Search

Background: Prenatal alcohol exposure (PAE), leading to fetal alcohol spectrum disorders (FASD), is a serious public health issue in the United States and globally. Diagnosis of FASD is crucial in obtaining appropriate care, but it is not always possible when PAE cannot be documented. Methods: Deciduous teeth from a child with known PAE and a child with known absence of PAE were analyzed using liquid chromatography‐isotope dilution tandem mass spectrometry (LC‐IDMS/MS) in a multiple‐reaction monitoring mode for direct markers and LC‐high resolution MS in positive and negative mode with hydrophilic interaction liquid chromatography and reverse‐phase chromatography, respectively, for indirect markers. Results: Direct markers of PAE (ethyl glucuronide and ethyl sulfate) were detected in prenatal and postnatal dentine from a case tooth but not from a control tooth. Indirect biomarker analysis indicated a dysregulation of amino acids and an increase in cholesterol sulfate in the case compared to the control tooth. Conclusions: This proof‐of‐concept study demonstrates for the first time that direct biomarkers of PAE are detectable and measurable in deciduous teeth which begin forming in utero and are typically naturally shed between 5 and 12 years of age. Further examination of these novel biomarkers may allow diagnosis of FASD where documentation of PAE is otherwise unavailable. Furthermore, because teeth grow incrementally, defined growth zones can be sampled allowing for identification of gestational timing of PAE to help better understand mechanisms underlying alcohol's disruption of perinatal development. [ABSTRACT FROM AUTHOR]

Rationale: Organophosphate flame retardants (OPFRs) are a class of flame retardants widely found in environmental and biological matrices that have been extensively studied due to their adverse health effects in humans. OPFRs are loosely bound chemicals that can detach from treated products and be released into indoor and outdoor environments, where they have the potential to further undergo transformation and degradation processes, in particular the chlorinated OPFRs (Cl‐PFRs). Their detection remains a moving target for analysts, and traditional targeted mass spectrometry methods are suitable only for those compounds with authentic standards. Methods: Mass defect filter (MDF) is a strategy to filter molecular features using thresholds applied to the mass defect value of a target ion or molecular feature of interest. We have developed an MDF strategy for the detection and tentative identification of twelve potential Cl‐PFR transformation products in a study mixture of six known Cl‐PFRs using MS/MS data acquired on a high‐resolution mass spectrometer. Most compounds in the Cl‐PFRs family share a ClO4P group as a core structure, of which modification results in a significant shift in the exact masses of the resulting compounds but show only a minimal shift in their mass defects. Subsequently, the MDF strategy was employed to tentatively identify Cl‐PFRs retrospectively in six human urine samples that had previously been analyzed. Results: MDF in combination with product ion filtering for the characteristic [H2O3P]+ and [H4O4P]+ ions and neutral loss filtering for the characteristic CnH2n‐xClx group resulted in revealing suspects and homologues in the Cl‐PFRs family. Furthermore, the MDF of the product ions detected additional Cl‐PFR‐related compounds that differed significantly in the exact masses of both precursor and product ions but had minimal shift in the mass defects of product ions. The mass defect of one or more common product ions helped to detect a few Cl‐PFR analogs that had not been identified by MDF of the core structure precursor ion. Conclusions: MDF helped to detect some Cl‐PFRs present in lower concentrations, which went undetected without data filters. MDF also helped to detect chromatographic peaks for Cl‐PFR homologues that are likely structural analogs that resulted from impurities and/or derivatives and transformation products. The methodology was applied to demonstrate and tentatively detect known and suspect Cl‐PFRs in human urine samples retrospectively. [ABSTRACT FROM AUTHOR]

Human biomonitoring studies for water contaminants are often accompanied by surveys relying solely on total drinking water consumption rates, thus, failing to account for specific water sources (bottled and tap water) and use habits, such as water used for preparing cold/hot beverages (coffee, tea, juice, etc.). Despite the extensive use of bisphenol A (BPA) in polycarbonate (PC)-based water contact materials, rarely do BPA biomonitoring studies focus on various PC water uses and sources. Better resolved water consumption rates could reduce the uncertainty associated with surrogate daily BPA intake estimates using fine-tuned surveys. This approach provided a proof of concept on inclusion of water consumption from various sources and uses into estimates of daily intake for water contaminants like BPA found in water-contact materials. The next steps would be in quantifying the extent of improvement in exposure assessment that adds value to refined survey designs. [ABSTRACT FROM AUTHOR]

