Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, United States.
Chemosphere. 2011 Jan;82(3):431-6. doi: 10.1016/j.chemosphere.2010.09.052. Epub 2010 Oct 15.
Di-n-pentyl phthalate (DPP) is used mainly as a plasticizer in nitrocellulose. At high doses, DPP acts as a potent testicular toxicant in rats. We administered a single oral dose of 500 mg kg(-1)bw of DPP to adult female Sprague-Dawley rats (N=9) and collected 24-h urine samples 1d before and 24- and 48-h after DPP was administered to tentatively identify DPP metabolites that could be used as exposure biomarkers. At necropsy, 48 h after dosing, we also collected serum. The metabolites were extracted from urine or serum, resolved with high performance liquid chromatography, and detected by mass spectrometry. Two DPP metabolites, phthalic acid (PA) and mono(3-carboxypropyl) phthalate (MCPP), were identified by using authentic standards, whereas mono-n-pentyl phthalate (MPP), mono(4-oxopentyl) phthalate (MOPP), mono(4-hydroxypentyl) phthalate (MHPP), mono(4-carboxybutyl) phthalate (MCBP), mono(2-carboxyethyl) phthalate (MCEP), and mono-n-pentenyl phthalate (MPeP) were identified based on their full scan mass spectrometric fragmentation pattern. The ω-1 oxidation product, MHPP, was the predominant urinary metabolite of DPP. The median urinary concentrations (μg mL(-1)) of the metabolites in the first 24h urine collection after DPP administration were 993 (MHPP), 168 (MCBP), 0.2 (MCEP), 222 (MPP), 47 (MOPP), 26 (PA), 16 (MPeP), and 9 (MCPP); the concentrations of metabolites in the second 24 h urine collection after DPP administration were significantly lower than in the first collection. We identified some urinary metabolic products in the serum, but at much lower levels than in urine. Because of the similarities in metabolism of phthalates between rats and humans, based on our results and the fact that MHPP can only be formed from the metabolism of DPP, MHPP would be the most adequate DPP exposure biomarker for human exposure assessment. Nonetheless, based on the urinary levels of MHPP, our preliminary data suggest that human exposure to DPP in the United States is rather limited.
邻苯二甲酸二戊酯（DPP）主要用作硝化纤维素中的增塑剂。在高剂量下，DPP 可在大鼠中充当强效睾丸毒物。我们给成年雌性 Sprague-Dawley 大鼠（N=9）单次口服 500mg/kg bw 的 DPP，并在给药后 1d 以及 24 和 48h 收集 24h 尿液样本，以初步确定可用作暴露生物标志物的 DPP 代谢物。在 48h 处死时，我们还收集了血清。将代谢物从尿液或血清中提取出来，用高效液相色谱法进行分离，并用质谱法进行检测。使用标准品鉴定了两种 DPP 代谢物，邻苯二甲酸（PA）和单（3-羧丙基）邻苯二甲酸酯（MCPP），而单正戊基邻苯二甲酸酯（MPP）、单（4-氧代戊基）邻苯二甲酸酯（MOPP）、单（4-羟基戊基）邻苯二甲酸酯（MHPP）、单（4-羧丁基）邻苯二甲酸酯（MCBP）、单（2-羧乙基）邻苯二甲酸酯（MCEP）和单正戊基邻苯二甲酸酯（MPeP）则根据其全扫描质谱裂解模式进行鉴定。ω-1 氧化产物 MHPP 是 DPP 的主要尿液代谢物。在 DPP 给药后首次 24h 尿液收集期间，代谢物的中位数尿液浓度（μg/mL）分别为 993（MHPP）、168（MCBP）、0.2（MCEP）、222（MPP）、47（MOPP）、26（PA）、16（MPeP）和 9（MCPP）；在 DPP 给药后第二次 24h 尿液收集期间，代谢物浓度明显低于首次收集。我们在血清中鉴定出一些代谢产物，但水平远低于尿液。由于大鼠和人类之间邻苯二甲酸酯的代谢相似，基于我们的结果以及只有通过 DPP 代谢才能形成 MHPP 的事实，MHPP 将是评估人类接触 DPP 的最适当的生物标志物。尽管如此，基于 MHPP 的尿液水平，我们的初步数据表明，美国人类接触 DPP 的情况相当有限。
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