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 Int. 2021 Jan;146:106147. doi: 10.1016/j.envint.2020.106147. Epub 2020 Nov 1.
Exposure to organophosphate flame retardants and plasticizers (PFRs) is commonly estimated by measuring biomarker concentrations in spot urine samples. However, their concentrations in urine can vary greatly over time due to short biological half-lives and variable exposure, potentially leading to exposure misclassification. In this study, we examined the within- and between-individual and within- and between-day variability of PFR metabolites in spot and 24-hour pooled urine samples during five consecutive days.
We collected all spot urine samples from 10 healthy adults for 5 days. On one additional day, we collected 24-hour pooled urine samples. Samples were analyzed by solid-phase extraction coupled to high-performance liquid chromatography tandem mass spectrometry. We calculated intraclass correlation coefficients (ICCs) to assess the reproducibility of metabolite concentrations in morning void and spot samples.
Fair-to-good reproducibility was observed for serial measurements of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP), 2-hydroxyethyl bis(2-butoxyethyl) phosphate (BBOEHEP) and 2-ethyl-5-hydroxyhexyl diphenyl phosphate (5-HO-EHDPHP) (ICC: 0.396 - 0.599), whereas concentrations of diphenyl phosphate (DPHP) and 2-ethylhexyl phenyl phosphate (EHPHP) were more variable in time (ICC: 0.303 and 0.234). Reproducibility improved significantly when only morning void samples were considered and when concentrations were adjusted for urinary dilution. Collecting 24-hour pooled urine could be a reliable alternative for PFR biomarkers with poor short-term temporal variability.
The between-day variability was minor compared to variability observed within the same day, which suggests that collecting multiple samples could reduce exposure missclassification. Differences in the observed between- and within-individual variance were compound specific and related to both the nature of the exposure (e.g., diet vs other exposure routes, multiple sources) and the individual toxicokinetic properties of the investigated PFRs.
通常通过测量尿样中生物标志物的浓度来估算接触有机磷酸酯阻燃剂和增塑剂（PFR）的情况。然而，由于其生物半衰期短且暴露情况多变，尿液中的浓度在一段时间内会有很大的变化，这可能导致暴露情况出现错误分类。在这项研究中，我们在连续 5 天内检查了单次尿样和 24 小时混合尿样中 PFR 代谢物的个体内和个体间、日内和日间变异性。
我们连续 5 天收集了 10 名健康成年人的所有单次尿样。在另外一天，我们收集了 24 小时混合尿样。通过固相萃取结合高效液相色谱串联质谱法对样品进行分析。我们计算了内类相关系数（ICC），以评估晨尿和单次尿样中代谢物浓度的重现性。
在对双（1,3-二氯-2-丙基）磷酸酯（BDCIPP）、1-羟基-2-丙基双（1-氯-2-丙基）磷酸酯（BCIPHIPP）、2-羟乙基双（2-丁氧基乙基）磷酸酯（BBOEHEP）和 2-乙基-5-羟基己基二苯基磷酸酯（5-HO-EHDPHP）进行的连续测量中，观察到了良好到中等的重现性（ICC：0.396-0.599），而二苯基磷酸酯（DPHP）和 2-乙基己基苯基磷酸酯（EHPHP）的浓度在时间上变化较大（ICC：0.303 和 0.234）。仅考虑晨尿样本和调整尿液稀释后，浓度的重现性显著提高。对于短期时间变异性较差的 PFR 生物标志物，收集 24 小时混合尿样可能是一种可靠的替代方法。
与同一天内观察到的变异性相比，日间变异性较小，这表明多次采样可以减少暴露情况的错误分类。观察到的个体内和个体间差异与暴露的性质（例如，饮食与其他暴露途径、多个来源）以及所研究的 PFR 个体的毒代动力学特性有关。
