| Part one:Simultaneous determination of twelve metals in urine samples of electroplating worker by ICP-MSObjective:To establish and validate a simple,accurate and efficient method for the simultaneous determination of 12 metal elements in urine samples,and to assess the exposure levels of heavy metals in the occupational electroplating population.Methods:Based on the inductively coupled plasma mass spectrometry(ICP-MS)high-throughput detection analysis instrument,we detect the content of urinary metals by directly dilution.The urine samples were thaw at room temperature and then were vortexed well.Samples were diluted with 2%dilute acid solution 20 times and the dwell time was set to 0.03s to then be analyzed.Results:The linearity were good with the correlation coefficients were greater than 0.999.The detection limits are in range of 0.001 to 0.180 g/mL and the intra-day precision is less than 10.3%.The inter-day precision is less than 12%and the recovery rates are ranged from 81.3 to 118.2%.The detection of certified reference materials are in the target value within the specified range.Compared with the control group,the contents of nickel,vanadium,cobalt,copper,zinc,arsenic and cadmium levels are higher in occupational group(P<0.05).Conclusion:The method based on ICP-MS for the determination of twelve metal elements is reliable and simple.It can be used especially in the analysis of multiple metals in large population study.Part two:Determination of twelve monoamine neurotransmitters in urine samples of occupational heavy metal exposed populationObjective:To analyze the levels of monoamine neurotransmitter metabolic pathways in urine samples of occupational electroplating worker and control subjects and to analyze the differences.Methods:Based on the targeted metabolomics analysis method,which was developed by ultra-high performance liquid chromatography tandem mass spectrometry in our laboratory previously,we analyzed the levels of 12 monoamine neurotransmitters(dopamine,serotonin,kynurenine)and their metabolites in the urine of the electroplating front-line workers and non-electroplating office workers.Results:After 437 workers were included in the study,they were divided into control group and exposed group.There was no significant difference in age,body mass index and gender index between the two groups(P>0.05),while there are significant differences in smoking,drinking and culture indexes(P<0.05).After the correction with creatinine,tryptophan,5-hydroxyindoleacetic acid,kynurenine,3-methoxy tyramine,and vanillic acid,norepinephrine and adrenaline in the exposed group were higher than those in the exposed group(P<0.05).However,the concentration of 3,4-dihydroxyphenylacetic acid was lower in the exposed group than in the control group(P<0.05).Conclusion:The disorder of monoamine neurotransmitter pathway in urine sample of occupational exposure population was observed.The content of tryptophan,5-hydroxyindoleaceticacid,kynurenine,3-methoxytyramine,norepinephrine and epinephrine were higher than those in the control group.Part three:Analysis of the relationships between the level of metals and monoamine neurotransmitter metabolism in occupationally exposed populationObjectives:To analyze the association between multiple metal exposure levels and monoamine neurotransmitter metabolic pathway and to improve basic support for early warning mechanism in public health and environment.Methods:Based on the method we established previously,we evaluated the content of urinary multiple metals and monoamine neurotransmitters in electroplating and the control population.Multivariate linear regression model was used to analyze the potential association between the exposure of metal elements and the level of metabolic pathway of monoamine neurotransmitters.Restrictive cubic spline function was used to analysis the nonlinear dose-effect relationship.Results:The contents of each metal were divided into four parts,adjusted for the group,age,sex,smoking,drinking,urinary creatinine and BMI,after logarithmic transformation and FDR multiple correction,the levels of vanadium showed a dose-dependent trend with all metabolites(all P<0.05).The level of chromium in the urine was negatively correlated with metabolic pathways(all P<0.05).(? =-0.132,95%CI:-0.238-0.026)and cadmium was positively correlated with 3-HK and 3-HAA levels(?= 0.149).The level of chromium was significantly correlated with the decrease of serotonin(95%CI:-0.004 to-0.302;? = 0.145,95%CI:0.018 to 0.258;?=0.177,95%CI:0.043 to-0.310).There was no significant correlation between the level of copper and the metabolites of the neurotransmitter metabolic pathway(P>0.05).Based on the RSC restricted cubic spline analysis,the assumption of the linear relationship between the manganese and epinephrine was not established(P for overall association = 0.006;P for non-linear association = 0.013),which suggested a nonlinear dose response correlation between manganese and norepinephrine,iron and epinephrine was established(P for overall association = 0.037;P for non-linear association = 0.070,P for overall association<0.001;P for non-linear association =0.070,P for shared association linear association = 0.216).BMI was positively correlated with kynurenine metabolic pathway;but there was no statistically significant correlation with metals(P>0.05).Synergies effects were observed in smoking and vanadium,copper,zinc,arsenic and cadmium on tryptophan,kynurenine,epinephrine,and vanillic acid.Conclusion:Occupational heavy metal exposure is associated with the changes in metabolic pathway of monoamine neurotransmitters.Manganese showed a nonlinear dose-effect relationship with epinephrine and body mass index was closely related with kynurenine metabolic pathway.Synergies effects were observed in smoking and vanadium,copper,zinc,arsenic and cadmium on tryptophan,kynurenine,epinephrine,and vanillic acid.However,the results need to be validated in animals and cell experiments in the further studies.We aimed to analyze the key enzymes and protein related in metabolic pathway in the next step. |
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