Quantitative investigation of the urinary excretion of three specific monoester metabolites of the plasticizer diisononyl adipate (DINA)

Authors

  • Alexandra Gotthardt Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany https://orcid.org/0000-0002-7258-6579
  • Daniel Bury Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany https://orcid.org/0000-0003-1283-3133
  • Hans-Willi Kling University of Wuppertal, Department of Chemistry and Biology, Gaußstraße 20, 42119 Wuppertal, Germany
  • Rainer Otter BASF SE, Industrial Petrochemicals Europe; E-CPI/R-H202, Carl-Bosch-Straße 38, 67056 Ludwigshafen, Germany https://orcid.org/0000-0002-9515-5384
  • Tobias Weiss Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany https://orcid.org/0000-0003-1056-5614
  • Thomas Brüning Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany https://orcid.org/0000-0001-9560-5464
  • Holger M. Koch Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany, Tel.: +49 (0)30 13001 4415, Fax: +49 (0)30 13001 864415, E-mail: koch@ipa-dguv.de https://orcid.org/0000-0002-8328-2837

DOI:

https://doi.org/10.17179/excli2021-3360

Keywords:

diisononyl adipate, DINA, plasticizer, metabolism, oral dose, human biomonitoring

Abstract

Diisononyl adipate (DINA) is a plasticizer used in PVC products as an alternative for restricted phthalate plasticizers. With this study, we provide first data on human DINA metabolism and excretion. We postulated mono(hydroxy-isononyl) adipate (OH-MINA), mono(oxo-isononyl) adipate (oxo-MINA), and mono(carboxy-isooctyl) adipate (cx-MIOA) as specific DINA metabolites based on the known human metabolism of structurally similar adipates and phthalates. Urinary excretion was quantitatively investigated after a single oral dose (113 to 145 µg/kg body weight) to three healthy volunteers using a newly developed online-SPE-LC-MS/MS method with isotope dilution and LOQs between 0.3 – 0.6 µg/L. OH-MINA turned out to be the major of the three metabolites with consistent urinary excretion fractions (FUEs) of 0.020-0.023 % among all volunteers. Oxo-MINA and cx-MIOA were excreted with lower shares (mean: 0.003 % and 0.009 %, respectively). For all three metabolites, urinary concentrations peaked quickly between 1.4 and 2.3 h post dose with maximum concentrations of 23.1 (OH-MINA), 2.87 (oxo-MINA) and 9.83 µg/L (cx-MIOA). Thus, FUEs and urinary concentrations were rather low for these specific metabolites, with the major share of the dose presumably being excreted as non-specific metabolites such as adipic acid. In a pilot population (n=35) of German adults without known DINA exposure, we could not detect any of the three metabolites, contrary to the dosage study, indicating to population exposures lower than 50 µg/kg body weight/day. The new HBM method in conjunction with the new FUEs can be used for objective DINA exposure and risk assessment especially in populations with potentially higher DINA exposures.

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Published

2021-02-19

How to Cite

Gotthardt, A., Bury, D., Kling, H.-W., Otter, R., Weiss, T., Brüning, T., & Koch, H. M. (2021). Quantitative investigation of the urinary excretion of three specific monoester metabolites of the plasticizer diisononyl adipate (DINA). EXCLI Journal, 20, 412–425. https://doi.org/10.17179/excli2021-3360

Issue

Vol. 20 (2021)

Section

Original articles

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Copyright (c) 2021 Alexandra Gotthardt, Daniel Bury, Hans-Willi Kling, Rainer Otter, Tobias Weiss, Thomas Brüning, Holger M. Koch

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