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

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 metabo...

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Bibliographic Details
Published in:Archives of toxicology 2016-06, Vol.90 (6), p.1325-1333
Main Authors: Modick, Hendrik, Weiss, Tobias, Dierkes, Georg, Koslitz, Stephan, Käfferlein, Heiko Udo, Brüning, Thomas, Koch, Holger Martin
Format: Article
Language:English
Subjects:
Administration, Oral
Adult
Aniline Compounds - metabolism
Aniline Compounds - toxicity
Aniline Compounds - urine
Biomarkers
Biomedical and Life Sciences
Biomedicine
Biotransformation
Chromatography, High Pressure Liquid
Dose-Response Relationship, Drug
Environmental Exposure - analysis
Environmental Health
Environmental Pollutants - metabolism
Environmental Pollutants - toxicity
Environmental Pollutants - urine
Gas Chromatography-Mass Spectrometry
Healthy Volunteers
Human exposure
Humans
Kinetics
Male
Metabolic Clearance Rate
Metabolism
Occupational Medicine/Industrial Medicine
Organic chemicals
Pharmacology/Toxicology
Tandem Mass Spectrometry
Toxicokinetics
Toxicokinetics and Metabolism
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Summary: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.
ISSN:0340-5761
1432-0738
DOI:10.1007/s00204-015-1566-x