Metabolism and Excretion Kinetics of Aniline in Four Male Volunteers after Oral Dosage

摘要

Aniline is an important high-volume production chemical and extensively used for the manufacture of Pharmaceuticals, pesticides and colors/dyes. Human biomonitoring studies have shown the ubiquitous exposure of the general population to aniline through urinary aniline measurements. Recently, we also reported on the ubiquitous presence of N-acetyl-4-aminophenol which is both, a major metabolite of aniline and a pain reliever known as paracetamol/acetaminophen. Epidemiological studies suggest intrauterine exposure to paracetamol as risk factor for male reproduction disorders and antiandrogenic effects. Thus, exposure to aniline is of interest to both, occupational and environmental medicine. Knowledge on (human) metabolism of aniline is scare. Therefore we dosed four healthy male volunteers with 5 mg of isotope labelled aniline. Urine was collected consecutively for 48 h and elimination kinetics and conversion factors of the major aniline metabolites were recorded. Aniline and its metabolites were determined using HPLC-MS/MS and GC-MS techniques. N-acetyl-4-aminophenol was the major metabolite representing 50-81% of the dose, followed by its mercapturic acid conjugate with 2.8-8.6% of the dose. The sum of free (unconjuagted) aniline and acetanilide accounted for approximately 0.1-0.3% of the aniline dose. Total recovery of all the aforementioned metabolites was 53-85% of trie oral dose. All metabolites were excreted rather fast with elimination half-times between 1.5-4 h except for the mercapturic acid conjugate (7-9 h). In the present study we provide reliable data on the human metabolism of aniline including urinary metabolite conversion factors. We also show analogies in the metabolism of aniline and paracetamol. The knowledge from this study can be used in future human biomonitoring studies for exposure and risk assessment in environmental and occupational settings.