Metabolism of the plasticizer and phthalate substitute diisononyl-cyclohexane-1,2-dicarboxylate (DINCH®) in humans after single oral doses
Hexamoll® DINCH® (diisononyl-cyclohexane-1,2-dicarboxylate) is a new high-molecular-weight plasticizer and a phthalate substitute. In this study, the metabolism of DINCH® was investigated by oral dosage of three male volunteers with approximately 50 mg Hexamoll® DINCH® (resulting in individual doses between 0.552 and 0.606 mg/kg body weight). Their urine samples were consecutively collected over 48 h. In analogy to di-iso-nonylphthalate (DINP) metabolism, we quantified the simple monoester mono-isononyl-cyclohexane-1,2-dicarboxylate (MINCH) and its secondary oxidized metabolites with HPLC–MS/MS via isotope dilution analysis. Additionally, we quantified the unspecific full breakdown product, cyclohexane-1,2-dicarboxylic acid (CHDA), via standard addition. All postulated metabolites were present in all samples analyzed. The unspecific CHDA was identified as the major urinary metabolite representing 23.7 % of the dose as the mean of the three volunteers (range 20.0–26.5 %). 14.8 % (11.3–16.7 %) of the dose was excreted as monoesters with oxidative modifications, in particular OH-MINCH 10.7 % (7.7–12.9 %), oxo-MINCH 2.0 % (1.5–2.6 %) and carboxy-MINCH 2.0 % (1.8–2.3 %). Less than 1 % was excreted as the simple monoester MINCH. In sum, 39.2 % (35.9–42.4 %) of the DINCH® dose was excreted as these metabolites in urine within 48 h. Over 90 % of the metabolites investigated were excreted within 24 h after application. The secondary oxidized metabolites, with elimination half-times between 10 and 18 h, proved to be apt and specific biomarkers to determine DINCH® exposure. With this study, we provide reliable urinary excretion factors to calculate DINCH® intakes based on these metabolites in environmental and occupational studies.
KeywordsDINCH Phthalate substitute Human metabolism Urinary metabolites Excretion fractions Human biomonitoring
The study was performed under the framework of the cooperation project of the German Federal Environment Ministry (BMU) and German Chemicals Industry Association (VCI) on human biomonitoring in order to improve the knowledge of substances taken up by the human organism. The metabolism study and method development were financed by the Chemie Wirtschaftsförderungsgesellschaft mbH. We would like to thank Dr. Rainer Otter, BASF SE, for excellent support within the project.
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