Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany.
REQUIMTE/LAQV-GRAQ, Instituto Superior de Engenharia do Porto do Instituto Politécnico do Porto, Rua Dr. António Bernardino de Almeida, 431, 4200-072 Porto, Portugal; Centro de Investigação em Tecnologias e Sistemas de Informação em Saúde (CINTESIS), Centro de Investigação Médica, 2° piso, edif. Nascente, Faculdade de Medicina da Universidade do Porto, Rua Dr Plácido da Costa s/n, 4200-450 Porto, Portugal.
Environ Int. 2017 Jul;104:25-32. doi: 10.1016/j.envint.2017.03.028. Epub 2017 Apr 11.
Classical ortho-phthalate plasticizers are, due to their endocrine disrupting potency and reproductive toxicity, increasingly replaced by alternative plasticizers. Di(2-ethylhexyl) terephthalate (DEHTP) is one of these substitutes. In this study, we investigated DEHTP exposure in 107 Portuguese children (4-17years old) by analyzing specific DEHTP metabolites in their urine using a newly developed LC-MS/MS method. We could detect the major, specific DEHTP metabolite mono(2-ethyl-5-carboxypentyl) terephthalate (5cx-MEPTP) in 100% of the samples with levels above the limit of quantification in 96% of the samples (median concentration 4.19μg/L; 95th percentile 26.4μg/L; maximum 3400μg/L). Other minor DEHTP metabolites (5OH-MEHTP, 5oxo-MEHTP and 2cx-MMHTP) were detected at lower rates and levels. Daily DEHTP intakes calculated from urinary 5cx-MEPTP levels were generally far below the tolerable daily intake (TDI) of 1000μg/kgbw/d (median 0.67μg/kgbw/d; 95th percentile 6.25μg/kgbw/d; maximum 690μg/kgbw/d). However, for one child the biomarker-derived health-based guidance value (HBM-I value) for 5cx-MEPTP of 1800μg/L was exceeded by about a factor of two. Levels of 5cx-MEPTP and calculated daily DEHTP intakes were higher in normal/under-weight children who nourished on their usual diet compared to overweight/obese children who received nutritional guidance with fresh and unprocessed food (p=0.043 and p<0.001 respectively). This indicates to processed and fatty foodstuff as a major source of DEHTP exposure. Additionally, we found children of lower age having higher DEHTP intakes (p=0.045). Again, foodstuff as a major DEHTP source, together with other child specific DEHTP sources such as mouthing of toys or ingestion of dust might be contributing factors. With the present study, we provide a first data set on the omnipresent DEHTP exposure in children. So far, general levels of DEHTP exposure seem no cause for concern. However, due to the increasing use of DEHTP as an ortho-phthalate substitute, possible increasing exposures in the future should be followed closely.
邻苯二甲酸二（2-乙基己基）酯（DEHTP）是这些替代品之一。在这项研究中，我们通过使用新开发的 LC-MS/MS 方法分析了 107 名葡萄牙儿童（4-17 岁）尿液中特定的 DEHTP 代谢物，来研究 DEHTP 的暴露情况。我们可以在 100%的样本中检测到主要的、特定的 DEHTP 代谢物单（2-乙基-5-羧基戊基）对苯二甲酸酯（5cx-MEPTP），其中 96%的样本中超过定量限（中位数浓度为 4.19μg/L；95%分位数为 26.4μg/L；最大值为 3400μg/L）。其他较少的 DEHTP 代谢物（5OH-MEHTP、5oxo-MEHTP 和 2cx-MMHTP）的检出率和水平较低。根据尿液中 5cx-MEPTP 水平计算的每日 DEHTP 摄入量通常远低于 1000μg/kgbw/d 的可耐受日摄入量（TDI）（中位数 0.67μg/kgbw/d；95%分位数 6.25μg/kgbw/d；最大值 690μg/kgbw/d）。然而，对于一个孩子，5cx-MEPTP 的生物标志物衍生的基于健康的指导值（HBM-I 值）为 1800μg/L，约为两倍。在接受新鲜、未加工食物营养指导的超重/肥胖儿童与正常/体重不足儿童相比，5cx-MEPTP 水平和计算的每日 DEHTP 摄入量更高（分别为 p=0.043 和 p<0.001）。这表明加工和高脂肪食物是 DEHTP 暴露的主要来源。此外，我们发现年龄较小的儿童 DEHTP 摄入量较高（p=0.045）。同样，食物是 DEHTP 的主要来源，再加上儿童特有的其他 DEHTP 来源，如玩具咀嚼或灰尘摄入，可能是造成这种情况的因素。本研究提供了儿童普遍存在的 DEHTP 暴露的第一组数据。到目前为止，DEHTP 暴露的一般水平似乎没有引起关注。然而，由于 DEHTP 作为邻苯二甲酸酯替代品的使用越来越多，未来可能会出现越来越多的暴露情况，应密切关注。
