High-Resolution Mass Spectrometry for Human Exposomics: Expanding Chemical Space Coverage.

In the modern "omics" era, measurement of the human exposome is a critical missing link between genetic drivers and disease outcomes. High-resolution mass spectrometry (HRMS), routinely used in proteomics and metabolomics, has emerged as a leading technology to broadly profile chemical exposure agents and related biomolecules for accurate mass measurement, high sensitivity, rapid data acquisition, and increased resolution of chemical space. Non-targeted approaches are increasingly accessible, supporting a shift from conventional hypothesis-driven, quantitation-centric targeted analyses toward data-driven, hypothesis-generating chemical exposome-wide profiling. However, HRMS-based exposomics encounters unique challenges. New analytical and computational infrastructures are needed to expand the analysis coverage through streamlined, scalable, and harmonized workflows and data pipelines that permit longitudinal chemical exposome tracking, retrospective validation, and multi-omics integration for meaningful health-oriented inferences. In this article, we survey the literature on state-of-the-art HRMS-based technologies, review current analytical workflows and informatic pipelines, and provide an up-to-date reference on exposomic approaches for chemists, toxicologists, epidemiologists, care providers, and stakeholders in health sciences and medicine. We propose efforts to benchmark fit-for-purpose platforms for expanding coverage of chemical space, including gas/liquid chromatography-HRMS (GC-HRMS and LC-HRMS), and discuss opportunities, challenges, and strategies to advance the burgeoning field of the exposome.

Association between Personal Abiotic Airborne Exposures and Body Composition Changes among Healthy Adults (60-69 Years Old): A Combined Exposome-Wide and Lipidome Mediation Approach from the China BAPE Study.

BACKGROUND: Evidence suggested that abiotic airborne exposures may be associated with changes in body composition. However, more evidence is needed to identify key pollutants linked to adverse health effects and their underlying biomolecular mechanisms, particularly in sensitive older adults. OBJECTIVES: Our research aimed to systematically assess the relationship between abiotic airborne exposures and changes in body composition among healthy older adults, as well as the potential mediating mechanisms through the serum lipidome. METHODS: From September 2018 to January 2019, we conducted a monthly survey among 76 healthy adults (60-69 years old) in the China Biomarkers of Air Pollutant Exposure (BAPE) study, measuring their personal exposures to 632 abiotic airborne pollutions using MicroPEM and the Fresh Air wristband, 18 body composition indicators from the InBody 770 device, and lipidomics from venous blood samples. We used an exposome-wide association study (ExWAS) and deletion/substitution/addition (DSA) model to unravel complex associations between exposure to contaminant mixtures and body composition, a Bayesian kernel machine regression (BKMR) model to assess the overall effect of key exposures on body composition, and mediation analysis to identify lipid intermediators. RESULTS: The ExWAS and DSA model identified that 2,4,5-T methyl ester (2,4,5-TME), 9,10-Anthracenedione (ATQ), 4b,8-dimethyl-2-isopropylphenanthrene, and 4b,5,6,7,8,8a,9,10-octahydro-(DMIP) were associated with increased body fat mass (BFM), fat mass indicators (FMI), percent body fat (PBF), and visceral fat area (VFA) in healthy older adults [Bonferroni-Hochberg false discovery rate (FDRBH)<0.05]. The BKMR model demonstrated a positive correlation between contaminants (anthracene, ATQ, copaene, di-epi-α-cedrene, and DMIP) with VFA. Mediation analysis revealed that phosphatidylcholine [PC, PC(16:1e/18:1), PC(16:2e/18:0)] and sphingolipid [SM, SM(d18:2/24:1)] mediated a significant portion, ranging from 12.27% to 26.03% (p-value <0.05), of the observed increase in VFA. DISCUSSION: Based on the evidence from multiple model results, ATQ and DMIP were statistically significantly associated with the increased VFA levels of healthy older adults, potentially regulated through lipid intermediators. These findings may have important implications for identifying potentially harmful environmental chemicals and developing targeted strategies for the control and prevention of chronic diseases in the future, particularly as the global population is rapidly aging. https://doi.org/10.1289/EHP13865.

Personal exposure to airborne organic pollutants and lung function changes among healthy older adults.

