Quantitative Measurement of Phthalate Exposure Biomarker Levels in Diaper-Extracted Urine of Japanese Toddlers and Cumulative Risk Assessment: An Adjunct Study of JECS Birth Cohort

Phthalate exposure monitoring and risk assessment in non-toilet-trained children are rarely reported. This adjunct study of the Japan Environment and Children's Study assessed cumulative health risks in 1.5-year-old toddlers in the Aichi regional subcohort by biomonitoring 16 urinary metabolites of eight phthalate plasticizers. Overnight urine was extracted from toddlers' diapers (n = 1077), and metabolites were quantified using ultraperformance liquid chromatography coupled with tandem mass spectrometry. The analyses' quality was assured by running quality control samples. The highest geometric mean concentration was found for mono-(2-ethyl-5-carboxypentyl) phthalate, followed by mono-isobutyl phthalate (23 and 21 μg/L, respectively). Di-2-ethylhexyl phthalate (DEHP) and di-butyl phthalate exhibited higher risks [hazard quotient (HQ) > 1] than the cutoff level in a small proportion of toddlers; 8 and 14% of toddlers were at cumulative risk of multiple phthalates beyond the cutoff level [hazard index, (HI) > 1], based on the tolerable daily intake of the European Food Safety Authority and the United States Environmental Protection Agency Reference Dose. HI > 1 for antiandrogenicity in creatinine-unadjusted and -adjusted estimations were exhibited by 36 and 23% of the children, respectively. Thus, identifying exposure sources and mitigating exposure are necessary for risk management. Additionally, continuous exposure assessment and evaluation of health outcomes, especially antiandrogenic effects, are warranted.