Forskning
Udskriv Udskriv
Switch language
Rigshospitalet - en del af Københavns Universitetshospital
Udgivet

Acetaminophen metabolism revisited using non-targeted analyses: Implications for human biomonitoring

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Presence of parabens, phenols and phthalates in paired maternal serum, urine and amniotic fluid

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Long-term exposure to low levels of air pollution and mortality adjusting for road traffic noise: A Danish Nurse Cohort study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. CGRP-dependent signalling pathways involved in mouse models of GTN- cilostazol- and levcromakalim-induced migraine

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Paracetamol use during pregnancy - a call for precautionary action

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  3. Ocular Surface Microbiota in Contact Lens Users and Contact-Lens-Associated Bacterial Keratitis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Small RNAs in Seminal Plasma as Novel Biomarkers for Germ Cell Tumors

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

The analgesic paracetamol/acetaminophen (N-acetyl-4-aminophenol, APAP) is commonly used to relieve pain, fever and malaise. While sales have increased worldwide, a growing body of experimental and epidemiological evidence has suggested APAP as a possible risk factor for various health disorders in humans. To perform internal exposure-based risk assessment, the use of accurate and optimized biomonitoring methods is critical. However, retrospectively assessing pharmaceutical use of APAP in humans is challenging because of its short half-life. The objective of this study was to address the key issue of potential underestimation of APAP use using current standard analytical methods based on urinary analyses of free APAP and its phase II conjugates. The question we address is whether investigating additional metabolites than direct phase II conjugates could improve the monitoring of APAP. Using non-targeted analyses based on high-resolution mass spectrometry, we identified, in a controlled longitudinal exposure study with male volunteers, overlooked APAP metabolites with delayed formation and excretion rates. We postulate that these metabolites are formed via the thiomethyl shunt after the enterohepatic circulation as already observed in rodents. Importantly, these conjugated thiomethyl metabolites were (i) of comparable diagnostic sensitivity as the free APAP and its phase II conjugates detected by current methods; (ii) had delayed peak levels in blood and urine compared to other APAP metabolites and therefore potentially extend the window of exposure assessment; and (iii) provide relevant information regarding metabolic pathways of interest from a toxicological point of view. Including these metabolites in future APAP biomonitoring methods therefore provides an option to decrease potential underestimation of APAP use. Moreover, our data challenge the notion that the standard methods in biomonitoring based exclusively on the parent compound and its phase II metabolites are adequate for human biomonitoring of a non-persistent chemical such as APAP.

OriginalsprogEngelsk
Artikelnummer106388
TidsskriftEnvironment International
Vol/bind149
Sider (fra-til)1-11
Antal sider12
ISSN0160-4120
DOI
StatusUdgivet - apr. 2021

ID: 65605643