Epidemiological evidence on the impact of airborne organic pollutants on lung function among the elderly is limited, and their underlying biological mechanisms remain largely unexplored. Herein, a longitudinal panel study was conducted in Jinan, Shandong Province, China, involving 76 healthy older adults monitored over a span of five months repetitively. We systematically evaluated personal exposure to a diverse range of airborne organic pollutants using a wearable passive sampler and their effects on lung function. Participants' pulmonary function indicators were assessed, complemented by comprehensive multi-omics analyses of blood and urine samples. Leveraging the power of interaction analysis, causal inference test (CIT), and integrative pathway analysis (IPA), we explored intricate relationships between specific organic pollutants, biomolecules, and lung function deterioration, elucidating the biological mechanisms underpinning the adverse impacts of these pollutants. We observed that bis (2-chloro-1-methylethyl) ether (BCIE) was significantly associated with negative changes in the forced vital capacity (FVC), with glycerolipids mitigating this adverse effect. Additionally, 31 canonical pathways [e.g., high mobility group box 1 (HMGB1) signaling, phosphatidylinositol 3-kinase (PI3K)/AKT pathway, epithelial mesenchymal transition, and heme and nicotinamide adenine dinucleotide (NAD) biosynthesis] were identified as potential mechanisms. These findings may hold significant implications for developing effective strategies to prevent and mitigate respiratory health risks arising from exposure to such airborne pollutants. However, due to certain limitations of the study, our results should be interpreted with caution.

Assessment of wood smoke induced pulmonary toxicity in normal- and chronic bronchitis-like bronchial and alveolar lung mucosa models at air-liquid interface.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has the highest increased risk due to household air pollution arising from biomass fuel burning. However, knowledge on COPD patho-mechanisms is mainly limited to tobacco smoke exposure. In this study, a repeated direct wood smoke (WS) exposure was performed using normal- (bro-ALI) and chronic bronchitis-like bronchial (bro-ALI-CB), and alveolar (alv-ALI) lung mucosa models at air-liquid interface (ALI) to assess broad toxicological end points. METHODS: The bro-ALI and bro-ALI-CB models were developed using human primary bronchial epithelial cells and the alv-ALI model was developed using a representative type-II pneumocyte cell line. The lung models were exposed to WS (10 min/exposure; 5-exposures over 3-days; n = 6-7 independent experiments). Sham exposed samples served as control. WS composition was analyzed following passive sampling. Cytotoxicity, total cellular reactive oxygen species (ROS) and stress responsive NFkB were assessed by flow cytometry. WS exposure induced changes in gene expression were evaluated by RNA-seq (p ≤ 0.01) followed by pathway enrichment analysis. Secreted levels of proinflammatory cytokines were assessed in the basal media. Non-parametric statistical analysis was performed. RESULTS: 147 unique compounds were annotated in WS of which 42 compounds have inhalation toxicity (9 very high). WS exposure resulted in significantly increased ROS in bro-ALI (11.2%) and bro-ALI-CB (25.7%) along with correspondingly increased NFkB levels (bro-ALI: 35.6%; bro-ALI-CB: 18.1%). A total of 1262 (817-up and 445-down), 329 (141-up and 188-down), and 102 (33-up and 69-down) genes were differentially regulated in the WS-exposed bro-ALI, bro-ALI-CB, and alv-ALI models respectively. The enriched pathways included the terms acute phase response, mitochondrial dysfunction, inflammation, oxidative stress, NFkB, ROS, xenobiotic metabolism of AHR, and chronic respiratory disorder. The enrichment of the 'cilium' related genes was predominant in the WS-exposed bro-ALI (180-up and 7-down). The pathways primary ciliary dyskinesia, ciliopathy, and ciliary movement were enriched in both WS-exposed bro-ALI and bro-ALI-CB. Interleukin-6 and tumor necrosis factor-α were reduced (p < 0.05) in WS-exposed bro-ALI and bro-ALI-CB. CONCLUSION: Findings of this study indicate differential response to WS-exposure in different lung regions and in chronic bronchitis, a condition commonly associated with COPD. Further, the data suggests ciliopathy as a candidate pathway in relation to WS-exposure.

Per- and polyfluoroalkyl substances (PFAS) and thyroid hormone measurements in dried blood spots and neonatal characteristics: a pilot study.

