Abstract：
Much evidence on the adverse health effects of endocrine-disrupting chemicals (EDCs) has accumulated during recent decades. EDCs are commonly found in various foods and personal care products (PCP). Data documenting a diurnally varying EDC metabolism in humans is scarce. This study examined (i) the time-of-day effect on the diurnal magnitude and variance of urinary biomarkers of exposure to EDCs, and (ii) the association between EDC exposures and oxidative damage in a Norwegian adult subpopulation. This was a cross-sectional panel study using biobanked samples from the EuroMix project. During a typical weekday, participants were asked to collect all day’s urine voids and record dietary and PCP habitual uses in a diary. Collected time stamps of urine voids were classified into three distinct periods in the day (morning 6 a.m.−12 p.m., mid-day 12 p.m.−6 p.m., evening 6 p.m.−6 a.m.). Questionnaires regarding demographic characteristics, personal care product usage, and dietary habits were completed. Urinary levels of EDCs (phthalates, parabens, and bisphenols) were measured using mass spectrometry and adjusted for urinary volume using specific gravity. Urinary 4-hydroxynonenal (4HNE), a lipid peroxidation marker, was measured using an immunoassay kit. Linear mixed-effect models identified EDCs under the influence of a diurnal variation effect that was adjusted for dietary habits and PCP use and examined associations between EDC and 4HNE. p-values were FDR-adjusted. Most phthalates appeared to be diurnally varying with higher urinary levels towards the evening (q < 0.001) than those measured during mid-day; this strong diurnal variation effect was not present for parabens and bisphenols. Significant (q < 0.001) positive associations were observed between all phthalates, parabens, and bisphenols (except bisphenol S) and 4HNE. This study’s findings highlighted the diurnal variation of excretion for certain EDC, but not for others, in real-life conditions. The degree of EDC chronotoxicity in distinct diurnal windows of the day warrants further investigation with longitudinal human studies.
摘要：
近几十年来，已经积累了许多关于内分泌干扰化学物质（EDC）对健康的不利影响的证据。EDC通常存在于各种食品和个人护理产品(PCP)中。记录人类昼夜变化的EDC代谢的数据很少。这项研究检查了（i）一天中的时间对暴露于EDC的尿液生物标志物的昼夜大小和方差的影响，和（ii）挪威成人亚群中EDC暴露与氧化损伤之间的关联。这是一项横断面小组研究，使用EuroMix项目的生物样本。在一个典型的工作日，参与者被要求收集全天尿样,并在日记中记录饮食和PCP习惯性使用.收集的尿液空隙时间戳分为一天中的三个不同时期（上午6点至下午12点，中午12:00-下午6:00，晚上6点-上午6点)。关于人口统计特征的问卷调查，个人护理产品的使用，和饮食习惯完成。尿液中EDC的水平（邻苯二甲酸盐，对羟基苯甲酸酯,和双酚）使用质谱法测量，并使用比重调整尿量。尿4-羟基壬烯醛（4HNE），脂质过氧化标记，使用免疫测定试剂盒测量。线性混合效应模型确定了受昼夜变化效应影响的EDC，该效应根据饮食习惯和PCP的使用进行了调整，并检查了EDC和4HNE之间的关联。p值是FDR调整的。大多数邻苯二甲酸酯似乎是昼夜变化的，其尿液水平比中午时高（q<0.001）；对羟基苯甲酸酯和双酚不存在这种强烈的昼夜变化效应。在所有邻苯二甲酸酯之间观察到显着（q<0.001）正相关，对羟基苯甲酸酯,和双酚（双酚S除外）和4HNE。这项研究的发现强调了某些EDC排泄的日变化，但不是为了其他人，在现实生活中。在当天不同的昼夜窗口中，EDC的时间毒性程度值得通过纵向人体研究进行进一步研究。
