Silva Manori J, Reidy John A, Preau James L, Needham Larry L, Calafat Antonia M
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia 30341, USA.
Environ Health Perspect. 2006 Aug;114(8):1158-61. doi: 10.1289/ehp.8865.
Diisononyl phthalate (DINP) is a complex mixture of predominantly nine-carbon branched-chain dialkyl phthalate isomers. Similar to di(2-ethylhexyl) phthalate, a widely used phthalate, DINP causes antiandrogenic effects on developing rodent male fetuses. Traditionally, assessment of human exposure to DINP has been done using monoisononyl phthalate (MINP) , the hydrolytic metabolite of DINP, as a biomarker. However, MINP is only a minor urinary metabolite of DINP. Oxidative metabolites, including mono(carboxyisooctyl) phthalate (MCIOP) , mono(oxoisononyl) phthalate (MOINP) , and mono(hydroxyisononyl) phthalate (MHINP) are the major urinary metabolites in DINP-dosed rats. The urinary concentrations of MINP, MCIOP, MOINP, and MHINP were measured in 129 adult anonymous human volunteers with no known exposure to DINP. Although MINP was not present at detectable levels in any of the samples analyzed, MCIOP, MHINP, and MOINP were detected in 97, 100, and 87% of the urine samples at geometric mean levels equal to 8.6, 11.4, and 1.2 ng/mL, respectively. The concentrations of all three oxidative metabolites were highly correlated with each other (p<0.0001), which confirms a common precursor. MCIOP was excreted predominantly as a free species, whereas MOINP was excreted mostly in its glucuronidated form. The percentage of MHINP excreted either glucuronidated or in its free form was similar. The significantly higher frequency of detection and urinary concentrations of oxidative metabolites than of MINP suggest that these oxidative metabolites are better biomarkers of exposure assessment of DINP than is MINP. Therefore, we concluded that the prevalence of human exposure to DINP is underestimated by using MINP as the sole DINP urinary biomarker.
邻苯二甲酸二异壬酯（DINP）是一种主要由九个碳的支链邻苯二甲酸二烷基酯异构体组成的复杂混合物。与广泛使用的邻苯二甲酸二（2-乙基己基）酯类似，DINP对发育中的啮齿动物雄性胎儿具有抗雄激素作用。传统上，评估人类对DINP的暴露情况是使用邻苯二甲酸单异壬酯（MINP），即DINP的水解代谢产物，作为生物标志物。然而，MINP只是DINP在尿液中的一种次要代谢产物。氧化代谢产物，包括邻苯二甲酸单（羧基异辛基）酯（MCIOP）、邻苯二甲酸单（氧代异壬基）酯（MOINP）和邻苯二甲酸单（羟基异壬基）酯（MHINP），是给予DINP的大鼠尿液中的主要代谢产物。在129名无已知DINP暴露史的成年匿名人类志愿者中测量了MINP、MCIOP、MOINP和MHINP的尿液浓度。虽然在分析的任何样本中MINP都未达到可检测水平，但在97%、100%和87%的尿液样本中检测到了MCIOP、MHINP和MOINP，其几何平均水平分别为8.6、11.4和1.2 ng/mL。所有三种氧化代谢产物的浓度彼此高度相关（p<0.0001），这证实了它们有共同的前体。MCIOP主要以游离形式排泄，而MOINP大多以其葡萄糖醛酸苷化形式排泄。MHINP以葡萄糖醛酸苷化形式或游离形式排泄的百分比相似。氧化代谢产物的检测频率和尿液浓度显著高于MINP，这表明这些氧化代谢产物比MINP更适合作为DINP暴露评估的生物标志物。因此，我们得出结论，仅使用MINP作为DINP尿液生物标志物会低估人类对DINP的暴露普遍性。
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