| Vinyl chloride (VCM) is an important industrial compound. China is a large producer and consumer of vinyl chloride. Different performance resin synthesized by vinyl chloride copolymer has a wide application in various industries in our country. Vinyl chloride is toxic to multiple organs and systems such as heart, lungs, brain and blood.Long-term exposure to VCM can cause peripheral osteolysis and damage to the liver and spleen. Vinyl chloride can cause human liver hemangioma and the VCM was classified as Class 1 carcinogens by IARC in 1987. China’s " occupational exposure limits of harmful factors in workplace " prescribes the PC-TWA of vinyl chloride is 10 mg/m3 and the PC-STEL is 20 mg/m3.Neither China or abroad have not yet developed the biological occupational exposure limits of vinyl chloride.This study aims to help developing the biological occupational exposure limits of vinyl chloride.After vinyl chloride into the body, mostly is excreted with breathing through the lungs in prototype form, and the rest mainly is metabolized and transformed by liver alcohol dehydrogenase (ADH2) and liver microsomal cytochrome P450 enzymes (mainly CYP2E1) in the live and which end metabolic products TCA, hydroxyethyl cysteine and thiodiglycolic acid (TDGA) are excreted by urine; The active intermediate of vinyl chloride produced in the metabolic process (mainly CEO and CAA) can be reacted with DNA, etc. macromolecules and produce four kinds of DNA adducts:sdA,7-(2’-oxoethyl) guanine, sdC and N2,3sdG.Studies have shown that there is a strong correlation between the content of TDGA in urine and the concentration of external exposure of vinyl chloride and the TDGA can be used as a biomarker of vinyl chloride.But there is no a detection methods that sample preparation is simple, easy operation and suitable for promotion. Studies suggest that εdA can be used as the biological effective dose marker of vinyl chloride.Whether the εdC can be used as a biomarker is lacking in corresponding data support now. This paper established a method to detect the TDGA,a metabolite of vinyl chloride,with solid phase extraction-ion chromatography(SPE-IC) and explored that if it is feasible to use εdA and εdC as the exposure biomarkers of vinyl chloride.This paper mainly includes the following two parts:1. Established a SPE-IC method to determine the thiodiglycolic acid in the urine. The samples were prepared by the process of being centrifuged and purified by C18 SPE column before separated by AS 19 anion exchange column and detected by conductivity detector.The thiodiglycolic acid were characterized by the retention time and quantified by peak area and external standard method. The range of linearity was 0.05-50 μg/ml,and the correlation coefficient was 0.9999. The method limit of detection was 0.1μg/ml and the method limit of quantitation was 0.3 μg/ml. The within-run precision was 1.3%-5.1% and the between-run precision was 0.5%-8.8%.The spiked recoveries were 80.1%-104.2%. Samples could be stored at-20*C for at least 14 d. The determination of thiodiglycolic acid could not be interfered by chloroacetic acid, dichloroacetic acid,trichloroacetic acid and other endogenous ionic compounds. This study detected the TDGA both in the exposure group and control group to vinyl chloride by this method. Test results showed that TDGA could be detected in the exposure group mostly, while the TDGA content in control group were less than the detection limit.2. Operatives who were exposed to vinyl chloride were selected as exposure group and the similar seniority career executives who were not exposed to vinyl chloride were selected as control group. In this study, the εdA and εdC in blood samples of workers both in the exposure and control groups were determined by UPLC-ESI-MS/MS with isotope internal standard[15N5]-edA and [15N3]-edC. The TDGA in urine was detected by ion chromatography. The statistical analysis results showed that the εdA and εdC levels in the exposure group were higher than the control group and the difference was significant (P<0.05); sdA and sdC levels were correlated significantly;This research had not found that smoking, alcohol consumption and age could increase the εdA and εdC levels significantly;This study verified the applicability of εdA and εdC as the exposure markers of vinyl chloride initially. |
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