【作者】 张静；

【导师】 张立实； 陈锦瑶； 雍莉； 宋阳；

【作者基本信息】 四川大学 ， 公共卫生， 2023， 硕士

【摘要】 第一部分四川省猪肉和鱼肉全氟化合物污染水平和膳食暴露评估目的:调查四川地区猪肉和鱼肉中全氟化合物的污染水平,评估居民经猪肉和鱼肉暴露于全氟化合物的状况。方法:采用2022年国家食品污染物和有害因素风险监测中四川省疾病预防控制中心对四川省内猪肉和鱼肉开展的17种全氟化合物的监测数据,结合2010～2012年中国居民营养与健康状况监测中四川省的膳食调查数据,估算四川居民全氟化合物的估计每日摄入量。结果:2022年共检测了72份猪肉和72份鱼肉（18份带鱼、18份鲢鱼、18份鲫鱼和18份鲤鱼）中的17种全氟化合物水平。猪肉中仅检出了PFOA（检出率2.78%,平均值0.159μg/kg）和PFBA（检出率1.39%,平均值0.312μg/kg）,全氟化合物检出率为4.17%;鱼肉中检出了PFUd A（检出率13.89%,平均值0.209μg/kg）、PFOS（检出率13.89%,平均值0.282μg/kg）、PFTr DA（检出率8.33%,平均值0.190μg/kg）、PFDA（检出率4.17%,平均值0.178μg/kg）、PFDo A（检出率1.39%,平均值0.157μg/kg）五种全氟物质,全氟化合物检出率为20.83%。各类别鱼肉样品全氟化合物检出率由高到低依次为带鱼（38.89%）、鲢鱼（22.22%）和鲫鱼/鲤鱼（11.11%）。2010～2012年四川省居民平均每标准人日摄入猪肉88.37 g,鱼肉6.40 g。通过食用猪肉和鱼肉,以污染平均值和最大值分别计算,总全氟化合物的估计每日摄入量（EDI）分别为0.802 ng/kg/d和3.105 ng/kg/d,其中全氟典型物质PFOA的EDI平均值/最大值为0.234 ng/kg/d/0.751 ng/kg/d,估计每周摄入量（EWI）平均值/最大值为1.638ng/kg/week/5.257 ng/kg/week;PFOS的EDI平均值/最大值为0.030 ng/kg/d/0.254 ng/kg/d,EWI平均值/最大值为0.210 ng/kg/week/1.778 ng/kg/week。结论:四川省猪肉和鱼肉均有被全氟化合物污染的情况,鱼肉较猪肉检出率更高,但污染水平均不高;四川地区居民存在猪肉摄入较多,鱼肉摄入不足的情况,但经猪肉和鱼肉摄入的PFOS、PFOA总量均在安全限值范围内,而经膳食摄入17种全氟化合物总量的安全性还有待进一步研究。第二部分成都市母婴对的全氟化合物暴露和转移探究目的:通过母婴配对样本抽样调查成都市孕妇及其子代的全氟化合物暴露水平及构成谱,阐明全氟化合物的母婴转移模式,并探究全氟化合物对甲状腺功能的影响。方法:在成都市某妇幼保健院招募符合条件的孕妇纳入本研究,通过查询产科病历系统及询问孕妇/家属获得孕妇及新生儿的人口学信息。在分娩前采集静脉血,分娩时采集脐带血、羊水、母尿,婴儿尿在喂奶后2～3小时收集。采用高效液相色谱串联质谱法测定母血清、脐血清、羊水、母尿、婴儿尿中的24种全氟化合物。测定孕妇血清甲状腺功能。采用Friedman检验比较全氟化合物在母血、脐血、羊水中的分布差异;Spearman相关分析探究母血、脐血、羊水两两之间全氟化合物含量的相关性;计算脐血转移效率R_CM、羊水转移效率R_AM探究全氟化合物的母婴转移。回归分析统计孕妇人口学特征、甲状腺功能以及新生儿出生结局与全氟化合物含量的关联。结果:共纳入48对母婴,在母血清中,PFOA、PFOS、PFNA、PFUd A、PFDA、F-53B、6:2 FTSA、OBS、PFHx S检出率均>50%,PFUd A的平均含量最高,为5.427 ng/m L,且为母血清中的主要全氟化合物（占比35.01%）;在脐血清中,PFOA、OBS、PFHp S、PFUd A、F-53B、6:2 FTSA检出率均>50%,6:2 FTSA的平均含量最高,为3.172 ng/m L,且为脐血清中的主要全氟化合物（占比49.98%）。羊水中,PFOA（68.9%）、OBS（68.9%）、PFOS（48.9%）的检出率较高,OBS平均含量最大,为0.406 ng/m L,且为羊水中的主要全氟化合物（占比50.29%）。Spearman相关分析结果显示,脐血清中的PFOA、PFUd A和F-53B与母血清中的含量呈显著正相关（P<0.01）;羊水中PFOA、PFOS与母血清中的含量呈显著正相关（P<0.001）,OBS与母血清中的含量呈显著负相关（P<0.01）。PFOA和OBS在母血清、脐血清和羊水中的总体分布不同（P<0.05）。OBS的脐血转移效率R_CM最高,为2.26,其次是6:2 FTSA,为1.24;OBS的羊水转移效率R_AM也最高,为3.73,大于PFOA（0.08）、PFOS（0.07）。在母尿和婴儿尿中全氟化合物含量均低于检出限。回归分析结果显示,PFOS、PFHx S与孕妇年龄呈显著正相关（P<0.05）,6:2 FTSA与产前BMI呈显著正相关（P<0.05）;新生儿胎龄与F-53B呈显著负相关（P<0.05）。母血清中PFDA水平与甲状腺激素T4水平呈显著正相关（β=19.389,P<0.05）,6:2FTSA与FT4呈显著负相关（β=-0.142,P<0.05）。结论:成都地区的孕妇及其子代均不同程度暴露于全氟化合物,新型全氟（如OBS、F53-B）在母血清、脐血清、羊水中普遍检出;全氟化合物存在母婴转移现象,且新型全氟替代品可能比传统的全氟化合物更易从母亲转移到婴儿;研究结果还表明全氟化合物水平与孕妇年龄、产前BMI、甲状腺激素水平以及新生儿胎龄存在一定相关性。更多还原

【Abstract】 Part 1 Perfluorinated compounds pollution levels and dietary exposure assessment of pork and fish in Sichuan ProvinceObjective:To investigate the pollution level of perfluorinated compounds（PFCs）in pork and fish,and to evaluate the exposure of residents to PFCs through pork and fish in Sichuan.Methods:Based on the monitoring data of 17 PFCs in pork and fish carried out by the Sichuan Provincial Center for Disease Control and Prevention in the 2022National Food Contaminants and Harmful Factors Risk