Toxicological Center, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium.
Hokkaido University Center for Environmental and Health Sciences, Kita 12, Nishi 7, Kita-ku Sapporo, 060-0812, Japan.
Environ Res. 2020 Dec;191:110248. doi: 10.1016/j.envres.2020.110248. Epub 2020 Sep 24.
Due to international regulations, commonly used phthalates such as di(2-ethylhexyl) phthalate (DEHP) are being replaced by other phthalates, such as di-isononyl phthalate (DINP), and di-isodecyl phthalate (DIDP) and by alternative plasticizers (APs) with similar chemical characteristics, like di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), di(2-ethylhexyl) terephthalate (DEHTP), or di-(2-ethylhexyl) adipate (DEHA). Urinary concentrations of metabolites are frequently used in the exposure assessment of non-persistent chemicals and for biomonitoring purposes, the intra- and inter-day variability of the metabolites should be known. However, the short-term variability of AP and several phthalate biomarkers has not been investigated yet. In this study, we collected all spot samples from 10 healthy adults for 5 consecutive days and 24h pooled urine on one additional day to investigate the short-term variability of 22 biomarkers of phthalates and APs. Metabolites of DEP, DEHP, DiBP, DnBP, DBzP, DINP and DIDP were found in high detection frequencies, while metabolites of most APs were found in approximately 50% of the samples. The short-term reproducibility of metabolites with diet as primary source (DEHP, DINP, DIDP) was poor (intraclass correlation coefficient - ICC < 0.4), whereas biomarkers of DEP, DnBP, DiBP and BBzP showed good consistency, most likely due to more continuous sources resulting in less between-day variance. ICC values of AP metabolites were similar to those of DEHP, but more studies are required to confirm these findings. Overall, reproducibility improved considerably when values were corrected for urinary dilution and when only morning voids samples were considered. Levels in morning voids samples were consistent for 5 days and comparable to 24-h pooled urine for all metabolites except for OH-MEHTP, sum DINP and sum DIDP, which supports the use of morning voids in human biomonitoring studies.
由于国际法规的要求，邻苯二甲酸二（2-乙基己基）酯（DEHP）等常用邻苯二甲酸酯正被其他邻苯二甲酸酯替代，例如邻苯二甲酸二异壬酯（DINP）和邻苯二甲酸二异癸酯（DIDP），以及具有相似化学特性的替代增塑剂（APs），如邻苯二甲酸二异壬基环己烷-1,2-二羧酸酯（DINCH）、对苯二甲酸二（2-乙基己基）酯（DEHTP）或己二酸二（2-乙基己基）酯（DEHA）。代谢物的尿浓度常用于非持久性化学物质的暴露评估和生物监测目的，因此应了解代谢物的日内和日间变异性。然而，目前还没有研究过 AP 和几种邻苯二甲酸酯生物标志物的短期变异性。在这项研究中，我们连续 5 天收集了 10 名健康成年人的所有点样，并在第 6 天收集了 24 小时混合尿液，以研究 22 种邻苯二甲酸酯和 AP 生物标志物的短期变异性。DEP、DEHP、DiBP、DnBP、DBzP、DINP 和 DIDP 的代谢物被发现具有高检测频率，而大多数 AP 的代谢物在大约 50%的样本中被发现。作为主要来源的代谢物的短期重现性较差（内类相关系数 - ICC < 0.4），而 DEP、DnBP、DiBP 和 BBzP 的生物标志物一致性较好，这很可能是由于更连续的来源导致日内差异较小。AP 代谢物的 ICC 值与 DEHP 相似，但需要更多的研究来证实这些发现。总体而言，当值校正尿液稀释和仅考虑晨尿样本时，重现性有了显著提高。除了 OH-MEHTP、DINP 总和 DIDP 总和外，5 天的晨尿样本水平一致，与所有代谢物的 24 小时混合尿液相当，这支持在人体生物监测研究中使用晨尿。
