Biological Monitoring of Aromatic Amines - Metabolism of aniline and elimination kinetics of its metabolites after controlled exposure

摘要

The aromatic amine aniline is an important base material in chemical industry. It is also an integral part of tobacco smoke. In Biological Monitoring exposure to aniline is regularly assessed by measuring urinary aniline after hydrolysis or in form of its covalent haemoglobin adducts. As data on metabolism and elimination kinetics is available from several animal species but lacks from humans we conducted a study under controlled exposure in an exposure chamber (ethics approval 4333-12, Ruhr-Universitaet Bochum). Four non-smoking slow acetylating volunteers (2 m, 2 f) were exposed to 2 ppm aniline for 8 hours. Spot urine specimen were taken prior to exposure and ad libitum up to 26 hours postexposure. In these samples N-acetyl-2-aminophenol, N-acetyl-4-aminophenol and N-acetylaniline were quantified using HPLC-MS/MS and aniline was quantified after acidic hydrolysis using GC-MS/MS. N-acetyl-4-aminophenol was the major urinary metabolite representing 23-54% of the total aniline dose. N-acetyl-4-aminophenol was eliminated into urine with a half-life between 6 and 12 hours. Urinary background concentrations of N-acetyl-2-aminophenol in the mg/L range hampered the evaluation of toxicokinetic data for this proposed phenolic aniline metabolite. The amount of aniline found after hydrolysis essentially originated from N-acetylaniline. N-acetylaniline showed an initial elimination half-life of about 3 hours. N-acetylaniline accounted for less than 0.5% of the dose which is considerably smaller than expected from animal data. If the acetylator phenotype has a significant impact on metabolite ratios or elimination velocity in humans will be studied in further experiments. The sources of the N-acetyl-2-aminophenol urinary background concentrations in humans are unknown so far.