Objective: We previously found that per- and polyfluoroalkyl substances (PFAS) mixture exposure is inversely associated with SARS-CoV-2 IgG (IgG) antibody levels in pregnant individuals. Here, we aim to identify metabolites mediating this relationship to elucidate the underlying biological pathways., Methods: We included 59 pregnant participants from a US-based pregnancy cohort. Untargeted metabolomic profiling was performed using Liquid Chromatography-High Resolution Sass spectrometry (LC-HRMS), and weighted Quantile Sum (WQS) regression was applied to assess the PFAS and metabolites mixture effects on IgG. Metabolite indices positively or negatively associated with IgG levels were constructed separately and their mediation effects were examined independently and jointly., Results: The PFAS-index was negatively associated with IgG levels (beta=-0.273, p=0.002), with PFHpS and PFHxS as major contributors. Two metabolite-indices were constructed, one positively (beta=1.260, p<0.001) and one negatively (beta=-0.997, p<0.001) associated with IgG. Key contributors for these indices included protoporphyrin, 5-hydroxytryptophan, n-acetylproline, and tyrosine. Analysis of single mediator showed that 48.9% (95%CI: 21.9%,125.0%) and 50.1% (95% CI: 8.1%, 90.1%) of the PFAS index-IgG total effect were mediated by the negative and positive metabolite-indices, respectively. Joint analysis of the metabolite-indices indicated a cumulative mediation effect of 73.6% (95%CI: 44.9%, 116.4%). Enriched pathways associated with these metabolites indices were phenylalanine, tyrosine, and tryptophan biosynthesis and arginine metabolism., Conclusions: We observed significant mediation effects of plasma metabolites on the PFAS-IgG relationship, suggesting that PFAS disrupts the balance of plasma metabolites that contributes to reduced plasma IgG production.

Background and Aims: Scarce knowledge about the impact of metabolism-disrupting chemicals (MDCs) on liver injury limits opportunities for intervention. We evaluated pregnancy MDC-mixture associations with liver injury and effect modification by folic acid (FA) supplementation in mother-child pairs., Methods: We studied ∼200 mother-child pairs from the Mexican PROGRESS cohort, with measured 43 MDCs during pregnancy (estimated air pollutants, blood/urine metals or metalloids, urine high- and low-molecular-weight phthalate [HMWPs, LMWPs] and organophosphate-pesticide [OP] metabolites), and serum liver enzymes (ALT, AST) at ∼9 years post-parturition. We defined liver injury as elevated liver enzymes in children, and using established clinical scores for steatosis and fibrosis in mothers (i.e., AST:ALT, FLI, HSI, FIB-4). Bayesian Weighted Quantile Sum regression assessed MDC-mixture associations with liver injury outcomes. We further examined chemical-chemical interactions and effect modification by self-reported FA supplementation., Results: In children, many MDC-mixtures were associated with liver injury outcomes. Per quartile HMWP-mixture increase, ALT increased by 10.1% (95%CI: 1.67%, 19.4%) and AST by 5.27% (95% CI: 0.80%, 10.1%). LMWP-mixtures and air pollutant-mixtures were associated with higher AST and ALT, respectively. Air pollutant and non-essential metal/element associations with liver enzymes were attenuated by maternal cobalt blood concentrations ( p -interactions<0.05). In mothers, only the LMWP-mixture was associated with liver injury [OR=1.53 (95%CI: 1.01, 2.28) for HSI>36, and OR=1.62 (95%CI: 1.05, 2.49) for AST:ALT<1]. In mothers and children, most associations were attenuated (null) at FA supplementation≥600mcg/day ( p -interactions<0.05)., Conclusions: Pregnancy MDC exposures may increase liver injury risk, particularly in children. These associations may be attenuated by higher FA supplementation and maternal cobalt levels.