Monitoring,combined with the dietary survey data of Sichuan Province in the 2010-2012 Chinese Residents Nutrition and Health Monitoring,the estimated daily intake（EDI）of PFCs in Sichuan residents was evaluated.Results:A total of 17 PFCs were detected in 72 pork and 72 fish samples（18hairtail,18 silver carp,18 crucian carp and 18 carp）in 2022.Only PFOA（detection rate 2.78%,mean 0.159μg/kg）and PFBA（detection rate 1.39%,mean 0.312μg/kg）were detected in pork,and the detection rate of PFCs was 4.17%.PFUd A（detection rate 13.89%,mean 0.209μg/kg）,PFOS（detection rate 13.89%,mean 0.282μg/kg）,PFTr DA（detection rate 8.33%,mean 0.190μg/kg）,PFDA（detection rate 4.17%,mean 0.178μg/kg）,and PFDo A（detection rate 1.39%,mean 0.157μg/kg）were detected in fish,and the detection rate of PFCs was 20.83%.The detection rates of PFCs in fish samples were in the order of hairtail（38.89%）,silver carp（22.22%）and crucian carp/carp（11.11%）.The average daily intake of pork and fish was 88.37 g and 6.40 g per standard person,respectively.For pork and fish consumption,based on the mean and maximum contamination values,the EDI of PFCs was 0.802 ng/kg/d and 3.105 ng/kg/d,respectively.The EDI mean/maximum value of PFOA was 0.234ng/kg/d/0.751 ng/kg/d,and the estimated weekly intake（EWI）mean/maximum value was 1.638 ng/kg/week/5.257 ng/kg/week.The EDI mean/maximum value of PFOS was 0.030 ng/kg/d/0.254 ng/kg/d,and the EWI mean/maximum value was 0.210ng/kg/week/1.778 ng/kg/week.Conclusion:Both pork and fish were contaminated by PFCs.The detection rate of fish was higher than that of pork,but the pollution level was not high.Most of the residents in Sichuan had high intake of pork and insufficient intake of fish,but the total amount of PFOS,PFOA intaked from pork and fish was within the safety limits,and the safety of the total amount of 17 PFCs through dietary still needs to be further studied.Part 2 Study on the exposure and transfer of perfluorinated compounds in maternal and infant pairs in ChengduObjective:To investigate the exposure level and composition of PFCs in pregnant women and their offspring in Chengdu,clarify the maternal-infant transfer mode of PFCs,and explore the effect of PFCs on thyroid function.Methods:Eligible pregnant women were recruited in a maternal and child health care hospital in Chengdu.The demographic information of pregnant women and newborns was obtained by querying the obstetric medical record system and asking pregnant women/family members.Venous blood was collected before delivery,cord blood,amniotic fluid and maternal urine were collected during delivery,and infant urine was collected 2-3 hours after feeding.High performance liquid chromatography-tandem mass spectrometry was used to determine 24 PFCs in maternal serum,cord serum,amniotic fluid,maternal urine and infant urine.Serum thyroid function of pregnant women was measured.Friedman test was used to compare the distribution of PFCs in maternal serum,cord