Secular trends of urinary phthalate metabolites in 7-year old children and association with building characteristics: Hokkaido study on environment and children's health.

The widespread commercial production and use of phthalates as plasticizers in consumer products have led to significant human exposure. Some phthalates are known to disrupt the endocrine system and result in adverse health outcomes. As such, they have been regulated in materials used for children's items and food packages. In this study, we examined the secular trend of urinary phthalate metabolites in children and the association between metabolites and building characteristics. In total, 400 first-morning spot urine samples of 7 years old children collected from 2012 to 2017 from an ongoing birth cohort study were examined. Parents provided information on demographics and building questionnaires. We analyzed 10 urinary phthalate metabolites from five phthalate diesters using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS): MiBP, MnBP, MBzP, MEHP, MEOHP, MEHHP, MECPP, MiNP, OH-MiNP, and cx-MiNP. A multivariable regression model with creatinine-corrected metabolite levels was applied to assess secular trends during 2012-2017. The association between metabolite levels and building characteristics was investigated using a mutual-adjusted linear regression. The metabolites MnBP, MEHP, MEOHP, MEHHP, MECPP, and OH-MiNP were detected in all samples. The highest median concentration was for MECPP 37.4 ng/mL, followed by MnBP and MEHHP at concentrations of 36.8 and 25.8 ng/mL, respectively. Overall, DBP, BBzP, and DINP metabolite concentrations in this study were comparable to or lower than those in previous studies from Japan and other countries in a similar study period. Higher concentrations of DEHP metabolites were observed in this study than in children from the USA and Germany, as per previous reports. Despite updated phthalate regulations and reports of production volume change in Japan, all the measured metabolites showed a stable trend between 2012 and 2017. Higher phthalate metabolite levels were observed among children from households with low annual income, those who lived in old buildings, and those with window opening habits of ≥1 h than ≤1 h. In contrast, children in houses that vacuumed 4 or more days/week showed a lower level of MnBP than those in houses that vacuumed ≤3 days/week. This study demonstrates that the internal exposure level of phthalates in Japanese children was stable from 2012 to 2017. Our findings suggest that phthalate exposure in children is consistent. Thus, improvements in the indoor environment, such as frequent vacuuming, may reduce exposure. Biomonitoring of phthalates is critical for elucidating their possible health effects and developing mitigation strategies.