脐带血中邻苯二甲酸酯类代谢产物含量测定及其影响因素分析

发布时间：2018-03-15 08:06

本文选题：邻苯二甲酸酯代谢产物　切入点：脐带血　出处：《天津医科大学》2013年硕士论文　论文类型：学位论文

【摘要】：研究目的邻苯二甲酸酯类化合物主要用作增塑剂,增大产品的可塑性和提高产品的强度,用途广泛且使用量大,是一类已知的环境内分泌干扰物,可以影响人类和动物的正常内分泌活动,从而对生殖发育系统造成潜在不良影响。近年来,随着工业的发展,人类对PAEs的用量不断增加,PAEs通过各种途径不断释放进入环境,已经成为全球范围内最普遍的污染物之一。人体可通过多种途径摄入PAEs,大量流行病学调查显示人类普遍暴露于PAEs。本研究在优化脐带血清中PAEs代谢产物检测方法的基础上,通过测定脐带血清中五种PAEs代谢产物,评价胎儿出生前经母体PAEs的暴露水平。结合问卷调查内容,初步探讨影响胎儿经母体PAEs暴露水平的主要因素,为及时采取措施预防出生前经母体PAEs暴露产生的危害提供科学依据。研究方法该研究选取天津地区96名自愿参加本研究的待产孕妇,排除职业暴露史和疾病史。收集每名孕妇分娩时的脐带血,采用固相萃取高效液相色谱串联质谱法测定脐血清中的五种邻苯二甲酸酯DMP、DEP、DBP、BBP、DEHP各自的代谢产物MMP、MEP、MBP、MBzP、MEHP。所有调查对象均接受流行病学问卷调查,主要调查内容包括：一般人口统计学特征、职业暴露史、社会经济状况等,婚育史及疾病史,个人嗜好(吸烟、饮酒情况)。结合问卷内容及脐带血中PAEs代谢产物的测定结果,采用Logistic回归分析,初步探讨影响胎儿经母体PAEs暴露水平的主要因素。研究结果 (1)本研究优化了同时测定脐带血清中五种PAEs代谢产物的方法,该方法采用p-葡萄糖酸酐酶水解脐带血清中结合型邻苯二甲酸酯代谢物,用磷酸及有机溶剂(乙腈)去除脐带血清中的蛋白质,排除了蛋白质对测定结果的干扰,酶解后的溶液采用固相萃取法富集净化,采用HPLC-MS法对脐带血清中五种邻苯二甲酸酯代谢产物进行测定,该方法回归方程的回归系数均0.99,平均回收率在80.59%～85.75%之间,RSD在3.09%-3.91%之间,检出限为0.109μg/L-0.579μg/L。 (2)本研究96例脐血清样本中MMP、MEP、MBP、MBzP、MEHP的检出率分别为98.96%、94.79%、79.17%、93.75%、98.96%,检出量中位数(P25～P75)分别为26.92μg/L (12.50μg/L～59.13μg/L)29.84μg/L)、16.97μg/L(4.03μg/L～40.43μg/L)、3.23μg/L(0.97μg/L-6.76μg/L)、5.48μg/L(3.52μg/L～8.25μg/L)。 (3)经过单因素、多因素有序Logistic回归分析发现,孕期烫染头发可能为影响DEP、BBP暴露的危险因素,OR值分别为3.28(95%CI:1.55-6.95)和4.79(95%CI：2.23～10.3)。孕期使用塑料杯子可能为影响DEHP暴露的危险因素,OR值为2.66(95%CI.1.21-5.85)。结论本研究建立并优化了同时测定脐带血清中五种PAEs代谢产物的固相萃取高效液相色谱-串联质谱法,该方法回收率较高,重现性较好,适用于脐带血清中五种邻苯二甲酸单酯的同时测定。应用该方法测定96例胎儿脐血清中五种PAEs代谢产物的含量,测定结果表明,胎儿可经母体暴露于多种PAES。分析影响孕期PAEs暴露的因素,发现孕期烫染头发可能为影响DEP、BBP暴露的危险因素,孕期使用塑料杯子可能为影响DEHP暴露的危险因素。
[Abstract]:research objective
Two phthalate acid esters mainly used as plasticizers, plastic products increase and improve product strength, wide purpose and usage, is a kind of environmental endocrine disruptors known, normal endocrine activity can affect human and animal, and the reproductive system caused by potential adverse effects. In recent years, along with the industry the development of human beings, the amount of PAEs increasing, PAEs through a variety of ways to continue to release into the environment, has become one of the most common pollutants in the world. The human body through a variety of ways a large number of epidemiological studies show that the uptake of PAEs in PAEs. based on the research of optimization method for detection of PAEs metabolites in the serum of umbilical cord generally exposed to human, through the determination of five metabolites of PAEs in umbilical cord serum, evaluation of the fetus before birth by exposure to maternal PAEs. Combined with the content of questionnaire, preliminary exploration The main factors that affect the maternal PAEs exposure level provide a scientific basis for timely measures to prevent the risk of maternal PAEs exposure.
research method
This study selected 96 in Tianjin participated in this study of pregnant women, excluding occupation exposure history and history of disease. Collect childbirth every pregnant woman when the umbilical cord blood by solid phase extraction and high performance liquid chromatography tandem mass spectrometry method for the determination of cord blood serum in five adjacent benzene two formic acid ester DMP, DEP, DBP, BBP, DEHP the metabolites of MMP, MEP, MBP, MBzP, MEHP.
