022 ). The results, however, vary considerably and leave many issues unresolved.…”

Section: Introductionmentioning

confidence: 99%

Biotransformation and toxicokinetics of 2-phenoxyethanol after oral exposure in humans: a volunteer study

Eckert,

Jäger,

Hiller

et al. 2024

Arch Toxicol

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Physiologically-based toxicokinetic modeling of human dermal exposure to diethyl phthalate: Application to health risk assessment

Zhang

Zhan

et al. 2022

Chemosphere

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Prediction of tissue and urine concentrations of 2-phenoxyethanol and its metabolite 2-phenoxyacetic acid in rat and human after oral and dermal exposures via GastroPlus^TM physiologically based pharmacokinetic modelling

Zhang

LeBaron

Marty

2022

SAR and QSAR in Environmental Research

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Pharmacokinetics of 2-phenoxyethanol and its major metabolite, phenoxyacetic acid, after dermal and inhaled routes of exposure: application to development PBPK model in rats

Cited by 4 publications

References 28 publications

Biotransformation and toxicokinetics of 2-phenoxyethanol after oral exposure in humans: a volunteer study

Biotransformation and toxicokinetics of 2-phenoxyethanol after oral exposure in humans: a volunteer study

Physiologically-based toxicokinetic modeling of human dermal exposure to diethyl phthalate: Application to health risk assessment

Prediction of tissue and urine concentrations of 2-phenoxyethanol and its metabolite 2-phenoxyacetic acid in rat and human after oral and dermal exposures via GastroPlus^TM physiologically based pharmacokinetic modelling

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Pharmacokinetics of 2-phenoxyethanol and its major metabolite, phenoxyacetic acid, after dermal and inhaled routes of exposure: application to development PBPK model in rats

Cited by 4 publications

References 28 publications

Biotransformation and toxicokinetics of 2-phenoxyethanol after oral exposure in humans: a volunteer study

Biotransformation and toxicokinetics of 2-phenoxyethanol after oral exposure in humans: a volunteer study

Physiologically-based toxicokinetic modeling of human dermal exposure to diethyl phthalate: Application to health risk assessment

Prediction of tissue and urine concentrations of 2-phenoxyethanol and its metabolite 2-phenoxyacetic acid in rat and human after oral and dermal exposures via GastroPlusTM physiologically based pharmacokinetic modelling

Contact Info

Product

Resources

About

Prediction of tissue and urine concentrations of 2-phenoxyethanol and its metabolite 2-phenoxyacetic acid in rat and human after oral and dermal exposures via GastroPlus^TM physiologically based pharmacokinetic modelling