Within-person variability in urinary phthalate metabolite concentrations: measurements from specimens after long-term frozen storage.
Within-person variability in urinary phthalate metabolite concentrations: measurements from specimens after long-term frozen storage.
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DOI：
10.1038/jes.2009.17
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发表时间：
2010-03
影响因子：
4.5
通讯作者：
Wilcox AJ
中科院分区：
文献类型：
--
作者：
Baird DD;Saldana TM;Nepomnaschy PA;Hoppin JA;Longnecker MP;Weinberg CR;Wilcox AJ
实验室研究表明，在发育过程中暴露于邻苯二甲酸盐会造成不良影响，特别是对男性。通过采集妊娠期间的尿液、长期储存和在评估后代健康时测量邻苯二甲酸酯代谢物，将有助于人类研究。我们的目的是测量长期冷冻储存后的尿邻苯二甲酸酯代谢物，使用这些测量值来评估两周和四周间隔内的女性内变异性，并确定月经周期的阶段是否影响代谢物水平。从1983-1985年收集的60名妇女每日第一次晨尿标本中选择样本，并冷冻储存。每名妇女以大约两周的间隔选择三个样本，包括卵泡期和黄体期样本。通过质谱法测量了五种邻苯二甲酸酯的七种代谢物。采用相关性、混合模型回归和Wilcoxon符号秩检验进行统计分析。在长期储存后的样本中测量的肌酐校正的尿邻苯二甲酸酯代谢物浓度倾向于具有类似的右偏分布，尽管浓度略高于最近收集的美国样本报告的浓度。同一样本中邻苯二甲酸二（2-乙基己基）酯的三种代谢物浓度高度相关（Pearson r = 0.85 - 0.97）。邻苯二甲酸二乙酯和邻苯二甲酸苄丁酯代谢物在4周间隔内的重现性为中等（组内相关系数，ICC分别为0.48和0.53），而其他5种代谢物的ICC较低（0.21 - 0.37）。月经期与代谢物浓度无关。尽管在长期储存前后均未测量相同的样品，但结果表明，长期样品储存后邻苯二甲酸酯代谢物的测量结果与最近收集的标本报告的分布和时间可靠性大致相似。这些发现支持使用在人类妊娠相关阶段收集的储存尿液样本来研究邻苯二甲酸酯暴露对后期结局的影响。
Laboratory studies show that exposure to phthalates during development can cause adverse effects, especially for males. Studies in humans would be facilitated by collection of urine during pregnancy, long-term storage, and measurement of phthalate metabolites at the time that offspring health is assessed. Our aims were to measure urinary phthalate metabolites after long-term freezer storage, to use those measurements to evaluate within-woman variability over two and four-week intervals, and to determine if the phases of the menstrual cycle affect metabolite levels. Samples were selected from daily first-morning urine specimens collected by 60 women and stored frozen since 1983-1985. Three specimens per woman were selected at approximately two-week intervals to include both follicular and luteal phase samples. Seven metabolites of five phthalates were measured by mass spectrometry. Statistical analyses were conducted with correlation, mixed model regression, and the Wilcoxon signed rank test. Creatinine-corrected urinary phthalate metabolite concentrations measured in samples after long-term storage tended to have a similar right-skewed distribution, though with somewhat higher concentrations than those reported for recently-collected U.S. samples. The concentrations of three metabolites of di(2-ethylhexyl)phthalate in the same specimen were very highly correlated (Pearson r = 0.85 – 0.97). Reproducibility over a 4-week interval was moderate for the metabolites of diethyl phthalate and benzylbutyl phthalate (intraclass correlation coefficients, ICCs, = 0.48 and 0.53, respectively), while five other metabolites had lower ICCs (0.21 – 0.37). Menstrual phase was not related to metabolite concentrations. Though the same samples have not been measured both before and after long-term storage, results suggest that measurement of phthalate metabolites after long-term sample storage yield generally similar distributions and temporal reliability as those reported for recently-collected specimens. These findings support the use of stored urine specimens collected during the relevant stage of human pregnancy to investigate the influence of phthalate exposures on later outcomes.