Di(2-ethylhexyl)phthalate (DEHP): human metabolism and internal exposure - an update and latest results
Di(2-ethylhexyl)phthalate (DEHP): human metabolism and internal exposure - an update and latest results
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DOI：
10.1111/j.1365-2605.2005.00607.x
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发表时间：
2006-02-01
影响因子：
--
通讯作者：
Angerer, J
中科院分区：
文献类型：
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作者：
Koch, HM;Preuss, R;Angerer, J
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，对人类可能是一种内分泌调节剂。在普通人群中广泛接触DEHP。患者可以通过含有DEHP的医疗设备额外暴露。DEHP在人体内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是至关重要的。DEHP二次氧化代谢产物如邻苯二甲酸单(2-乙基-5-羟基己基)(5OH-MEHP)、邻苯二甲酸单(2-乙基-5-氧基己基)(5oxo-MEHP)、邻苯二甲酸单(2-乙基-5-羧基戊基)邻苯二甲酸单酯(5cx-MEPP)和邻苯二甲酸单[2-(羧甲基)己基]邻苯二甲酸单(2cx-MMHP)是DEHP暴露最有价值的生物标志。它们代表了尿液中排出的DEHP代谢物的主要份额(这四种氧化代谢物约占70%，而MEHP约占6%)；它们对外部污染和可能最终的发育毒物具有免疫力。较长的消除半衰期使5cx-MEPP和2cx-MMHP成为测量DEHP时间加权体重的最佳参数。5OH-MEHP和5oxo-MEHP更能反映短期暴露。我们计算了普通人群(n=85)和儿童(n=254)的DEHP日摄入量。儿童接触DEHP的比例明显高于成人。第95个百分位数(分别为21和25微克/千克/天)的暴露量在相当程度上超出了参考剂量(RfD，20微克/千克/天)和可耐受日摄入量(TDI，20-48微克/千克/天)等限值。一些儿童的过度放牧高达20倍，令人担忧。我们还在自愿献血者中检测到显著的DEHP暴露(n=12，38mUg/kg/采集法，双针技术)。根据医疗护理强度的不同，早产儿(n=45)暴露于DEHP超过限值100倍(中位数：42微克/公斤/天；第95个百分位数：1780微克/公斤/天)。
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 mu g/kg/day, respectively) scooped out limit values like the Reference Dose (RfD, 20 mu g/kg/day) and the Tolerable Daily Intake (TDI, 20-48 mu g/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 mu g/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 mu g/kg/day; 95th percentile: 1780 mu g/kg/day).