Identification of Urinary Human Biomarkers of the UV-filter Octyl Methoxycinnamate After Oral Dosage

摘要

Octyl methoxycinnamate (Octinoxate, OMC) is widely used as a UV-filter in personal care products (e.g. lipsticks, sunscreen lotions, night-creams, etc.) in concentrations of up to 10% in the European Union. Due to exposure of the general population, OMC was selected as a substance of interest by the cooperation project between the German Federal Ministry for Environment (BMU) and the German Chemical Industry Association (VCI), which has the aim to provide biomarker based exposure data for fifty emerging substances of concern. We investigated metabolism and urinary excretion of OMC after oral dosage to human volunteers. We collected all consecutive urine samples by their full volume over a period of 48 hours post dose. Potential urinary metabolites were determined via online LC-MS/MS using custom synthesized standard substances or characteristic fragmentation patterns. We identified several specific metabolites of OMC (and de-methylated OMC) with oxidative modifications (hydroxy, oxo and carboxy) at its alkyl side chain. However, these metabolites represented only a minor share of the applied dose in urine (less than 0.1 %). Instead, we identified p-methoxy hippuric acid (PMHA) as a major metabolite of OMC in urine representing approx. 40% of the applied dose. PMHA is a multi-step breakdown metabolite of OMC and we are currently investigating its specificity as biomarker for OMC. We also detected p-methoxy cinnamic acid (PMCA), a precursor of PMHA, albeit at considerably lower concentrations than PMHA itself. The major share of all the above metabolites was excreted within the first 24 hours post dose. Currently we are searching for additional, specific urinary OMC metabolites. With this study we will provide first data on human OMC metabolism and a set of urinary OMC metabolites to be used as biomarkers in future biomonitoring studies for exposure and risk assessment.