BACKGROUND: Pediatric thyroid diseases have been increasing in recent years. Environmental risk factors such as exposures to chemical contaminants may play a role but are largely unexplored. Archived neonatal dried blood spots (DBS) offer an innovative approach to investigate environmental exposures and effects. OBJECTIVE: In this pilot study, we applied a new method for quantifying per- and polyfluoroalkyl substances (PFAS) to 18 archived DBS from babies born in California from 1985-2018 and acquired thyroid hormone measurements from newborn screening tests. Leveraging these novel data, we evaluated (1) changes in the concentrations of eight PFAS over time and (2) the relationship between PFAS concentrations, thyroid hormone concentrations, and neonatal characteristics to inform future research. METHODS: PFAS concentrations in DBS were measured using ultra-high-performance liquid chromatography-mass spectrometry. Summary statistics and non-parametric Wilcoxon rank-sum and Kruskal-Wallis tests were used to evaluate temporal changes in PFAS concentrations and relationships between PFAS concentrations, thyroid hormone concentrations, and neonatal characteristics. RESULTS: The concentration and detection frequencies of several PFAS (PFOA, PFOS, and PFOSA) declined over the assessment period. We observed that the timing of specimen collection in hours after birth was related to thyroid hormone but not PFAS concentrations, and that thyroid hormones were related to some PFAS concentrations (PFOA and PFOS). IMPACT STATEMENT: This pilot study examines the relationship between concentrations of eight per- and polyfluoroalkyl substances (PFAS), thyroid hormone levels, and neonatal characteristics in newborn dried blood spots (DBS) collected over a period of 33 years. To our knowledge, 6 of the 22 PFAS we attempted to measure have not been quantified previously in neonatal DBS, and this is the first study to examine both PFAS and thyroid hormone concentrations using DBS. This research demonstrates the feasibility of using newborn DBS for quantifying PFAS exposures in population-based studies, highlights methodological considerations in the use of thyroid hormone data for future studies using newborn DBS, and indicates potential relationships between PFAS concentrations and thyroid hormones for follow-up in future research.

Aquatic Vegetation, an Understudied Depot for PFAS.

Per- and polyfluoroalkyl substances (PFAS) are a class of manufactured chemicals that have been extensively utilized worldwide. We hypothesize that the presence, uptake, and accumulation of PFAS in aquatic vegetation (AV) is dependent upon several factors, such as the physiochemical properties of PFAS and proximity to potential sources. In this study, AV was collected from eight locations in Florida to investigate the PFAS presence, accumulation, and spatiotemporal distribution. PFAS were detected in AV at all sampling locations, with a range from 0.18 to 55 ng/g sum (∑)PFAS. Individual PFAS and their concentrations varied by sampling location, time, and AV species. A total of 12 PFAS were identified, with the greatest concentrations measured in macroalgae. The average bioconcentration factor (BCF) among all samples was 1225, indicating high PFAS accumulation in AV from surface water. The highest concentrations, across all AV types, were recorded in the Indian River Lagoon (IRL), a location with a history of elevated PFAS burdens. The present study represents the first investigation of PFAS in naturally existing estuarine AV, filling an important gap on PFAS partitioning within the environment, as well as providing insights into exposure pathways for aquatic herbivores. Examining the presence, fate, and transport of these persistent chemicals in Florida's waterways is critical for understanding their effect on environmental, wildlife, and human health.

Adequacy of stationary measurements as proxies for residential personal exposure to gaseous and particle air pollutants.

People are exposed to myriad of airborne pollutants in their homes. Owing to diverse potential sources of air pollution and human activity patterns, accurate assessment of residential exposures is complex. In this study, we explored the relationship between personal and stationary air pollutant measurements in residences of 37 participants working from home during the heating season. Stationary environmental monitors (SEMs) were located in the bedroom, living room or home office and personal exposure monitors (PEMs) were worn by the participants. SEMs and PEMs included both real-time sensors and passive samplers. During three consecutive weekdays, continuous data were obtained for particle number concentration (size range 0.3-10 µm), carbon dioxide (CO2), and total volatile organic compounds (TVOC), while passive samplers collected integrated measures of 36 volatile organic compounds (VOCs) and semi volatile organic compounds (SVOCs). The personal cloud effect was detected in >80% of the participants for CO2 and >50% participants for PM10. Multiple linear regression analysis showed that a single CO2 monitor placed in the bedroom efficiently represented personal exposure to CO2 (R2 = 0.90) and moderately so for PM10 (R2 = 0.55). Adding a second or third sensor in a residence did not lead to improved exposure estimates for CO2, with only 6-9% improvement for particles. Selecting data from SEMs when participants were in the same room improved personal exposure estimates by 33% for CO2 and 5% for particles. Out of 36 detected VOCs and SVOCs, 13 had at least 50% higher concentrations in personal versus stationary samples. Findings from this study aid improved understanding of the complex dynamics of gaseous and particle pollutants and their sources in residences, and could support the development of refined procedures for residential air quality monitoring and inhalation exposure assessment.

