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- Abrahamsson, Dimitri, et al.
(författare)
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In Silico Structure Predictions for Non-targeted Analysis : From Physicochemical Properties to Molecular Structures
- 2022
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Ingår i: Journal of the American Society for Mass Spectrometry. - : American Chemical Society (ACS). - 1044-0305 .- 1879-1123. ; 33:7, s. 1134-1147
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Tidskriftsartikel (refereegranskat)abstract
- While important advances have been made in high-resolution mass spectrometry (HRMS) and its applications in non-targeted analysis (NTA), the number of identified compounds in biological and environmental samples often does not exceed 5% of the detected chemical features. Our aim was to develop a computational pipeline that leverages data from HRMS but also incorporates physicochemical properties (equilibrium partition ratios between organic solvents and water; Ksolvent–water) and can propose molecular structures for detected chemical features. As these physicochemical properties are often sufficiently different across isomers, when put together, they can form a unique profile for each isomer, which we describe as the “physicochemical fingerprint”. In our study, we used a comprehensive database of compounds that have been previously reported in human blood and collected their Ksolvent–water values for 129 partitioning systems. We used RDKit to calculate the number of RDKit fragments and the number of RDKit bits per molecule. We then developed and trained an artificial neural network, which used as an input the physicochemical fingerprint of a chemical feature and predicted the number and types of RDKit fragments and RDKit bits present in that structure. These were then used to search the database and propose chemical structures. The average success rate of predicting the right chemical structure ranged from 60 to 86% for the training set and from 48 to 81% for the testing set. These observations suggest that physicochemical fingerprints can assist in the identification of compounds with NTA and substantially improve the number of identified compounds.
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- Linderholm, Linda, et al.
(författare)
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Maternal and cord serum exposure to PCB and DDE methyl sulfone metabolites in eastern Slovakia
- 2007
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 69:3, s. 403-410
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Tidskriftsartikel (refereegranskat)abstract
- Polychlorinated biphenyls (PCBs) were commercially produced between 1959 and 1984 in eastern Slovakia. Improper handling led to a highly contaminated local environment and high levels of PCBs in humans and wildlife in the Michalovce area. The aim of this study was to analyse serum for methylsulfonyl metabolites of PCB (MeSO2-PCBs) and DDE (3-MeSO2-DDE) in serum samples from pregnant women and in a selected number of paired cord blood samples to assess maternal sulfone levels and patterns, and transplacental transfer of these metabolites. The donating women were from two districts in eastern Slovakia. A liquid–liquid extraction method together with separation of substance groups and further clean-up on silica gel columns were applied prior to analysis by gas chromatography/mass spectrometry. 3-MeSO2-DDE was the major methyl sulfone in most of the samples followed by a yet not identified MeSO2-hexaCB, 4′-MeSO2-CB101, 4′-MeSO2-CB87 and 4-MeSO2-CB149. The women from the contaminated area had three times higher concentrations of the MeSO2-PCBs than women from the reference area. This is the first report on methyl sulfone metabolites of PCB and DDE in human cord serum. It is shown that these metabolites are transported through the placenta. The levels of MeSO2-PCBs in the maternal serum were about 1.5 times higher than in the corresponding cord serum on a lipid weight basis. For 3-MeSO2-DDE, the levels were about the same in maternal and cord serum. The difference in the maternal:cord ratio, comparing MeSO2-PCBs with 3-MeSO2-DDE might be due to differences in transport through the placenta caused by their different affinities for lipoproteins and plasma proteins.
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- Zota, Ami R., et al.
