Search

Nonylphenol (NP) is an endocrine-disrupting anthropogenic chemical that is ubiquitous in the environment. Human biomonitoring data and knowledge on internal NP exposure are still sparse, and its human metabolism is largely unknown. Therefore, in this study, we investigated human metabolism and urinary excretion of NP. Three male volunteers received a single oral dose of 1 mg 13C6-labeled NP (10.6–11.7 μg/kg body weight). Consecutive full urine voids were collected for 48 h. A metabolite screening identified nine ring- and/or side chain-oxidized metabolites. We chose the most promising hits, the alkyl chain-oxidized metabolites hydroxy-NP (OH-NP) and oxo-NP, for quantitative investigation next to the parent NP. For this purpose, we newly synthesized specific n– 1-oxidized monoisomeric analytical standards. Quantification of the polyisomeric metabolites was performed via online-solid phase extraction-LC-MS/MS with stable isotope dilution using a previously published consensus method. Alkyl chain hydroxylation (OH-NP) constituted the major metabolism pathway representing 43.7 or 62.2% (depending on the mass transition used for quantification) of the NP dose excreted in urine. The urinary excretion fraction (FUE) for oxo-NP was 6.0 or 9.3%. The parent NP, quantified via an analogous isomeric 13C6-NP standard, represented 6.6%. All target analytes were excreted predominately as glucuronic acid conjugates. Excretion was rather quick, with concentration maxima in urine 2.3–3.4 h after dosing and biphasic elimination kinetics (elimination half-times first phase: 1.0–1.5 h and second phase: 5.2–6.8 h). Due to its high FUEand insusceptibility to external contamination (contrary to parent NP), OH-NP represents a robust and sensitive novel exposure biomarker for NP. The novel FUEs enable to robustly back-calculate the overall NP intakes from urinary metabolite levels in population samples for a well-informed cumulative exposure and risk assessment.

ObjectiveBladder cancer is the fourth most frequent cancer among men in Germany. Aromatic amines can cause bladder cancer and therefore cancerogenic aromatic amines have been banned a long time ago from workplace, but a long latency can still increase the risk of former exposed workers. In this study, we will assess the risk of bladder cancer in a cohort of chemical workers with earlier use of aromatic amines compared to the general population.MethodsIn the prospective cohort study UroScreen, 1800 former chemical workers exposed to aromatic amines were offered to participate in an early detection of bladder cancer by means of tumour markers. In 2003–10, 1609 people were examined at least once. The exposure to aromatic amines was determined by means of questionnaires. The observed bladder cancer incidence was compared with the expected incidence in the general population. Bladder cancer risk was estimated as standardised incidence ratio.ResultsNine incidence urinary bladder carcinoma occurred during the study. Eight cases were ex-smokers and one case was non-smoker. All cases were exposed for at least 10 years, including six cases longer than 20 years. Compared to the general population, the risk of bladder cancer was 2.94 (95% CI 1.35–5.59).ConclusionsSince almost all cases have both smoked and were highly exposed, reliable risk detection is difficult. Nevertheless, in view of a threefold increased risk, the early detection of urinary bladder carcinomas were promising.