Ketema Rahel Mesfin, Kasper-Sonnenberg Monika, Ait Bamai Yu, Miyashita Chihiro, Koch Holger M, Pälmke Claudia, Kishi Reiko, Ikeda Atsuko
Center for Environmental and Health Sciences, Hokkaido University, North 12, West 7, Sapporo 060-0812, Japan.
Faculty of Health Sciences, Hokkaido University, North 12, West 5, Sapporo 060-0812, Japan.
Environ Sci Technol. 2023 Aug 15;57(32):11926-11936. doi: 10.1021/acs.est.3c03172. Epub 2023 Jul 28.
Phthalates owing to their endocrine-disrupting effects are regulated in certain products, leading to their replacement with substitutions such as di-2-ethylhexyl terephthalate (DEHTP), 1,2-cyclohexane dicarboxylic acid di(isononyl) ester (DINCH), and di(2-ethylhexyl) adipate (DEHA). However, information on human exposure to these substitutes, especially in susceptible subpopulations such as children, is limited. Thus, we examined the levels and exposure trends of DEHTP, DINCH, and DEHA metabolites in 7 year-old Japanese school children. In total, 180 urine samples collected from 2012 to 2017 were used to quantify 10 DEHTP, DINCH, and DEHA metabolites via isotope dilution liquid chromatography with tandem mass spectrometry. DEHTP and DINCH metabolites were detected in 95.6 and 92.2% of the children, respectively, and DEHA was not detected. This study, annually conducted between 2012 and 2017, revealed a significant ( < 0.05) 5-fold increase in DEHTP metabolites and a 2-fold increase in DINCH metabolites. However, the maximum estimated internal exposures were still below the health-based guidance and toxicological reference values. Exposure levels to DEHTP and DINCH have increased considerably in Japanese school children. DEHA is less relevant. Future studies are warranted to closely monitor the increasing trend in different aged and larger populations and identify the potential health effects and sources contributing to increasing exposure and intervene if necessary.
由于邻苯二甲酸盐具有内分泌干扰作用，某些产品中对其进行了监管，导致它们被诸如对苯二甲酸二（2-乙基己基）酯（DEHTP）、1,2-环己烷二甲酸二（异壬基）酯（DINCH）和己二酸二（2-乙基己基）酯（DEHA）等替代品所取代。然而，关于人类接触这些替代品的信息，尤其是在儿童等易感亚人群中的信息有限。因此，我们检测了7岁日本学龄儿童体内DEHTP、DINCH和DEHA代谢物的水平及暴露趋势。总共，收集了2012年至2017年期间的180份尿液样本，通过同位素稀释液相色谱-串联质谱法对10种DEHTP、DINCH和DEHA代谢物进行定量分析。分别在95.6%和92.2%的儿童中检测到了DEHTP和DINCH代谢物，未检测到DEHA。这项在2012年至2017年期间每年进行的研究显示，DEHTP代谢物显著增加（<0.05）了5倍，DINCH代谢物增加了2倍。然而，估计的最大内部暴露量仍低于基于健康的指导值和毒理学参考值。日本学龄儿童对DEHTP和DINCH的暴露水平大幅增加。DEHA的相关性较小。有必要开展进一步研究，密切监测不同年龄和更大规模人群中的增长趋势，确定潜在的健康影响以及导致暴露增加的来源，并在必要时进行干预。