Trace analysis of per- and polyfluorinated alkyl substances (PFAS) in dried blood spots - Demonstration of reproducibility and comparability to venous blood samples.

Per- and polyfluoroalkyl substances (PFAS) are a group of man-made chemicals that have been widely used in consumer, personal care, and household products for their stain- and water-repellent properties. PFAS exposure has been linked to various adverse health outcomes. Such exposure has commonly been evaluated in venous blood samples. While this sample type can be obtained from healthy adults, a less invasive method of blood collection is required when evaluating vulnerable populations. Dried blood spots (DBS) have gained attention as a biomatrix for exposure assessment given the relative ease of collection, transport, and storage. The objective of this study was to develop and validate an analytical method to measure PFAS in DBS. A workflow is presented for extracting PFAS from DBS, chemical analysis by liquid chromatography-high resolution mass spectrometry, normalization for blood mass, and blank correction to account for potential contamination. Over 80 % recovery was achieved for the 22 PFAS measured with an average coefficient of variation of 14 %. Comparison of PFAS concentrations detected in DBS and paired whole blood samples from six healthy adults was correlated (R2 > 0.9). Findings demonstrate trace levels of a broad range of PFAS in DBS can be reproducibly measured and are comparable to liquid whole blood samples. DBS can offer novel insights to environmental exposures, including during critical windows of susceptibility (i.e., in utero, early life), which have been largely uncharacterized.

Novel perfluoroalkyl substances (PFAS) discovered in whole blood using automated non-targeted analysis of dried blood spots.

A small subset of per- and polyfluoroalkyl substances (PFAS) are routinely screened in human blood. These compounds generally explain <50 % of the total PFAS in human blood. The percentage of known PFAS in human blood has been decreasing as replacement PFAS and more complex PFAS chemistries are introduced to the market. Most of these novel PFAS have not been previously identified. Non-targeted methods are required to characterize this "dark matter" PFAS. Our objective was to apply non-targeted PFAS analysis to human blood to gain an understanding about the sources, concentrations, and toxicity of these compounds. A high-resolution tandem mass spectrometry (HRMS) and software workflow for PFAS characterization in dried blood spots is reported. Dried blood spots are a less invasive collection technique compared to venous blood draws, allowing collection from vulnerable populations. Biorepositories of archived dried blood spots are available internationally from newborns and present opportunities to study prenatal exposure to PFAS. In this study, dried blood spot cards were analyzed using iterative MS/MS by liquid chromatography HRMS. Data processing was conducted using FluoroMatch Suite including a visualizer tool that presents homologous series, retention time vs m/z plots, MS/MS spectra, feature tables, annotations, and fragments for fragment screening. The researcher performing data-processing and annotation was blinded to the fact that standards were spiked in, and was able to annotate 95 % of standards spiked on dried blood spot samples, signifying a low false negative rate using FluoroMatch Suite. A total of 28 PFAS (20 standards and 4 exogenous compounds) were detected across five homologous series with Schymanski Level 2 confidence. Of these 4, 3 were perfluoroalkyl ether carboxylic acids (PFECA), a chemical class of PFAS which is increasingly being detected in environmental and biological matrices but is not currently screened in most targeted analysese. A further 86 potential PFAS were detected using fragment screening. PFAS are extremely persistent and widespread yet remain largely unregulated. Our findings will contribute to an improved an understanding of exposures. Application of these methods in environmental epidemiology studies have the potential to inform policy with regards to PFAS monitoring, regulation, and individual-level mitigation strategies.

Wearable Passive Samplers for Assessing Environmental Exposure to Organic Chemicals: Current Approaches and Future Directions.

PURPOSE OF REVIEW: We are continuously exposed to dynamic mixtures of airborne contaminants that vary by location. Understanding the compositional diversity of these complex mixtures and the levels to which we are each exposed requires comprehensive exposure assessment. This comprehensive analysis is often lacking in population-based studies due to logistic and analytical challenges associated with traditional measurement approaches involving active air sampling and chemical-by-chemical analysis. The objective of this review is to provide an overview of wearable passive samplers as alternative tools to active samplers in environmental health research. The review highlights the advances and challenges in using wearable passive samplers for assessing personal exposure to organic chemicals and further presents a framework to enable quantitative measurements of exposure and expanded use of this monitoring approach to the population scale. RECENT FINDINGS: Overall, wearable passive samplers are promising tools for assessing personal exposure to environmental contaminants, evident by the increased adoption and use of silicone-based devices in recent years. When combined with high throughput chemical analysis, these exposure assessment tools present opportunities for advancing our ability to assess personal exposures to complex mixtures. Most designs of wearable passive samplers used for assessing exposure to semi-volatile organic chemicals are currently uncalibrated, thus, are mostly used for qualitative research. The challenge with using wearable samplers for quantitative exposure assessment mostly lies with the inherent complexity in calibrating these wearable devices. Questions remain regarding how they perform under various conditions and the uncertainty of exposure estimates. As popularity of these samplers grows, it is critical to understand the uptake kinetics of chemicals and the different environmental and meteorological conditions that can introduce variability. Wearable passive samplers enable evaluation of exposure to hundreds of chemicals. The review presents the state-of-the-art of technology for assessing personal exposure to environmental chemicals. As more studies calibrate wearable samplers, these tools present promise for quantitatively assessing exposure at both the individual and population levels.

