German Environmental Specimen Bank: Urine Samples from 1999-2017 Document Rapid Increase in Exposure to the Para-Phthalate Plasticizer DEHTP

Abstract

Di(2-ethylhexyl) terephthalate (DEHTP) is increasingly used as an alternative to reprotoxic ortho-phthalate plasticizers, e.g. di(2-ethylhexyl) phthalate (DEHP), in everyday products such as food contact materials, toys and medical devices. In Western Europe, DEHTP consumption rose from 2,000 t in 2002, to 100,000 t in 2014 and a predicted 135,000 t in 2019.To investigate for possible increases of DEHTP exposure in the German population over time, we analyzed 600 24-hour urine samples of the German Environmental Specimen Bank for specific DEHTP metabolites as exposure biomarkers. Samples were collected in the years 1999-2017 (ten sampling years, 30 male and 30 female volunteers each, aged 20-29). The samples were blinded and randomized before analysis. Four urinary DEHTP metabolites (side-chain oxidized monoesters) were determined by online SPE LC-MS/MS with isotope dilution quantification. The limits of quantification were 0.2 µg/L (5cx-MEPTP and 5oxo-MEHTP), 0.3 µg/L (5OH-MEHTP) and 0.4 µg/L (2cx-MMHTP).From 1999 until 2009 the main oxidized DEHTP metabolite 5cx-MEPTP was rarely detected. Afterwards, detection rates increased significantly (8% in 2009, 42% in 2011, 95% in 2013, 98% in 2015, and 100% in 2017). The median concentration for 5cx-MEPTP increased from <LOQ in 1999 to 3.35 µg/L in 2017. Detection rates and concentrations for the other metabolites were lower, as expected from human metabolism studies, but strongly correlated with 5cx-MEPTP. Overall, urinary 5cx-MEPTP concentrations were well below the health based guidance value (HBM-I) of 2800 µg/L, and calculated daily intakes were well below the tolerable daily intake of 1 mg/kg bw*d.For the first time, we document the increasing exposure to DEHTP of the German population in a robust set of 600 24-hour urine samples collected between 1999 and 2017. Although considered uncritical for now, the steep increase in DEHTP exposure calls for a continued exposure monitoring.