Global profiling of xenobiotics in human matrices in an untargeted mode is gaining attention for studying the environmental chemical space of the human exposome. Defined as the study of a ...comprehensive inclusion of environmental influences and associated biological responses, human exposome science is currently evolving out of the metabolomics science. In analogy to the latter, the development and applications of high resolution mass spectrometry (HRMS) has shown potential and promise to greatly expand our ability to capture the broad spectrum of environmental chemicals in exposome studies. HRMS can perform both untargeted and targeted analysis because of its capability of full- and/or tandem-mass spectrum acquisition at high mass accuracy with good sensitivity. The collected data from target, suspect and non-target screening can be used not only for the identification of environmental chemical contaminants in human matrices prospectively but also retrospectively. This review covers recent trends and advances in this field. We focus on advances and applications of HRMS in human biomonitoring studies, and data acquisition and mining. The acquired insights provide stepping stones to improve understanding of the human exposome by applying HRMS, and the challenges and prospects for future research.
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•Human biomonitoring is limited by the number of chemicals analyzed in a targeted approach.•High resolution mass spectrometry (HRMS) can monitor a broad-spectrum of exposure and biological response markers.•Advances in data acquisition workflows accelerate untargeted profiling of the human exposome environmental chemical space.•Intelligent data mining filters and tools are constantly evolving to characterize unknown compounds.•High throughput simultaneous identification and quantitation of new chemicals and metabolites will be feasible with HRMS.
Genetic and environmental factors contribute to the etiologies of autism spectrum disorder (ASD), but evidence of specific environmental exposures and susceptibility windows is limited. Here we study ...monozygotic and dizygotic twins discordant for ASD to test whether fetal and postnatal metal dysregulation increases ASD risk. Using validated tooth-matrix biomarkers, we estimate pre- and post-natal exposure profiles of essential and toxic elements. Significant divergences are apparent in metal uptake between ASD cases and their control siblings, but only during discrete developmental periods. Cases have reduced uptake of essential elements manganese and zinc, and higher uptake of the neurotoxin lead. Manganese and lead are also correlated with ASD severity and autistic traits. Our study suggests that metal toxicant uptake and essential element deficiency during specific developmental windows increases ASD risk and severity, supporting the hypothesis of systemic elemental dysregulation in ASD. Independent replication in population-based studies is needed to extend these findings.
Lead (Pb) is a potent neurotoxicant with no safe level of exposure. Elevated levels of Pb and arsenic (As) are found in the air and soil near facilities that recycle lead-acid batteries in the United ...States. In urban Los Angeles County, California, a facility processed ∼11 million batteries per year and operated for decades without proper environmental review. Measuring Pb and As in shed deciduous teeth is a promising technique to assess prenatal and early life exposure. In this pilot study coined the “Truth Fairy” Project, 50 shed deciduous teeth from 43 children living their entire lives within 2 miles of the smelter were analyzed to understand retrospective exposure to toxic metals using a community-driven research approach. Concentrations of Pb and As in teeth were assessed using laser-ablation-inductively coupled plasma-mass spectrometry. Soil Pb concentrations were determined using spatial kriging of surface soil measurements. The mean prenatal calcium normalized Pb levels in teeth samples (reported as a ratio 208Pb:43Ca) was 4.104 × 10–4 (SD 4.123 × 10–4), and the mean postnatal 208Pb:43Ca level was 4.109 × 10–4 (SD 3.369 × 10–4). Adjusted for maternal education and batch, we observe positive significant relationship between prenatal teeth Pb per 100 ppm increase in soil Pb (β = 3.48, 95% CI 1.11, 5.86). The Truth Fairy study suggests prenatal and early life exposure to toxic metals is associated with legacy soil contamination in an urban community near a smelter.
Metal exposure alters neurodevelopmental outcomes; little is known about critical windows of susceptibility when exposure exerts the strongest effect.
To examine associations between dentine ...biomarkers of manganese (Mn), zinc (Zn) and lead (Pb) and later childhood behaviors.
Subjects enrolled in a longitudinal birth cohort study in Mexico City provided naturally shed deciduous teeth. We estimated weekly prenatal and postnatal dentine Mn, Zn and Pb concentrations in teeth using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) and measured behavior at ages 8–11 years of age using the Behavior Assessment System for Children, 2nd edition (BASC-2). We used distributed lag models and lagged weighted quantile sum regression to identify the role of individual and combined dentine biomarkers of Mn, Zn and Pb on behavioral outcomes controlling for maternal education and gestational age.
Among the 133 subjects included in this study, prenatal and early postnatal dentine Mn appeared protective against childhood behavioral problems, specifically hyperactivity and attention. Postnatal dentine Mn was associated with increased reporting of internalizing problems, specifically anxiety. At 6 months, a 1-unit increase (unit = 1 SD of log concentration) in Mn was associated with a 0.18-unit (unit = 1 SD of BASC-2 score) increase in internalizing symptoms score and a 0.25-unit increase in anxiety. Postnatal Pb was associated with increasing anxiety symptoms; at 12 months, a 1-unit increase in Pb was associated with a 0.4 unit increase in anxiety symptoms. When examined as a metal mixture, we observed two potential windows of susceptibility to increased anxiety symptoms: the first window (0–8 months) appeared driven by Mn, the second window (8–12 months) was driven by the metal mixture and dominated by Pb. A 1-unit increase in the mixture index was associated with a 0.7-unit increase in SD of anxiety symptoms.
