Human-Biomonitoring of N-acetyl-4-aminophenof (paracetamol/acetaminophen) - the major metabolite of aniline

摘要

Aniline is an important building-block in several industrial processes (e.g. rubber, colorants, pesticides and Pharmaceuticals). Exposure to aniline is therefore both of occupational and environmental relevance and the general population is known to be ubiquitously exposed to aniline. N-acetyl-4-aminophenol (NAAP) is the major urinary metabolite of aniline representing 56%-76% of the dose. Furthermore, NAAP, also known under the trade names acetaminophen/paracetamol, is one of the most commonly used over-the-counter analgesics. Recent epidemiological studies suggest that intrauterine exposure to NAAP is a risk factor for the development of male reproductive disorders. Human biomonitoring data on the body burden of the general population (and potentially exposed subpopulations) to NAAP is literally nonexistent. To determine the internal NAAP exposure of the general population, workers exposed to aniline and users of acetaminophen, we developed a fast on-line HPLC-MS/MS-method with isotope dilution quantification of NAAP in urine with a limit of quantification (LOQ) of 0.75 μg/L. In a pilot study, urine samples of 21 volunteers, not occupationally exposed to aniline, were analyzed for NAAP. NAAP was detected in all samples in a wide concentration range between 8.7 μg/L and 22100 μg/L (median 85.7 μg/L). The highest concentration was measured in a volunteer who took acetaminophen approximately a day ago. Half of the volunteers quoted to either never have taken acetaminophen or not during the several weeks before sampling. Therefore, other routes of exposure than direct use of acetaminophen, like aniline exposure or acetaminophen contaminated foodstuff, leading to the NAAP excretions have to be taken into account.