serum,and amniotic fluid.Spearman correlation analysis was used to explore the correlation among the concentration of PFCs in maternal serum,cord serum,and amniotic fluid.Regression analysis was used to analyze the correlation between maternal demographic characteristics,thyroid function,neonatal birth outcomes and PFCs concentration.The cord serum transfer efficiency R_CM and amniotic fluid transfer efficiency R_AM were calculated to explore the maternal and infant transfer of PFCs.Results:A total of 48 pairs of mothers and infants were included.In maternal serum,the detection rates of PFOA,PFOS,PFNA,PFUd A,PFDA,F-53B,6:2 FTSA,OBS and PFHx S were all>50%.The average concentration of PFUd A was the highest（5.427 ng/m L）,and it was the main PFC in maternal serum（accounting for35.01%）.In cord serum,the detection rates of PFOA,OBS,PFHp S,PFUd A,F-53B and 6:2 FTSA were all>50%.The average concentration of 6:2 FTSA was the highest（3.172 ng/m L）,and it was the main PFC in cord serum（49.98%）.In amniotic fluid,the detection rates of PFOA（68.9%）,OBS（68.9%）and PFOS（48.9%）were higher.The average concentration of OBS was the highest（0.406 ng/m L）,and it was the main PFC in amniotic fluid（50.29%）.Spearman correlation analysis showed that the concentrations of PFOA,PFUd A and F-53B in cord serum were positively correlated with those in maternal serum（P<0.01）.The concentrations of PFOA and PFOS in amniotic fluid were significantly positively correlated with those in maternal serum（P<0.001）,while OBS was significantly negatively correlated with those in maternal serum（P<0.01）.The overall distribution of PFOA and OBS in maternal serum,cord serum and amniotic fluid was different（P<0.05）.The concentration ratios between cord serum and maternal serum(R_CM)of OBS was the highest（2.26）,followed by 6:2FTSA（1.24）.The paired amniotic fluid-maternal serum concentration ratio(R_AM)of OBS was also the highest（3.73）,which was greater than PFOA（0.08）and PFOS（0.07）.The concentrations of PFCs in maternal urine and infant urine were lower than the detection limit.Regression analysis showed that PFOS and PFHx S were positively correlated with maternal age（P<0.05）,and 6:2 FTSA was positively correlated with prenatal BMI（P<0.05）.Neonatal gestational age was negatively correlated with F-53B（P<0.05）.The level of PFDA in maternal serum was positively correlated with thyroid hormone T4 level（β=19.389,P<0.05）,and 6:2 FTSA was negatively correlated with FT4（β=-0.142,P<0.05）.Conclusion:Pregnant women and their offspring in Chengdu are at risk of exposure to PFCs,and new PFCs were commonly detected in maternal serum,cord serum and amniotic fluid.PFCs have the phenomenon of mother-to-child transfer,and new perfluorinated alternatives may be easier to transfer from mother to baby than traditional PFCs.The results also showed that the level of PFCs was correlated with maternal age,prenatal BMI,thyroid hormone levels and neonatal gestational age.更多还原