Reliable determination of the main metabolites of 2-phenoxyethanol in human blood and urine using LC-MS/MS analysis

Jäger, Thomas; Eckert, Elisabeth; Leibold, Edgar; Bader, Michael

doi:10.1039/d2ay01407f

Cited by 5 publications

(5 citation statements)

References 18 publications

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“…Thus, all analyses were done without an additional hydrolysis step (cf. Jäger et al 2022 ). Unmetabolized PhE and 4-OH-PhE were determined using GC-PCI-MS/MS-analysis following liquid–liquid extraction and silylation.…”

Section: Methodsmentioning

confidence: 99%

“…The analytical determination was done according to previous published procedures by Jäger et al ( 2022 , 2024 ). Thus, all reagents and chemicals used as well as the applied sample preparation procedures and the instrumentation used is described in detail there.…”

Section: Methodsmentioning

confidence: 99%

“…due to their toxicity or their relevance for consumer exposure, by establishing reliable human biomonitoring methods and to investigate the biotransformation pathways including the main toxicokinetic parameters of the substances of interest. Thus, recently, biomonitoring methods for the determination of PhE and its metabolites in human blood and urine were developed (Jäger et al 2022 , 2024 ). In this context, background levels of PhE and further potential PhE metabolites, namely 4-OH-PhE (4-hydroxy-phenoxyethanol) and 4-OH-PhAA (4-hydroxy-phenoxyacetic acid), were assessed for the first time in human blood and urine, respectively.…”

Section: Introductionmentioning

confidence: 99%

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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: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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

Self Cite

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“…30 It is widely used in food analysis, 31,32 environmental analysis 33,34 and detection of other complex matrix residues. [35][36][37] These extraction-based pre-treatment methods have been considerably successful; however, they use large amounts of consumables and are expensive to operate. The use of large amounts of toxic organic solvents (such as chloroform, dichloromethane, or other organic solvents for liquid-liquid extraction) is also environmentally concerning.…”

Section: Introductionmentioning

confidence: 99%

“…30 It is widely used in food analysis, 31,32 environmental analysis 33,34 and detection of other complex matrix residues. 35–37…”

Section: Introductionmentioning

confidence: 99%

Solid phase extraction technology combined with UPLC-MS/MS: a method for detecting 20 β-lactamase antibiotics traces in goat's milk

He,

Li,

et al. 2024

Anal. Methods

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Dermal penetration of 2-phenoxyethanol in humans: in vivo metabolism and toxicokinetics

Eckert,

Jäger,

Leibold

et al. 2024

Arch Toxicol

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Abstract2-Phenoxyethanol (PhE) is an amphiphilic organic compound frequently used as a broad-spectrum preservative in cosmetic products and other consumer goods. PhE is also used as a biocidal component in occupational settings. A previous volunteer study by our working group following oral exposure to PhE showed that PhE is almost completely taken up into the human body followed by an extensive metabolization and fast urinary elimination. However, with respect to the importance of transdermal uptake, we now conducted another volunteer study applying dermal PhE exposure: five volunteers were dermally exposed with 0.4 mg/kg body weight of PhE each on a specified 800 cm2 skin area using non-occlusive conditions. Subsequently, blood and urine samples were collected up to 48 h post-exposure. The present study illustrates the fast transdermal uptake of PhE. Following systemic resorption, PhE was extensively metabolized and rapidly eliminated in urine mainly in form of the metabolites PhAA (phenoxyacetic acid) and 4-OH-PhAA (4-hydroxyphenoxyacetic acid) accounting together for over 99% of the renally excreted PhE dose. The absolute urinary recovery rate of PhE was observed to be significantly lower following dermal exposure compared to oral uptake indicating a dermal resorption rate of PhE of about 45% in humans. The present study provides for the first time detailed insights into human biotransformation and toxicokinetics of PhE after dermal exposure, thus establishing a reliable strategy for human biomonitoring of PhE. The here presented results may thus be useful for further toxicokinetic modeling and forward dosimetry.

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Reliable determination of the main metabolites of 2-phenoxyethanol in human blood and urine using LC-MS/MS analysis

Abstract: 2-Phenoxyethanol (PhE) is used as a broad-spectrum preservative in several consumer products like cosmetics and cleaning agents. To enable the analysis and assessment of human exposure to PhE, a fast...

Cited by 5 publications

References 18 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

Solid phase extraction technology combined with UPLC-MS/MS: a method for detecting 20 β-lactamase antibiotics traces in goat's milk

Dermal penetration of 2-phenoxyethanol in humans: in vivo metabolism and toxicokinetics

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