All subjects received questionnaire survey, the main research contents include: general demographic characteristics, occupation exposure, social economic status, marital history and disease history, personal habits (smoking, drinking). The determination results of PAEs metabolites questionnaire and umbilical cord blood, using Logistic regression analysis, the main factors preliminary study on the effect of the fetal maternal PAEs exposure level.
Research results
(1) the optimization method for the simultaneous determination of five metabolites of PAEs in umbilical cord serum, the method using p- glucose anhydride hydrolysis cord serum combined phthalate two carbamate metabolites with phosphoric acid and organic solvent (acetonitrile) removal of the umbilical cord serum protein, protein eliminated the interference on the determination results. Solution after enzymatic hydrolysis by solid phase extraction and enrichment purification of umbilical cord serum concentrations of five kinds of phthalate acid esters of two metabolites were measured by HPLC-MS method, the method of regression coefficient of regression equation is 0.99, the average recovery rate was 80.59% ~ 85.75%, RSD between 3.09%-3.91%, the detection limit is 0.109 g/L-0.579 g/L.
(2) in this study, 96 cases of umbilical cord blood serum samples of MMP, MEP, MBP, MBzP, MEHP detection rates were 98.96%, 94.79%, 79.17%, 93.75%, 98.96%, median detectable amount (P25 ~ P75) were 26.92 g/L (12.50 g/L ~ 59.13 g/L) 29.84 g/L), 16.97 g/L (4.03 g/L ~ 40.43 g/L), 3.23 g/L (0.97 g/L-6.76 g/L), 5.48 g/L (3.52 g/L ~ 8.25 g/L).
(3) after single factor, multi factor ordered Logistic regression analysis found that pregnancy hot hair dyes may affect DEP, risk factors of BBP exposure, the OR values were 3.28 (95%CI:1.55-6.95) and 4.79 (95%CI:2.23 ~ 10.3). The use of plastic cups during pregnancy may affect the risk of DEHP exposure factors, the OR value is 2.66 (95%CI.1.21-5.85).
conclusion
In this study, we established and optimized the simultaneous determination of five kinds of umbilical cord serum metabolites of PAEs in solid phase extraction and high performance liquid chromatography tandem mass spectrometry method, the high recovery rate, good repeatability, suitable for determination of five phthalic acid ester two cord serum at the same time. The content was measured in 96 patients with five fetal umbilical blood. Metabolites of PAEs in the application of this method, the results show that the fetus after maternal exposure to a variety of PAES. analysis on the influencing factors of prenatal PAEs exposure during pregnancy, that hot hair dyes may affect DEP, risk factors of BBP exposure during pregnancy, the use of plastic cup may affect the risk of DEHP exposure factors.

【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R114

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