(författare)
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Polybrominated diphenyl ethers (PBDEs) and hydroxylated PBDE metabolites (OH-PBDEs) in maternal and fetal tissues, and associations with fetal cytochrome P450 gene expression
- 2018
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 112, s. 269-278
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Human fetal exposures to polybrominated diphenyl ethers (PBDEs) and their metabolites (OH-PBDEs) are unique from adults, and in combination with a different metabolic profile, may make fetal development more sensitive to adverse health outcomes from these exposures. However, we lack data to characterize human fetal PBDE exposures and the metabolic factors that can influence these exposures.OBJECTIVE: We examined differences between 2nd trimester maternal and fetal exposures to PBDEs and OH-PBDEs. We also characterized fetal cytochrome P450 (CYP) mRNA expression and its associations with PBDE exposures.METHODS: We collected paired samples of maternal serum and fetal liver (n=86) with a subset having matched placenta (n=50). We measured PBDEs, OH-PBDEs, and mRNA expression of CYP genes (e.g. CYP1A1, -2E1, -2J2, -2C9) in all samples. As a sensitivity analysis, we measured PBDEs and OH-PBDEs in umbilical cord serum from a subset (n=22).RESULTS: BDE-47 was detected in ≥96% of all tissues. Unadjusted ∑PBDEs concentrations were highest in fetal liver (geometric mean (GM)=0.72ng/g), whereas lipid-adjusted concentrations were highest in cord serum (111.12ng/g lipid). In both cases, fetal concentrations were approximately two times higher than maternal serum levels (GM=0.33ng/g or 48.75ng/g lipid). ΣOH-PBDEs were highest in maternal and cord sera and 20-200 times lower than PBDE concentrations. In regression models, maternal BDE-47 explained more of the model variance of liver than of placenta BDE-47 concentrations (adjusted R2=0.79 vs 0.48, respectively). In adjusted logistic regression models, ∑PBDEs were positively associated with expression of CYP2E1 and -2J2 (placenta), and -1A1 (liver) (p<0.05).CONCLUSION: Our findings suggest that under normal conditions of mid-gestation, the human fetus is directly exposed to concentrations of PBDEs that may be higher than previously estimated based on maternal serum and that these exposures are associated with the expression of mRNAs coding for CYP enzymes. These results will help frame and interpret findings from studies that use maternal or cord blood as proxy measures of fetal exposures, and will inform the molecular pathways by which PBDEs affect human health.
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- Zota, Ami R., et al.
(författare)
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Temporal comparison of PBDEs, OH-PBDEs, PCBs, and OH-PCBs in the serum of second trimester pregnant women recruited from San Francisco General Hospital, California
- 2013
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 47:20, s. 11776-11784
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Tidskriftsartikel (refereegranskat)abstract
- Prenatal exposures to polybrominated diphenyl ethers (PBDEs) can harm neurodevelopment in humans and animals. In 2003-2004, PentaBDE and OctaBDE were banned in California and phased-out of US production; resulting impacts on human exposures are unknown. We previously reported that median serum concentrations of PBDEs and their metabolites (OH-PBDEs) among second trimester pregnant women recruited from San Francisco General Hospital (2008-2009; n = 25) were the highest among pregnant women worldwide. We recruited another cohort from the same clinic in 2011-2012 (n = 36) and now compare serum concentrations of PBDEs, OH-PBDEs, polychlorinated biphenyl ethers (PCBs) (structurally similar compounds banned in 1979), and OH-PCBs between two demographically similar cohorts. Between 2008-2009 and 2011-2012, adjusted least-squares geometric mean (LSGM) concentrations of ∑PBDEs decreased 65% (95% CI: 18, 130) from 90.0 ng/g lipid (95% CI: 64.7, 125.2) to 54.6 ng/g lipid (95% CI: 39.2, 76.2) (p = 0.004); ∑OH-PBDEs decreased 6-fold (p < 0.0001); and BDE-47, -99, and -100 declined more than BDE-153. There was a modest, nonsignificant (p = 0.13) decline in LSGM concentrations of ∑PCBs and minimal differences in ∑OH-PCBs between 2008-2009 and 2011-2012. PBDE exposures are likely declining due to regulatory action, but the relative stability in PCB exposures suggests PBDE exposures may eventually plateau and persist for decades.
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