Di-iso-nonylphthalate (DINP) metabolites in human urine after a single oral dose of deuterium-labelled DINP

Abstract

Di-iso-nonylphthalate (DINP), a complex mixture of predominantly nine-carbon branched chain dialkyl phthalate isomers, has replaced di-(2-ethylhexyl)phthalate (DEHP) as the major plasticiser for polyvinylchloride (PVC) polymers. Similar to DEHP, DINP is a developmental and reproductive toxicant in rodents. This study for the first time describes human metabolism and elimination of DINP in a male volunteer after we applied a single oral DINP dose of 1.27 mg/kg body-weight. To avoid interference by omnipresent background exposure we used deuterium-labelled DINP. We investigated the urinary excretion of the simple monoester mono-iso-nonylphthalate (MINP) and oxidised isomers with hydroxy (OH-MINP), oxo (oxo-MINP) and carboxy (carboxy-MINP) functional groups. We used isomeric MINP and three specific oxidised isomer standards for quantification: mono-(4-methyl-7-hydroxy-octyl)phthalate (7OH-MMeOP), mono-(4-methyl-7-oxo-octyl)phthalate (7oxo-MMeOP) and mono-(4-methyl-7-carboxyheptyl)phthalate (7carboxy-MMeHP). These specific DINP metabolites are currently the only synthetic DINP metabolite standards available. Within 48 h we recovered 43.6% of the applied dose in urine as the above DINP metabolites, 20.2% as OH-MINP, 10.7% as carboxy-MINP, 10.6% as oxo-MINP and only 2.2% as MINP. Other oxidised DINP metabolites not determined in this study probably increase the share of the DINP dose excreted via urine. Elimination followed a multi-phase pattern, elimiation half-lives in the second phase (beginning 24 h post-dose) can only roughly be estimated to be 12 h for the OH- and oxo-MINP-metabolites and 18 h for carboxy-MINP metabolites. After 24 h, the carboxy-MINP metabolites replaced the OH-MINP metabolites as the major urinary metabolites. All oxidised DINP metabolites are suitable parameters for biomonitoring human DINP exposure.