Characterizing the external exposome using passive samplers-comparative assessment of chemical exposures using different wearable form factors.

BACKGROUND: Organic contaminants are released into the air from building materials/furnishings, personal care, and household products. Wearable passive samplers have emerged as tools to characterize personal chemical exposures. The optimal placement of these samplers on an individual to best capture airborne exposures has yet to be evaluated. OBJECTIVE: To compare personal exposure to airborne contaminants detected using wearable passive air samplers placed at different positions on the body. METHODS: Participants (n = 32) simultaneously wore four passive Fresh Air samplers, on their head, chest, wrist, and foot for 24 hours. Exposure to 56 airborne organic contaminants was evaluated using thermal desorption gas chromatography high resolution mass spectrometry with a targeted data analysis approach. RESULTS: Distinct exposure patterns were detected by samplers positioned on different parts of the body. Chest and wrist samplers were the most similar with correlations identified for 20% of chemical exposures (Spearman's Rho > 0.8, p < 0.05). In contrast, the greatest differences were found for head and foot samplers with the weakest correlations across evaluated exposures (8% compounds, Spearman's Rho > 0.8, p < 0.05). SIGNIFICANCE: The placement of wearable passive air samplers influences the exposures captured and should be considered in future exposure and epidemiological studies. IMPACT STATEMENT: Traditional approaches for assessing personal exposure to airborne contaminants with active samplers presents challenges due to their cost, size, and weight. Wearable passive samplers have recently emerged as a non-invasive, lower cost tool for measuring environmental exposures. While these samplers can be worn on different parts of the body, their position can influence the type of exposure that is captured. This study comprehensively evaluates the exposure to airborne chemical contaminants measured at different passive sampler positions worn on the head, chest, wrist, and foot. Findings provide guidance on sampler placement based on chemicals and emission sources of interest.

Hemoglobin normalization outperforms other methods for standardizing dried blood spot metabolomics: A comparative study.

Dried blood spot (DBS) metabolomics has numerous applications in newborn health screening, exposomics, and biomonitoring of environmental chemicals in pregnant women and the elderly. However, accurate metabolite quantification is hindered by several challenges: notably the "hematocrit effect" and unknown blood-spotting volumes. Different techniques have been employed to overcome these issues but there is no consensus on the optimal normalization method for DBS metabolomics, and in some cases no normalization is used. We compared five normalization methods (hemoglobin (Hb), specific gravity (SG), protein, spot weight, potassium (K+)) to unnormalized data, and assessed sex-related differences in the DBS metabolome in 21 adults (group 1, n = 10 males, n = 11 females). The performance of each normalization method was evaluated using multiple criteria: (a) reduction of intragroup variation (pooled median absolute deviation, pooled estimate of variance, pooled coefficient of variation, NMDS and principal component analysis), (b) effect on differential metabolic analysis (dendrogram, heatmap, p-value distribution), and (c) influence on classification accuracy (partial least squares discriminant analysis, sparse partial least squares discriminant analysis error rates, receiver operating curve, random forest out of bag error rate). Our results revealed that Hb normalization outperformed all the other methods based on the three criteria and 13 different parameters; the performance of Hb was further demonstrated in an independent group of DBS from 18 neonates (group 2, n = 9 males, n = 9 females). Furthermore, we showed that SG and Hb are correlated in adults (rs = 0.86, p < 0.001), and validated this relationship in an independent group of 18 neonates and infants (group 3) (rs = 0.84, p < 0.001). Using the equation, SG = -0.4814Hb2 + 2.44Hb + 0.005, SG can be used as a surrogate for normalization by Hb. This is the first comparative study to concurrently evaluate multiple normalization methods for DBS metabolomics which will serve as a robust methodological platform for future environmental epidemiological studies.

