Oxo-MPHP is the most abundant metabolite, representing in the mean over the five volunteers 13.5% of the oral DPHP

dose in urine after 48 h, closely followed by OH-MPHP (10.7%). Cx-MPHxP (0.5%) is regarded as a minor metabolite. All three oxidized metabolites represent about 25% of the dose excreted in urine within 48 h. Wittassek and Angerer (2008) reported the first results on human DPHP metabolism, when the senior author ingested a single DPHP dose of 98 mg during breakfast. In their pilot study they reported that after 61 h around 34% of the applied dose was excreted with urine as oxidized metabolites (including approx. 1% as the simple monoester). Taking into account that they included other metabolites with oxidative modifications and that their sampling time was longer, their data are consistent with the data of the study reported Ibrutinib solubility dmso here. The data obtained for DPHP in this study is also consistent with human metabolism data for other high molecular weight

phthalates like DEHP and DINP (Koch et al., 2005, Koch et al., 2007, Anderson et al., 2011 and Kessler et al., 2012). Similar elimination half-lives were also calculated for all DPHP metabolites (6.51–8.16 h) compared with DEHP and DINP. They are in good accordance to the respective metabolite half-lives of DINP (4–8 h; Anderson et al., 2011) and DEHP (4.6–6.6 h; Kessler et al., 2012). For DEHP, the three main, oxidized metabolites KU-57788 excreted in urine represent about 38.6–57.8% of the oral dose, depending on the study; for DINP, the three main oxidized metabolites excreted in urine represent about 29.8–37.5% of the dose, depending on the study. In all these studies, it was shown that an increasing

alkyl chain length of the plasticizer results in a decreased formation of the simple monoester. Thus, for high molecular weight plasticizers, the simple monoester is not a relevant urinary metabolite. Furthermore, since the simple monoester is prone to external contamination, mafosfamide the oxidized metabolites have to be regarded as the most suitable biomarkers for monitoring exposure to high molecular weight phthalates in urine (Koch and Calafat, 2009). The metabolic conversion factors established in this study for DPHP based on the five male volunteers allow a reliable back calculation from urinary DPHP metabolite levels to external exposure, and thus enable a solid risk assessment of the human body burden for the general public as well as for individuals occupationally exposed. A reliable back-calculation to DPHP exposure, however, can only be performed, if the above secondary, oxidized DPHP metabolites are chromatographically separated from the oxidized metabolites of DIDP/DINP that are generally present in urine samples of the general population, due to the omnipresent DIDP/DINP exposures. Gries et al.