Silva M J, Reidy J A, Kato K, Preau J L, Needham L L, Calafat A M
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA.
Biomarkers. 2007 Mar-Apr;12(2):133-44. doi: 10.1080/13547500601066915.
Di-isodecyl phthalate (DiDP), primarily used as a plasticiser, is a mixture of isomers with predominantly ten-carbon branched side chains. Assessment of DiDP exposure has not been conducted before because adequate biomarkers were lacking. In 129 adult volunteers with no known exposure to DiDP, the urinary concentrations of three oxidative metabolites of DiDP: monocarboxyisononyl phthalate (MCiNP), monooxoisodecyl phthalate (MOiDP) and monohydroxyisodecyl phthalate (MHiDP), previously identified in DiDP-dosed rats, were estimated by solid-phase extraction coupled to high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) using the respective oxidative metabolites of di(2-ethylhexyl)phthalate since authentic standards of the DiDP oxidative metabolites were unavailable. Interestingly, the hydrolytic monoester of DiDP, monoisodecyl phthalate (MiDP), was not detected in any of the samples, while MCiNP, MHiDP and MOiDP were detected in 98%, 96% and 85%, respectively, of the samples tested. MCiNP was excreted predominantly in its free form, whereas MOiDP was excreted as its glucuronide. MCiNP, MHiDP and MOiDP eluted as clusters of multiple peaks from the HPLC column probably due to the presence of numerous structurally similar isomers present in commercial DiDP formulations. The urinary concentrations of these oxidative metabolites correlated significantly (p < 0.0001) with each other, thus confirming a common precursor. The urinary concentrations of these DiDP oxidative metabolites also correlated significantly (p < 0.0001) with oxidative metabolites of di-isononyl phthalate (DiNP) suggesting the potential presence of DiNP isomers in commercial DiDP or simultaneous use of DiDP and DiNP in consumer products. The concentrations presented are semiquantitative estimates and should be interpreted cautiously. Nevertheless, the higher frequency of detection and higher urinary concentrations of MCiNP, MHiDP and MOiDP than of MiDP suggest that these oxidative metabolites are better biomarkers for DiDP exposure assessment than MiDP. These data also suggest that unless oxidative metabolites are measured, the prevalence of exposure to DiDP will probably be underestimated.
邻苯二甲酸二异癸酯（DiDP）主要用作增塑剂，是一种异构体混合物，其支链侧链主要含十个碳原子。此前尚未对DiDP暴露进行评估，因为缺乏合适的生物标志物。在129名无已知DiDP暴露史的成年志愿者中，采用固相萃取结合高效液相色谱 - 串联质谱法（HPLC-MS/MS），利用邻苯二甲酸二（2-乙基己基）酯的相应氧化代谢物，对DiDP的三种氧化代谢物：邻苯二甲酸单羧基异壬酯（MCiNP）、邻苯二甲酸单氧代异癸酯（MOiDP）和邻苯二甲酸单羟基异癸酯（MHiDP）的尿浓度进行了估算，因为DiDP氧化代谢物的真实标准品无法获得，而上述三种氧化代谢物此前已在给予DiDP的大鼠中鉴定出来。有趣的是，在任何样本中均未检测到DiDP的水解单酯邻苯二甲酸单异癸酯（MiDP），而在分别98%、96%和85%的受试样本中检测到了MCiNP、MHiDP和MOiDP。MCiNP主要以游离形式排泄，而MOiDP以其葡糖醛酸苷形式排泄。MCiNP、MHiDP和MOiDP从HPLC柱上洗脱为多个峰的簇状，这可能是由于市售DiDP制剂中存在大量结构相似的异构体。这些氧化代谢物的尿浓度彼此之间显著相关（p < 0.0001），从而证实有共同的前体。这些DiDP氧化代谢物的尿浓度与邻苯二甲酸二异壬酯（DiNP）的氧化代谢物也显著相关（p < 0.0001），这表明市售DiDP中可能存在DiNP异构体，或者消费品中同时使用了DiDP和DiNP。给出的浓度是半定量估计值，应谨慎解释。然而，MCiNP、MHiDP和MOiDP的检测频率较高且尿浓度高于MiDP，这表明这些氧化代谢物比MiDP更适合作为DiDP暴露评估的生物标志物。这些数据还表明，除非测量氧化代谢物，否则DiDP的暴露流行率可能会被低估。