An actionable annotation scoring framework for gas chromatography-high-resolution mass spectrometry.

Omics-based technologies have enabled comprehensive characterization of our exposure to environmental chemicals (chemical exposome) as well as assessment of the corresponding biological responses at the molecular level (eg, metabolome, lipidome, proteome, and genome). By systematically measuring personal exposures and linking these stimuli to biological perturbations, researchers can determine specific chemical exposures of concern, identify mechanisms and biomarkers of toxicity, and design interventions to reduce exposures. However, further advancement of metabolomics and exposomics approaches is limited by a lack of standardization and approaches for assigning confidence to chemical annotations. While a wealth of chemical data is generated by gas chromatography high-resolution mass spectrometry (GC-HRMS), incorporating GC-HRMS data into an annotation framework and communicating confidence in these assignments is challenging. It is essential to be able to compare chemical data for exposomics studies across platforms to build upon prior knowledge and advance the technology. Here, we discuss the major pieces of evidence provided by common GC-HRMS workflows, including retention time and retention index, electron ionization, positive chemical ionization, electron capture negative ionization, and atmospheric pressure chemical ionization spectral matching, molecular ion, accurate mass, isotopic patterns, database occurrence, and occurrence in blanks. We then provide a qualitative framework for incorporating these various lines of evidence for communicating confidence in GC-HRMS data by adapting the Schymanski scoring schema developed for reporting confidence levels by liquid chromatography HRMS (LC-HRMS). Validation of our framework is presented using standards spiked in plasma, and confident annotations in outdoor and indoor air samples, showing a false-positive rate of 12% for suspect screening for chemical identifications assigned as Level 2 (when structurally similar isomers are not considered false positives). This framework is easily adaptable to various workflows and provides a concise means to communicate confidence in annotations. Further validation, refinements, and adoption of this framework will ideally lead to harmonization across the field, helping to improve the quality and interpretability of compound annotations obtained in GC-HRMS.

Personal airborne chemical exposure and epigenetic ageing biomarkers in healthy Chinese elderly individuals: Evidence from mixture approaches.

BACKGROUND: Air pollution is associated with accelerated biological ages determined by DNA methylation (DNAm) patterns, imposing further risks of age-related adverse effects. However, little is known about the independent and joint effects of exposure to gaseous organic chemicals that may share a common source. METHODS: We conducted a panel study with the 3-day exposure assessment monthly among 73 Chinese healthy elderly people aged 60 to 69 years in Jinan, Shandong province during September 2018 to January 2019.Exposure to 26 ambient organic chemical contaminants were measured by wearable passive samplers, including volatile organic compounds, polycyclic aromatic hydrocarbons (PAHs), phthalates (PAEs), nitroaromatics (NIs), polybrominated diphenyl ethers, chlorinated hydrocarbons, and organophosphate esters. The Illumina MethylationEPIC BeadChip was used to measure DNA methylation levels in blood samples, and based on which, epigenetic ageing biomarkers, including Hannum clock, Horvath clock, DNAm PhenoAge, DNAm GrimAge, and DNAm estimator of telomere length (DNAmTL) were calculated. Linear mixed effect models were used to estimate the linear associations between 3-day personal chemical exposure and the epigenetic biomarkers, Weighted quantile sum (WQS) regression and the Bayesian kernel machine regression (BKMR) model were further used to evaluate the effect of chemical mixtures. RESULTS: Multiple linear mixed effects regression models showed that DNAmPhenoAge acceleration was significantly and positively associated with exposure to PAEs, NIs, and PAHs in healthy elderly individuals. Both WQS regression and BKMR models showed a significant positive association with DNAmPhenoAge acceleration with chemical exposures, in which the effect of di-n-butyl phthalate exposure showed the greatest importance. CONCLUSION: These findings suggest that exposure to a mixture of airborne chemicals significantly increase the acceleration of the epigenetic biomarker of phenotypic age. These findings serve to identify toxic chemicals in the air and facilitate the evaluation of their potentially severe health effects.

Personal air pollutant exposure monitoring in South African children in the VHEMBE birth cohort.

