Koch H M, Preuss R, Angerer J
Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, University of Erlangen-Nuremberg, Erlangen, Germany.
Int J Androl. 2006 Feb;29(1):155-65; discussion 181-5. doi: 10.1111/j.1365-2605.2005.00607.x.
Di(2-ethylhexyl)phthalate (DEHP) is a reproductive and developmental toxicant in animals and a suspected endocrine modulator in humans. There is widespread exposure to DEHP in the general population. Patients can be additionally exposed through DEHP-containing medical devices. Toxicokinetic and metabolic knowledge on DEHP in humans is vital not only for the toxicological evaluation of DEHP but also for exposure assessments based on human biomonitoring data. Secondary oxidized DEHP metabolites like mono-(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP), mono-(2-ethyl-5-oxohexyl)phthalate (5oxo-MEHP), mono-(2-ethyl-5-carboxypentyl)phthalate (5cx-MEPP) and mono-[2-(carboxymethyl)hexyl]phthalate (2cx-MMHP) are most valuable biomarkers of DEHP exposure. They represent the major share of DEHP metabolites excreted in urine (about 70% for these four oxidized metabolites vs. about 6% for MEHP); they are immune to external contamination and possibly the ultimate developmental toxicants. Long half-times of elimination make 5cx-MEPP and 2cx-MMHP excellent parameters to measure the time-weighted body burden to DEHP. 5OH-MEHP and 5oxo-MEHP more reflect the short-term exposure. We calculated the daily DEHP intake for the general population (n = 85) and for children (n = 254). Children were significantly higher exposed to DEHP than adults. Exposures at the 95th percentile (21 and 25 microg/kg/day, respectively) scooped out limit values like the Reference Dose (RfD, 20 microg/kg/day) and the Tolerable Daily Intake (TDI, 20-48 microg/kg/day) to a considerable degree. Up to 20-fold oversteppings for some children give cause for concern. We also detected significant DEHP exposures for voluntary platelet donors (n = 12, 38 microg/kg/apheresis, dual-needle technique). Premature neonates (n = 45) were exposed to DEHP up to 100 times above the limit values depending on the intensity of medical care (median: 42 microg/kg/day; 95th percentile: 1,780 microg/kg/day).
邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种动物生殖和发育毒性物质，在人类中被怀疑是一种内分泌调节剂。普通人群中普遍存在DEHP暴露情况。患者还可能通过含DEHP的医疗器械受到额外暴露。了解人类体内DEHP的毒代动力学和代谢知识不仅对DEHP的毒理学评估至关重要，而且对基于人体生物监测数据的暴露评估也至关重要。二级氧化的DEHP代谢产物，如单-（2-乙基-5-羟基己基）邻苯二甲酸酯（5OH-MEHP）、单-（2-乙基-5-氧代己基）邻苯二甲酸酯（5oxo-MEHP）、单-（2-乙基-5-羧基戊基）邻苯二甲酸酯（5cx-MEPP）和单-[2-（羧甲基）己基]邻苯二甲酸酯（2cx-MMHP）是DEHP暴露最有价值的生物标志物。它们占尿液中排出的DEHP代谢产物的主要部分（这四种氧化代谢产物约占70%，而MEHP约占6%）；它们不受外部污染影响，可能是最终的发育毒性物质。5cx-MEPP和2cx-MMHP的消除半衰期长，是衡量DEHP时间加权体内负荷的极佳参数。5OH-MEHP和5oxo-MEHP更能反映短期暴露情况。我们计算了普通人群（n = 85）和儿童（n = 254）的每日DEHP摄入量。儿童接触DEHP的程度明显高于成年人。第95百分位数的暴露量（分别为21和25微克/千克/天）在相当程度上超出了参考剂量（RfD，20微克/千克/天）和可耐受每日摄入量（TDI，20 - 48微克/千克/天）等限值。一些儿童的暴露量高达限值的20倍，令人担忧。我们还检测到自愿血小板捐献者（n = 12，38微克/千克/单采，双针技术）有显著的DEHP暴露。早产儿（n = 45）根据医疗护理强度，接触DEHP的量比限值高出100倍（中位数：42微克/千克/天；第95百分位数：1780微克/千克/天）。
