Prenatal Exposure Level Of Perfluorinated Organic Compounds And Their Precursors And Their Relationship With Fetal Growth And Development

A sensitive and robust method for quantitative analysis of trace levels of precursors of PFCAs and PFSAs in human serum was developed using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) with stable isotope dilution technique. The method was used for determinations of precursors in170cord serum samples from Beijing. The data provided the information on the exposure levels and the composition profiles of precusors in utero. Moreover, we measured the concentrations of PFCs in these cord serum samples with the established technique of analysis.We analysised the relations between PFCs in cord serum and birth outcomes to determine whether PFCs pose an influence on the development of fetus. Finally, we measured thyroxine in147cord blood samples.Then the study was to estimate whether PFCs have an association with the levels of thyroxine in fetus.1. The physical and chemical properties, production, utilization, toxicity, pollution in environment, animals and human were summarized.2. We established a method of UPLC-MS/MS that was to detect fifteen precursors of perfluoroalkyl sulfonates (PFSAs) and perfluoroalkyl carboxylates (PFCAs) in serum. Briefly, TBAS solution was added to sera, then the mixed solution was extracted with aliquots of MTBE. The MTBE aliquots were combined, evaporated to dryness under nitrogen, and reconsituted in0.25mL of methanol and water (1:1). Then the reconstituted solution through0.2μm nylon syringe filter was collected. Chromatographic separation was performed using a Waters ACQUITYTM BEH C18column (50mm×2.1mm×1.7mm). Analyte quantitation was performed in the negative electrospray ionization mode and multiple reaction monitoring (MRM). Three target substances,6:6PFPi,6:8PFPi,8:8PFPi, were externally confirmed by standard addition. Rate of recovery for these three chemicals was from42.01%to112.13%in two standard levels. And the relative standard deviations (RSDs) were lower than10.14%and higher than1.80%. The other twelve substances were quantified with internal standard. Moreover in two standard levels, rate of recovery for these chemicals ranged from70.25%to127.51%. And RSDs were more than1.23%and less than15.45%. And the corresponding LODs and LOQs for all target substances were0.1pg/mL～5pg/mL and0.2pg/mL～10pg/mL. Then we detected these target substances in ten different human serum samples. The levels of few substances were higher than LODs. And the ranges of FOSA-M、N-EtFOSA-M、N-MeFOSAA、 N-EtFOSAA are respectively<LOD～0.94pg/ml、<LOD～10.08pg/ml、<LOD～6.74pg/ml、<LOD～1.04pg/ml. This method, with high sensitivity and accuracy, could meet the actual testing requirements.3. We measured PFHxS, PFOS, PFOA, PFNA, PFDA, PFUdA and15precurors of PFCAs and PFSAs from cord sreum samples (n=170). Six PFCS were individually observed in99.41%,100%,100%,100%,98.25%and91.81%of these samples. And the means was respectively0.238ng/mL,1.242ng/mL,1.300ng/mL,0.229ng/mL,0.118ng/mL and0.121ng/mL. We found there were associations between PFOS and PFHxS, and PFOA in cord serum. We also detected statistically significant associations for PFOA and PFNA, PFDA and PFUdA. These concentrations were lower than a majority of those reported in human sera samples. For these precusors of PFCAs and PFSAs,4:2FTS, FHUEA, FDUEA,6:8PFPi,8:8PFPi and8:2diPAP were not detected in these samples.8:2FTS, FOUEA,6:6PFPi were observed in only <10%of our samples. And all concentrations of these3substances were lower than LOQs. We detected FOSA-M in11and18cord serum samples, with a maximum of2.78pg/mL,3.57p pg/mL. The remaining4substances were dominant precursors of PFCAs and PFSAs.6:2FTS, N-MeFOSAA, N-EtFOSAA,6:2diPAP could be observed in>40%of the cord serum samples. The detection rate of N-MeFOSAA was79.41%, which was the highest. But6:2FTS hold the highest mean of concentration, which was24.17pg/mL. The mean of N-EtFOSAA,6:2diPAP were repectively0.58pg/mL and1.95pg/mL. This study first determined the levels of precurors of PFCAs and PFSAs, which would provide basic data for futher monitoring.4. Previous animal studies have shown that perfluorinated compunds (PFCs) have adverse impacts on birth outcomes, but the results have been inconclusive in humans. We investigated associations between prenatal exposure to PFHxS, PFOS, PFOA, PFNA, PFDA, and PFUdA, and birth outcomes. In total,170mother-infant pairs were recruited from Beijing Haidian maternal and child care service centre Demographic data were obtained by interviewing mothers using a structured questionaire and birth outcomes were extracted from medical records. Cord serum was collected for PFHxS, PFOS, PFOA, PFNA, PFDA and PFUdA analysis by ultra-high-performance liquid chromatography/tandem mass spectrometry. We found no association between PFHxS, PFOS, PFOA, PFNA, PFDA, and PFUdA and newborn length and weight. After adjusting relevent factors, there were no changes of these associations. In our study, we don’t think PFCs can pose any influence on infant development.Thyroid hormones play critical roles in human neurodevelopment and adult neurocognitive functions. Persistent organohalogen pollutants, such as perfluorinated compounds (PFCs), may interfere with thyroid homeostasis and thus exposure to these compunds might represent risk factors for neurologic and cognitive abnormalities. In this study, we measured thyroid parameters[free triiodothyronine (FT3), free thyroxine (FT4), triiodothyronine (T3),thyroxine (T4), thyroid-stimulating-hormone (TSH)] and concertrations of6PFCs, including PFHxS, PFOS, PFOA, PFNA, PFDA, PFUdA, detected in cord serum samples from newborns (n=147). The means of FT3, FT4, T3, T4, TSH are indivually2.05pmol/L,16.04pmol/L,0.98nmol/L,131.33nmol/L,11.91uIU/mL。But we found no statistically signficant associations between FT3, FT4, T3, T4and TSH, and PFHxS, PFOS, PFOA, PFNA, PFDA and PFUdA (P>0.05). Given the ubiquity of PFCs in the environment and the importance of thyroid function to neurodevelopment and neurocognitive endpoints, a confirmatory study is warranted.