The burden of disease associated with environmental exposures disproportionately impacts residents of low- and middle-income countries. Children living in rural regions of these countries may experience higher exposure to insecticides from indoor residual spraying used for malaria control and household air pollution. This study evaluated environmental exposures of children living in a rural region of South Africa. Quantifying exposure levels and identifying characteristics that are associated with exposure in this geographic region has been challenging due to limitations with available monitoring techniques. Wearable passive samplers have recently been shown to be a convenient and reliable tool for assessing personal exposures. In this study, a passive sampler wristband, known as Fresh Air wristband, was worn by 49 children (five-years of age) residing in the Limpopo province of South Africa. The study leveraged ongoing research within the Venda Health Examination of Mothers, Babies, and their Environment (VHEMBE) birth cohort. A wide range of chemicals (35 in total) were detected using the wristbands, including polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides, phthalates, and organophosphate esters (OPEs) flame retardants. Higher concentrations of PAHs were observed among children from households that fell below the food poverty threshold, did not have access to electric cookstoves/burners, or reported longer times of cooking or burning materials during the sampling period. Concentrations of p,p'-DDD and p,p'-DDT were also found to be elevated for children from households falling below the food poverty threshold as well as for children whose households were sprayed for malaria control within the previous 1.5 years. This study demonstrates the feasibility of using passive sampler wristbands as a non-invasive method for personal exposure assessment of children in rural regions of South Africa to complex mixtures environmental contaminants derived from a combination of sources. Future studies are needed to further identify and understand the effects of airborne environmental contaminants on childhood development and strategies to mitigate exposures.

Assessing the External Exposome Using Wearable Passive Samplers and High-Resolution Mass Spectrometry among South African Children Participating in the VHEMBE Study.

Children in low- and middle-income countries are often exposed to higher levels of chemicals and are more vulnerable to the health effects of air pollution. Little is known about the diversity, toxicity, and dynamics of airborne chemical exposures at the molecular level. We developed a workflow employing state-of-the-art wearable passive sampling technology coupled with high-resolution mass spectrometry to comprehensively measure 147 children's personal exposures to airborne chemicals in Limpopo, South Africa, as part of the Venda Health Examination of Mothers, Babies, and Their Environment (VHEMBE). 637 environmental exposures were detected, many of which have never been measured in this population; of these 50 airborne chemical exposures of concern were detected, including pesticides, plasticizers, organophosphates, dyes, combustion products, and perfumes. Biocides detected in wristbands included p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT), p,p'-dichlorodiphenyldichloroethane (p,p'-DDD), p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), propoxur, piperonyl butoxide, and triclosan. Exposures differed across the assessment period with 27% of detected chemicals observed to be either higher or lower in the wet or dry seasons.

Development and Application of a Polydimethylsiloxane-Based Passive Air Sampler to Assess Personal Exposure to SARS-CoV-2.

Exhaled respiratory droplets and aerosols can carry infectious viruses and are an important mode of transmission for COVID-19. Recent studies have been successful in detecting airborne SARS-CoV-2 RNA in indoor settings using active sampling methods. The cost, size, and maintenance of these samplers, however, limit their long-term monitoring ability in high-risk transmission areas. As an alternative, passive samplers can be small, lightweight, and inexpensive and do not require electrical power or maintenance for continual operation. Integration of passive samplers into wearable designs can be used to better understand personal exposure to the respiratory virus. This study evaluated the use of a polydimethylsiloxane (PDMS)-based passive sampler to assess personal exposure to aerosol and droplet SARS-CoV-2. The rate of uptake of virus-laden aerosol on PDMS was determined in lab-based rotating drum experiments to estimate time-weighted averaged airborne viral concentrations from passive sampler viral loading. The passive sampler was then embedded in a wearable clip design and distributed to community members across Connecticut to surveil personal SARS-CoV-2 exposure. The virus was detected on clips worn by five of the 62 participants (8%) with personal exposure ranging from 4 to 112 copies of SARS-CoV-2 RNA/m3, predominantly in indoor restaurant settings. Our findings demonstrate that PDMS-based passive samplers may serve as a useful exposure assessment tool for airborne viral exposure in real-world high-risk settings and provide avenues for early detection of potential cases and guidance on site-specific infection control protocols that preempt community transmission.

A Novel Technique for Redox Lipidomics Using Mass Spectrometry: Application on Vegetable Oils Used to Fry Potatoes.

Vegetables oils, rich in polyunsaturated fatty acids, are vulnerable to oxidation during manufacturing, processing, and food preparation. Currently, individual oxidation products are not well characterized, and hence, the health impacts of these unique lipid species remain unknown. Here, we introduce an extensive oxidized lipidomics in silico tandem mass spectrometry library and integrate these libraries within a user-friendly software covering a comprehensive redox lipidomics workflow. We apply this workflow to olive, soy, and walnut cooking oil; comparing unheated oil, oil after deep frying potatoes, and oil after oven frying potatoes. We annotated over a thousand oxidized triglycerides across 273 features (many coeluted). This software was validated against traditional chemical assays of oxidation, known oxidized lipids in castor oil, synthesized standards, and an alternate software LPPtiger. Development of these new software programs for redox lipidomics opens the door to characterize health implications of individual oxidation products.

