Background

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.

Methods

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.

Results

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.

Conclusions

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.

中文翻译：

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有机磷酸酯阻燃剂和增塑剂的尿液生物标志物的短期时间变化

背景

通常通过测量尿样中生物标志物的浓度来估算有机磷酸盐阻燃剂和增塑剂（PFR）的暴露量。然而，由于短的生物学半衰期和可变的暴露时间，它们在尿液中的浓度会随着时间变化很大，可能导致暴露错误分类。在这项研究中，我们检查了连续五天的现货尿液样本和24小时合并尿液样本中PFR代谢物的个体内和个体间以及日间和日间变异性。

方法

我们收集了10天健康成年人5天的所有尿样。再过一天，我们收集了24小时收集的尿液样本。通过固相萃取结合高效液相色谱串联质谱分析样品。我们计算了类内相关系数（ICC），以评估早晨空腹和斑点样品中代谢物浓度的重现性。

结果

进行双（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）的系列测量时，观察到良好的重复性。 ，2-羟乙基双（2-丁氧基乙基）磷酸酯（BBOEHEP）和2-乙基-5-羟己基磷酸二苯酯（5-HO-EHDPHP）（ICC：0.396 – 0.599），而磷酸二苯酯（DPHP）和2-乙基己基苯基磷酸酯（EHPHP）的时间变化更大（ICC：0.303和0.234）。仅考虑晨空样本和调整尿液稀释浓度时，重现性显着提高。对于短期时间变异性较差的PFR生物标志物，收集24小时合并尿液可能是一种可靠的选择。

结论

与同一天观察到的变化相比，日间变化较小，这表明收集多个样本可以减少暴露错误分类。观察到的个体之间和个体内部差异的差异是化合物特异性的，并且与暴露的性质（例如饮食与其他暴露途径，多种来源）以及所研究的PFR的个体毒代动力学性质有关。