Childhood behaviors may demonstrate postnatal windows of susceptibility to individual and mixed metal concentrations measured in deciduous teeth. Prenatal dentine Mn may be protective, while excessive early postnatal Mn may increase risk for adverse behaviors. In combination, higher concentrations of Mn, Zn and Pb may have an adverse impact on behavior.
•Tooth-matrix biomarkers were used to identify windows of susceptibility to Mn, Zn, and Pb.•Prenatal and early postnatal Mn appears protective against externalizing behavior.•Postnatal Mn is associated with higher internalizing behaviors, especially anxiety.•Co-exposure to Mn, Zn and Pb at 12 months is associated with anxiety.
We investigate the role of the mitochondrion, an organelle highly sensitive to environmental agents, in the influence of prenatal air pollution exposure on neurodevelopment and behavior in 96 ...children with autism spectrum disorder (ASD) 45 with neurodevelopmental regression (NDR); 76% Male; mean (SD) age 10 y 9 m (3 y 9 m). Mitochondrial function was assessed using the Seahorse XFe96 in fresh peripheral blood mononuclear cells. Second and third trimester average and maximal daily exposure to fine air particulate matter of diameter ≤2.5 µm (PM
) was obtained from the Environmental Protection Agency's Air Quality System. Neurodevelopment was measured using the Vineland Adaptive Behavior Scale 2nd edition and behavior was assessed using the Aberrant Behavior Checklist and Social Responsiveness Scale. Prenatal PM
exposure influenced mitochondrial respiration during childhood, but this relationship was different for those with (r = 0.25-0.40) and without (r = -0.07 to -0.19) NDR. Mediation analysis found that mitochondrial respiration linked to energy production accounted for 25% (SD = 2%) and 10% (SD = 2%) of the effect of average prenatal PM
exposure on neurodevelopment and behavioral symptoms, respectively. Structural equation models estimated that PM
and mitochondrial respiration accounted for 34% (SD = 4%) and 36% (SD = 3%) of the effect on neurodevelopment, respectively, and that behavior was indirectly influenced by mitochondrial respiration through neurodevelopment but directly influenced by prenatal PM
. Our results suggest that prenatal exposure to PM
disrupts neurodevelopment and behavior through complex mechanisms, including long-term changes in mitochondrial respiration and that patterns of early development need to be considered when studying the influence of environmental agents on neurodevelopmental outcomes.
Early-life dietary transitions reflect fundamental aspects of primate evolution and are important determinants of health in contemporary human populations. Weaning is critical to developmental and ...reproductive rates; early weaning can have detrimental health effects but enables shorter inter-birth intervals, which influences population growth. Uncovering early-life dietary history in fossils is hampered by the absence of prospectively validated biomarkers that are not modified during fossilization. Here we show that large dietary shifts in early life manifest as compositional variations in dental tissues. Teeth from human children and captive macaques, with prospectively recorded diet histories, demonstrate that barium (Ba) distributions accurately reflect dietary transitions from the introduction of mother's milk through the weaning process. We also document dietary transitions in a Middle Palaeolithic juvenile Neanderthal, which shows a pattern of exclusive breastfeeding for seven months, followed by seven months of supplementation. After this point, Ba levels in enamel returned to baseline prenatal levels, indicating an abrupt cessation of breastfeeding at 1.2 years of age. Integration of Ba spatial distributions and histological mapping of tooth formation enables novel studies of the evolution of human life history, dietary ontogeny in wild primates, and human health investigations through accurate reconstructions of breastfeeding history.
Surface-attached nanobubbles once formed and kept under constant conditions show remarkable stability against dissolution. When observing a large population of nanobubbles using total internal ...reflection fluorescence (TIRF) microscopy, we find rare events of coalescence, i.e., the merging of two neighboring bubbles. The new bubble covers the convex hull of their “footprint”, with most of the three-phase contact line remaining pinned. Interestingly, the newly formed bubble is not shape-stable but grows in height within several 100 ms. This growth dynamic can be described with the classical diffusion theory using contact line pinning and Henry’s law. This theory also shows that surface nanobubbles can attain a stable shape with a contact angle larger than 90° in supersaturated liquid.
The fluid dynamic interaction of cavitation bubbles with adherent cells on a substrate is experimentally investigated. We find that the nonspherical collapse of bubbles near to the boundary is ...responsible for cell detachment. High-speed photography reveals that a wall bounded flow leads to the detachment of cells. Cells at the edge of the circular area of detachment are found to be permanently porated, whereas cells at some distance from the detachment area undergo viable cell membrane poration (sonoporation). The wall flow field leading to cell detachment is modeled with a self-similar solution for a wall jet, together with a kinetic ansatz of adhesive bond rupture. The self-similar solution for the
δ-type wall jet compares very well with the full solution of the Navier-Stokes equation for a jet of finite thickness. Apart from annular sites of sonoporation we also find more homogenous patterns of molecule delivery with no cell detachment.
The exposome concept proposes a comprehensive assessment of environmental exposures from the prenatal period onwards. However, determining exposure timing, especially over the prenatal period, is a ...major challenge in environmental epidemiologic studies.
For decades, teeth have been used to estimate long-term cumulative exposure to metals. Recently developed high-dimensional analytical methods, which combine sophisticated histological and chemical analysis to precisely sample tooth layers that correspond to specific life stages, have the potential to reconstruct the exposome in the second and third trimesters of prenatal development and during early childhood.
A retrospective temporal exposomic approach that precisely measures exposure intensity 'and timing' during prenatal and early childhood development would substantially aid epidemiologic investigations, particularly case-control studies of rare health outcomes.
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