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

  • Toxicokinetics and Metabolism
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Abstract

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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Authors and Affiliations

  1. Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany

    Hendrik Modick, Tobias Weiss, Georg Dierkes, Stephan Koslitz, Heiko Udo Käfferlein, Thomas Brüning & Holger Martin Koch

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  1. Hendrik Modick
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  2. Tobias Weiss
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  3. Georg Dierkes
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  4. Stephan Koslitz
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  5. Heiko Udo Käfferlein
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  6. Thomas Brüning
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  7. Holger Martin Koch
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Correspondence to Holger Martin Koch.

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The authors declare that they have no conflict of interest. The present work was completely financed by the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance Institute of the Ruhr-Universität Bochum (IPA).

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Modick, H., Weiss, T., Dierkes, G. et al. Human metabolism and excretion kinetics of aniline after a single oral dose. Arch Toxicol 90, 1325–1333 (2016). https://doi.org/10.1007/s00204-015-1566-x

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  • DOI: https://doi.org/10.1007/s00204-015-1566-x

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