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Phthalates are widely used in consumer products and are well-known for adverse endocrine outcomes. Di-(2-ethylhexyl) phthalate (DEHP), one of the most extensively used phthalates, has been rapidly substituted with alternative plasticizers in many consumer products. The aim of this study was to assess urinary phthalate and alternative plasticizer exposure and associated risks in children of three Asian countries with different geographical, climate, and cultural characteristics. Children were recruited from elementary schools of Saudi Arabia (n = 109), Thailand (n = 104), and Indonesia (n = 89) in 2017–2018, and their urine samples were collected. Metabolites of major phthalates and alternative plasticizers were measured in the urine samples by HPLC-MS/MS. Urinary metabolite levels differed substantially between the three countries. Metabolite levels of diisononyl phthalate (DiNP), diisodecyl phthalate (DiDP), di­(2-ethylhexyl) terephthalate (DEHTP), and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) were the highest in Saudi children: Median urinary concentrations of oxo-MiNP, OH-MiDP, 5cx-MEPTP, and OH-MINCH were 8.3, 8.4, 128.0, and 2.9 ng/mL, respectively. Urinary DEHP metabolite concentrations were the highest in the Indonesian children. The hazard index (HI) derived for the plasticizers with antiandrogenicity based reference doses (RfDAA) was >1 in 86%, 80%, and 49% of the Saudi, Indonesian, and Thai children, respectively. DEHP was identified as a common major risk driver for the children of all three countries, followed by DnBP and DiBP depending on the country. Among alternative plasticizers, urinary DEHTP metabolites were detected at levels comparable to those of DEHP metabolites or higher among the Saudi children, and about 4% of the Saudi children exceeded the health based human biomonitoring (HBM)-I value. Priority plasticizers that were identified among the children of three countries warrant refined exposure assessment for source identification and relevant exposure reduction measures.

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Nonylphenol (NP) is an endocrine-disrupting anthropogenic chemical that is ubiquitous in the environment. Human biomonitoring data and knowledge on internal NP exposure are still sparse, and its human metabolism is largely unknown. Therefore, in this study, we investigated human metabolism and urinary excretion of NP. Three male volunteers received a single oral dose of 1 mg 13 C 6 -labeled NP (10.6−11.7 μg/kg body weight). Consecutive full urine voids were collected for 48 h. A metabolite screening identified nine ring-and/or side chain-oxidized metabolites. We chose the most promising hits, the alkyl chainoxidized metabolites hydroxy-NP (OH-NP) and oxo-NP, for quantitative investigation next to the parent NP. For this purpose, we newly synthesized specific n − 1-oxidized monoisomeric analytical standards. Quantification of the polyisomeric metabolites was performed via online-solid phase extraction-LC-MS/MS with stable isotope dilution using a previously published consensus method. Alkyl chain hydroxylation (OH-NP) constituted the major metabolism pathway representing 43.7 or 62.2% (depending on the mass transition used for quantification) of the NP dose excreted in urine. The urinary excretion fraction (F UE ) for oxo-NP was 6.0 or 9.3%. The parent NP, quantified via an analogous isomeric 13 C 6 -NP standard, represented 6.6%. All target analytes were excreted predominately as glucuronic acid conjugates. Excretion was rather quick, with concentration maxima in urine 2.3−3.4 h after dosing and biphasic elimination kinetics (elimination half-times first phase: 1.0−1.5 h and second phase: 5.2−6.8 h). Due to its high F UE and insusceptibility to external contamination (contrary to parent NP), OH-NP represents a robust and sensitive novel exposure biomarker for NP. The novel F UE s enable to robustly back-calculate the overall NP intakes from urinary metabolite levels in population samples for a well-informed cumulative exposure and risk assessment.