Exploring personal chemical exposures in China with wearable air pollutant monitors: A repeated-measure study in healthy older adults in Jinan, China.

The health impact of airborne contaminants has been challenging to assess due to current limitations in measurement technologies. The emergence of wearable passive samplers coupled with high resolution mass spectrometry (HR-MS) chemical analysis has enabled comprehensive characterization of personal exposures. We conducted a repeated-measure study among 84 older adults in Jinan, China, as part of the Biomarkers for Air Pollutants Exposure (China BAPE) study. Study objectives were: 1) to characterize the occurrence, magnitude, and distribution of personal exposure to airborne contaminants; 2) to evaluate the temporal variation of chemical exposures across the study population; and 3) to identify behavioral and environmental factors that influence the observed variance in chemical exposures. The FreshAir wristband was worn by participants for three consecutive days each month from September 2018 to January 2019 and collected with paired time-activity logs. Passive air samplers were also deployed in parallel at a local outdoor air monitoring station. Spearman's Rho trend test and trajectory cluster analysis were used to identify exposure trends and variation patterns, respectively. Out of the 70 airborne compounds of potential concern screened, 26 compounds from 10 chemical classes were found to be above detection thresholds across >70% of the study population. Personal exposures were predominantly characterized by nine polycyclic aromatic hydrocarbons (PAHs), four phthalates, three nitroaromatics, and two volatile organic compounds (VOCs). Phthalate personal exposures were positively correlated with outdoor temperatures while the inverse relationship was observed for certain PAHs (p < 0.05). Specifically, dimethyl phthalate (rs = 0.31) decreased as temperatures declined, while nitrobenzene (rs = -0.35) and naphthalene (rs = -0.40) increased as temperatures decreased. Compared to levels measured at the outdoor air monitoring site, personal exposure of phthalates was elevated (p < 0.05) and hexachlorobutadiene was lower across participants (p < 0.01). Personal exposure of these chemicals was further found to be weakly associated with daily duration participants spent outdoors. Individuals formed distinct clusters based on trajectories of chemical exposures across the sampling period (September to January), potentially suggestive of distinct emission sources. In conclusion, we demonstrate the feasibility of characterizing the occurrence and magnitude of personal exposure to airborne chemical contaminants using passive wristband samplers. The temporal variability of these personal exposure profiles was highlighted and with distinct trends identified across different groups of individuals. Future studies will integrate this data with other omics datasets collected from this population of Chinese older adults to investigate associations between exposure profiles and health relevant biomarkers, to provide evidence in feasibility of disease prevention through environmental improvements.

Reopening Schools After a Novel Coronavirus Surge.

The coronavirus disease 2019 (COVID-19) pandemic shook the world in ways not seen since the pandemic influenza of 1918-1919. As of late August 2020, over 25 million persons had been infected, and we will see the global death toll exceed one million by the end of 2020. Both are minimum estimates. All segments of society have been drastically affected. Schools worldwide have been forced to close due to illness and absenteeism, transmission and risk to vulnerable members of the school community, and community concerns. The decision to reopen school during a pandemic will have a tremendous impact on children's safety, growth, and well-being. Not opening invites social isolation and suboptimal educational experiences, especially for youth whose computing assets and online access are limited and those with special needs. The opening has hazards as well, and the mitigation of these risks is the topic of this chapter. Opening schools requires careful considerations of benefits, risks, and precautions. Guiding principles for safety and strategic application of the principles in each educational niche are critical issues to consider during school reopening. The fundamental principles of disease control involve school-directed initiatives (physical distancing and mask use, hand/face and surface cleansing, administrative controls, engineering controls) and individual-level risk reduction approaches to maximize adherence to new guidelines. The school-initiated "top-down" approaches and the individual-level "bottom-up" approaches must be synergized, as no single method will ensure safety. We discuss how to effectively layer strategies in each educational space to increase safety. Since the vulnerability of children has been heightened during this pandemic crisis, we highlight the special considerations for mental health support that should be considered by schools. The safety principles, disease control strategies, and other critical issues discussed here will serve as a starting point for developing a safe, comprehensive, and feasible reopening plan.