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

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.

Potential Health Risk of Endocrine Disruptors in Construction Sector and Plastics Industry: A New Paradigm in Occupational Health

“…Aniline is used in shellacs for wood coloring; thus, construction painters and finishing workers are potentially exposed. Aniline is metabolized in paracetamol, which is an antiandrogen substance [ 36 , 37 ], causing hormonal disturbances [ 99 ].…”

“…In this short communication, the construction and plastics industries were selected as examples of two sectors, in which many workers across Europe are exposed to EDs. These include phthalates, bisphenols, aniline, cadmium and chromium [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ].…”

Acetaminophen Metabolism Revisited Using Non-Targeted Analyses: Implications for Human Biomonitoring

“…Targeted analyses of APAP in blood plasma and urine APAP was analyzed using an adapted version of a method previously described (Modick et al, 2013;Modick et al, 2016). Unlabeled APAP (NA4AP) was used for calibration (the mass transition m/z 152  110 was used for quantification and m/z 152  93 was used as qualifier) and APAP-d4 (NA4AP-d4) was used as internal standard (same mass transitions as reported in Modick et al (Modick et al, 2016)). The gradient for the analytical separation was modified, starting at 15% solvent B (acetonitrile containing 0.05% formic acid).…”

Effect of environmental and pharmaceutical exposures on fetal testis development and function: a systematic review of human experimental data

“…Whilst most of circulating paracetamol in humans comes from use of paracetamol-containing medications, an alternative source has also been described. The industrial chemical aniline, which is found in a wide variety of manufactured products, such as rubber, pharmaceuticals, cosmetics and cigarette smoke, is rapidly metabolized to paracetamol inside the body (Modick et al , 2014, 2016). Furthermore, in-vivo studies in which male mice exposed in utero to aniline have shown similar fetal anti-androgenic effects to those described for exposure to paracetamol (Holm et al , 2015).…”