Ubiquitous presence of paracetamol in human urine: sources and implications

Modick, Hendrik; Weiß, Tobias; Dierkes, Georg; Brüning, Thomas; Koch, Holger M.

doi:10.1530/rep-13-0527

Cited by 48 publications

(53 citation statements)

References 45 publications

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“…However, it is important to note that low excretion rate from human body does not necessarily lead to their detection in low concentration or frequency in water. For instance, excretion rate of CBZ and a few other PhACs such as ibuprofen, clofibric acid and gemfibrozil is generally low (1-10%), while excretion rates of up to 70% were reported for some PhACs such as atenolol and paracetamol [76,77]. However, as noted above, CBZ is detected in significantly high concentration in raw and treated wastewater because of its low removal by the natural attenuation process and by the WWTPs [4,78].…”

Section: Wastewater Treatment Plant Effluentmentioning

confidence: 98%

Carbamazepine as a Possible Anthropogenic Marker in Water: Occurrences, Toxicological Effects, Regulations and Removal by Wastewater Treatment Technologies

Hai

Yang

Asif

et al. 2018

Water

146

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Carbamazepine (CBZ), a pharmaceutical compound, has been proposed as an anthropogenic marker to assess water quality due to its persistence in conventional treatment plants and widespread presence in water bodies. This paper presents a comprehensive literature review on sources and occurrences of CBZ in water bodies, as well as toxicological effects and regulations of the drug. Given the documented side effects of CBZ on the human body when taken medicinally, its careful monitoring in water is recommended. CBZ residues in drinking water may provide a pathway to embryos and infants via intrauterine exposure or breast-feeding, which may cause congenital malformations and/or neurodevelopmental problems over long term exposure. An in-depth technical assessment of the conventional and advanced treatment technologies revealed the inadequacy of the standalone technologies. Compared to conventional activated sludge and membrane bioreactor processes, effective removal of CBZ can be achieved by nanofiltration and reverse osmosis membranes. However, recent studies have revealed that harsh chemical cleaning, as required to mitigate membrane fouling, can often reduce the long-term removal efficiency. Furthermore, despite the efficient performance of activated carbon adsorption and advanced oxidation processes, a few challenges such as cost of chemicals and regeneration of activated carbon need to be carefully considered. The limitations of the individual technologies point to the advantages of combined and hybrid systems, namely, membrane bioreactor coupled with nanofiltration, adsorption or advanced oxidation process.

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Section: Wastewater Treatment Plant Effluentmentioning

confidence: 98%

Carbamazepine as a Possible Anthropogenic Marker in Water: Occurrences, Toxicological Effects, Regulations and Removal by Wastewater Treatment Technologies

Hai

Yang

Asif

et al. 2018

Water

146

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“…However, we detected NA4AP not only in urine samples after occupational exposure to aniline, but also in each sample from individuals without occupational exposure to aniline. While for some individuals the use of analgesics (acetaminophen/paracetamol) could explain high urinary NA4AP levels, for many other individuals with high NA4AP levels, we could rule out recent intake of the pharmaceutical by questionnaire (Modick et al 2013(Modick et al , 2014Nielsen et al 2015). We suggested exposure to aniline to be one possible origin of the internal burden to NA4AP.…”

Section: Introductionmentioning

confidence: 94%

“…Formic acid was obtained from MERCK (Darmstadt, Germany). Finally, N-acetyl-4-aminophenol-d 3 and acetanilide-d 3 were synthesized by selective acetylation of 4-aminophenol at the amino group and by acetylation of aniline, both with activated acetic acid-d4 as previously described by (Dierkes et al 2014). …”

Section: Chemicalsmentioning

confidence: 99%

“…NA4AP as the major metabolite of aniline was found in the mg/L range in urine samples of employees exposed to aniline air concentrations below 2 ppm (Lewalter and Korallus 1985;Deutsche Forschungsgemeinschaft 1993). In recent studies from our group with volunteers exposed to (airborne) aniline, we also quantified urinary NA4AP in the mg/L range (Dierkes et al 2014;Modick et al 2014). However, we detected NA4AP not only in urine samples after occupational exposure to aniline, but also in each sample from individuals without occupational exposure to aniline.…”

Section: Introductionmentioning

confidence: 99%

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Human metabolism and excretion kinetics of aniline after a single oral dose

et al. 2015

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Aniline is an important source material in the chemical industry (e.g., rubber, pesticides, and pharmaceuticals). The general population is known to be ubiquitously exposed to aniline. Thus, assessment of aniline exposure is of both occupational and environmental relevance. Knowledge on human metabolism of aniline is scarce. We orally dosed four healthy male volunteers (two fast and two slow acetylators) with 5 mg isotope-labeled aniline, consecutively collected all urine samples over a period of 2 days, and investigated the renal excretion of aniline and its metabolites by LS-MS/MS and GC-MS. After enzymatic hydrolysis of glucuronide and sulfate conjugates, N-acetyl-4-aminophenol was the predominant urinary aniline metabolite representing 55.7-68.9 % of the oral dose, followed by the mercapturic acid conjugate of N-acetyl-4-aminophenol accounting for 2.5-6.1 %. Acetanilide and free aniline were found only in minor amounts accounting for 0.14-0.36 % of the dose. Overall, these four biomarkers excreted in urine over 48 h post-dose represented 62.4-72.1 % of the oral aniline dose. Elimination half-times were 3.4-4.3 h for N-acetyl-4-aminophenol, 4.1-5.5 h for the mercapturic acid conjugate, and 1.3-1.6 and 0.6-1.2 h for acetanilide and free aniline, respectively. Urinary maximum concentrations of N-acetyl-4-aminophenol were reached after about 4 h and maximum concentrations of the mercapturic acid conjugate after about 6 h, whereas concentrations of acetanilide and free aniline peaked after about 1 h. The present study is one of the first to provide reliable urinary excretion factors for aniline and its metabolites in humans after oral dosage, including data on the predominant urinary metabolite N-acetyl-4-aminophenol, also known as an analgesic under the name paracetamol/acetaminophen.

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“…Comprehensive new data on human exposures to a range of mainly non-persistent chemicals present in our daily environment are also presented (Frederiksen et al 2014) including a study showing that aniline, to which whole populations are exposed, is a hitherto overlooked source of exposure to paracetamol -a pharmaceutical compound -recently shown to affect the production of testosterone (see Modick et al (2014) …”

mentioning

confidence: 99%