New reference value and the background exposure for the PAH metabolites 1-hydroxypyrene and 1- and 2-naphthol in urine of the general population in Germany: Basis for validation of human biomonitoring data in environmental medicine

N-acetyl-4-aminophenol (acetaminophen/paracetamol, NA4AP) is one of the most commonly used over-the-counter analgesic and antipyretic drugs. Recent studies have reported anti-androgenic effects of NA4AP in vitro and possible associations between intrauterine exposure to NA4AP and the development of male reproductive disorders in humans. NA4AP is also a major metabolite of aniline (phenylamine), representing 75–86% of the aniline dose excreted in urine. Aniline is an important large-volume intermediate in several industrial processes. Besides individuals in various occupational settings with aniline exposure, the general population is also known to be ubiquitously exposed to aniline. In this article, we provide an overview of the recent literature concerning the intake of NA4AP during pregnancy and the possible anti-androgenic effects of NA4AP as well as literature concerning its known metabolic precursor aniline. We also present new research data, including the first human biomonitoring data on NA4AP excretion in urine, showing ubiquitous NA4AP body burdens in the general population at a wide range of concentrations. We found a small but significant impact of smoking on urinary NA4AP concentrations. We further present preliminary data on NA4AP excretion after therapeutic acetaminophen use, after aniline exposure in an occupational setting, and during a controlled fasting study (excluding oral exposure to both aniline and acetaminophen). Our findings indicate exposure to aniline (or aniline-releasing substances) as well as nutrition (next to the direct use of acetaminophen as medication) as possible sources of internal body burdens of NA4AP.

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Carbonic Anhydrase Sensitivity to Pesticides: Perspectives for Biomarker Development

International Journal of Molecular Sciences ◽

10.3390/ijms21103562 ◽

2020 ◽

Vol 21 (10) ◽

pp. 3562

Author(s):

Maria Giulia Lionetto ◽

Roberto Caricato ◽

Maria Elena Giordano

Keyword(s):

Carbonic Anhydrase ◽

Environmental Medicine ◽

Environmental Monitoring ◽

Pesticide Exposure ◽

Human Biomonitoring ◽

Target Species ◽

Physiological Processes ◽

Occupational And Environmental Medicine

Carbonic anhydrase (CA) is a widespread metalloenzyme playing a pivotal role in several physiological processes. Many studies have demonstrated the in vitro and in vivo sensitivity of CA to the exposure to several classes of pesticides in both humans and wildlife. This review aims to analyze and to discuss the literature available in this field, providing a comprehensive view useful to foresee perspectives for the development of novel CA-based pesticide biomarkers. The analysis of the available data highlighted the ability of several pesticide molecules to interact directly with the enzyme in humans and wildlife and to inhibit CA activity in vitro and in vivo, with possible alterations of key physiological functions. The analysis disclosed key areas of further research and, at the same time, identified some perspectives for the development of novel CA-based sensitive biomarkers to pesticide exposure, suitable to be used in several fields from human biomonitoring in occupational and environmental medicine to environmental monitoring on non-target species.

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