Koch Holger M, Drexler Hans, Angerer Jürgen
Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, University of Erlangen-Nuremberg, Schillerstr. 25/29, D-91054 Erlangen, Germany.
Int J Hyg Environ Health. 2004 Jan;207(1):15-22. doi: 10.1078/1438-4639-00270.
Di(2-ethylhexyl)phthalate (DEHP) is the main plasticizer for polyvinyl chloride (PVC) products. It has become widely spread in our environment and among people. DEHP is suspected to be responsible for endocrine-disruptor-like effects in mankind. Children are probably most susceptible to these endocrine effects. In this study we determined the internal exposure of nursery school children (aged 2-6 years) to DEHP and compared it to their parents' and teachers' exposure. The DEHP-metabolites mono(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP), mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP) and mono(2-ethylhexyl)phthalate (MEHP) were determined in first morning urine. The sum of the three DEHP metabolites in children's and in adults' urine was 90.0 and 59.1 micrograms/l respectively (median values; p = 0.074). Concentrations of the secondary metabolites 5OH-MEHP (median: 49.6 vs. 32.1 micrograms/l; p = 0.038) and 5oxo-MEHP (median: 33.8 vs. 19.6 micrograms/l; p = 0.015) were significantly higher in children than in adults. MEHP concentrations were low both in adults and children (median: 6.6 micrograms/l vs. 9.0 micrograms/l). Creatinine adjusted values should more accurately reflect the dose taken up with respect to body weight when comparing children with adults. Total creatinine adjusted DEHP metabolites in urine were significantly higher in children than in adults (median values: 98.8 vs. 50.9 micrograms/g creatinine; p < 0.0001). This also applied to the concentrations of both secondary metabolites 5OH-MEHP (55.8 vs. 28.1 micrograms/g creatinine; p < 0.0001) and 5oxo-MEHP (38.3 vs. 17.2 micrograms/g creatinine; p < 0.0001). Creatinine corrected concentrations for the monoester MEHP in children and adults were very similar (8.7 vs. 8.6 micrograms/g creatinine; p = 0.908). Based on the sum of the three determined metabolites we estimated the DEHP dose (in microgram/kg body-weight) taken up by children to be about twice as high as the dose taken up by adults. Routes of the ubiquitous exposure to DEHP remain indistinct. In children's urine the mean relative ratios of MEHP to 5OH-MEHP to 5oxo-MEHP were 1 to 7.1 to 4.9, in adults they were 1 to 3.4 to 2.1. This might indicate an enhanced oxidative metabolism in children. To date no information on the biological activity and toxicity of oxidative metabolites of DEHP is available. Since these are the major metabolites of DEHP toxicological data on these metabolites is urgently needed.
邻苯二甲酸二(2-乙基己基)酯(DEHP)是聚氯乙烯(PVC)产品的主要增塑剂。它已在我们的环境中广泛传播,并存在于人群中。DEHP被怀疑会对人类产生类似内分泌干扰物的影响。儿童可能最易受到这些内分泌影响。在本研究中,我们测定了幼儿园儿童(2至6岁)体内DEHP的暴露情况,并将其与他们的父母和教师的暴露情况进行比较。在晨尿中测定了DEHP的代谢产物单(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)和单(2-乙基己基)邻苯二甲酸酯(MEHP)。儿童和成人尿液中三种DEHP代谢产物的总和分别为90.0和59.1微克/升(中位数;p = 0.074)。儿童体内次要代谢产物5OH-MEHP(中位数:49.6对32.1微克/升;p = 0.038)和5oxo-MEHP(中位数:33.8对19.6微克/升;p = 0.015)的浓度显著高于成人。成人和儿童体内MEHP的浓度都很低(中位数:6.6微克/升对9.0微克/升)。在比较儿童和成人时,肌酐校正值应能更准确地反映相对于体重摄入的剂量。儿童尿液中总肌酐校正后的DEHP代谢产物显著高于成人(中位数:98.8对50.9微克/克肌酐;p < 0.0001)。这也适用于两种次要代谢产物5OH-MEHP(55.8对28.1微克/克肌酐;p < 0.0001)和5oxo-MEHP(38.3对17.2微克/克肌酐;p < 0.0001)的浓度。儿童和成人单酯MEHP的肌酐校正浓度非常相似(8.7对8.6微克/克肌酐;p = 0.908)。根据所测定的三种代谢产物的总和,我们估计儿童摄入的DEHP剂量(以微克/千克体重计)约为成人摄入剂量的两倍。普遍存在的DEHP暴露途径仍不明确。儿童尿液中MEHP与5OH-MEHP与5oxo-MEHP的平均相对比例为1比7.1比4.9,成人为1比3.4比2.1。这可能表明儿童体内氧化代谢增强。迄今为止,尚无关于DEHP氧化代谢产物的生物活性和毒性的信息。由于这些是DEHP的主要代谢产物,迫切需要关于这些代谢产物的毒理学数据。