Urinary metabolite excretion after oral dosage of bis(2-propylheptyl)phthalate (dphp) to five male volunteers - characterization of suitable biomarkers for human biomonitoring
Leng, G; Koch, HM; Gries, W; Schütze, A; Langsch, A; Brüning, T; Otter, R
HERO ID
2345945
Reference Type
Journal Article
Year
2014
Language
English
PMID
| HERO ID | 2345945 |
|---|---|
| In Press | No |
| Year | 2014 |
| Title | Urinary metabolite excretion after oral dosage of bis(2-propylheptyl)phthalate (dphp) to five male volunteers - characterization of suitable biomarkers for human biomonitoring |
| Authors | Leng, G; Koch, HM; Gries, W; Schütze, A; Langsch, A; Brüning, T; Otter, R |
| Journal | Toxicology Letters |
| Volume | 231 |
| Issue | 2 |
| Page Numbers | 282-288 |
| Abstract | Di(2-propylheptyl) phthalate (DPHP), a high molecular weight phthalate, is primarily used as a plasticizer in polyvinylchloride and vinyl chloride copolymers for technical applications, as a substitute for other phthalates currently being scrutinized because of endocrine disrupting effects. We determined urinary excretion fractions of three specific DPHP metabolites (mono-2-(propyl-6-hydroxy-heptyl)-phthalate (OH-MPHP), mono-2-(propyl-6-oxoheptyl)-phthalate (oxo-MPHP) and mono-2-(propyl-6-carboxy-hexyl)-phthalate (cx-MPHxP)) after oral dosing of five volunteers with 50mg labelled DPHP-d4 and subsequent urine sampling for 48h. These excretion fractions are used to back calculate external intakes from metabolite measurements in spot urine analysis. Following enzymatic hydrolysis to cleave possible conjugates, we determined these urinary metabolites by HPLC-NESI-MS/MS with limits of quantification (LOQ) between 0.3-0.5μg/l. Maximum urinary concentrations were reached within 3-4hrs post dose for all three metabolites; elimination half-lives were between 6 to 8hrs. We identified oxo-MPHP as the major oxidized metabolite in urine representing 13.5±4.0% of the DPHP dose as the mean of the five volunteers within 48hrs post dose. 10.7±3.6% of the dose was excreted as OH-DPHP and only 0.48±0.13% as cx-MPHxP. Thus, within 48hrs, 24.7±7.6% of the DPHP dose was excreted as these three specific oxidized DPHP metabolites, with the bulk excreted within 24hrs post dose (22.9±7.3%). These secondary, oxidized metabolites are suitable and specific biomarkers to determine DPHP exposure. In population studies, however, chromatographic separation of these metabolites from other isomeric di-isodecyl phthalate (DIDP) metabolites is warranted (preferably by GC-MS) in order to distinguish DPHP from general DIDP exposure. Palatinol®, Hexamoll® and DINCH® are registered trademarks of BASF SE, Germany. |
| Doi | 10.1016/j.toxlet.2014.06.035 |
| Pmid | 24973492 |
| Wosid | WOS:000346174100023 |
| Url | <Go to ISI>://WOS:000346174100023 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Keyword | Biomonitoring; Di(2-propylheptyl)phthalate; DPHP metabolites; Urinary excretion; Human volunteer study; HPLC-NESI-MS/MS |