Background: The chemical exposome includes exposure to numerous environmental and endogenous molecules, many of which have been linked to reproductive outcomes due to their endocrine-disrupting properties. As several breast cancer risk factors, including age and parity, are related to reproduction, it is imperative to investigate the interplay between such factors and the chemical exposome prior to conducting large scale exposome-based breast cancer studies.

Objective: This pilot study aimed to provide an overview of the chemical exposome in plasma samples from healthy women and identify associations between environmental exposures and three risk factors for breast cancer: age, parity, and age at menarche.

Material and methods: Plasma samples (n = 161), were selected based on reproductive history from 100 women participating in the Northern Sweden Health and Disease Study, between 1987 and 2006. Samples were analyzed by liquid chromatography high-resolution mass spectrometry (LC-HRMS) for 77 priority target analytes including contaminants and hormones, with simultaneous untargeted profiling of the chemical exposome and metabolome. Linear mixed effects models were applied to test associations between risk factors and chemical levels.

Results: Fifty-five target analytes were detected in at least one individual and over 94,000 untargeted features were detected across all samples. Among untargeted features, 430 could be annotated and were broadly classified as environmental (246), endogenous (167) or ambiguous (17). Applying mixed effect models to features detected in at least 70% of the samples (16,778), we found seven targeted analytes (including caffeine and various per- and poly-fluoroalkyl substances) and 38 untargeted features, positively associated with age. The directionality of these associations reversed for parity, decreasing with increasing births. Seven separate targeted analytes were associated with age at menarche.

Significance: This study demonstrates how a comprehensive chemical exposome approach can be used to inform future research prioritization regarding associations between known and unknown substances, reproduction, and breast cancer risk.

The complex and dynamic nature of airborne fine particulate matter (PM2.5) has hindered understanding of its chemical composition, sources, and toxic effects. In the first steps of a larger study, here, we aimed to elucidate relationships between source regions, ambient conditions, and the chemical composition in water extracts of PM2.5 samples (n = 85) collected over 16 months at an observatory in the Yellow Sea. In each extract, we quantified elements and major ions and profiled the complex mixtures of organic compounds by nontarget mass spectrometry. More than 50,000 nontarget features were detected, and by consensus of in silico tools, we assigned a molecular formula to 13,907 features. Oxygenated compounds were most prominent, followed by mixed nitrogenated/oxygenated compounds, organic sulfates, and sulfonates. Spectral matching enabled identification or structural annotation of 43 substances, and a workflow involving SIRIUS and MS-DIAL software enabled annotation of 74 unknown per- and polyfluoroalkyl substances with primary source regions in China and the Korean Peninsula. Multivariate modeling revealed seasonal variations in chemistry, attributable to the combination of warmer temperatures and maritime source regions in summer and to cooler temperatures and source regions of China in winter.

Cetaceans face numerous anthropogenic chemical stressors in global oceans, yet there is a lack of studies that simultaneously assess their cumulative exposure to both legacy and emerging contaminants and their combined effects. To evaluate the susceptibility of fin whale (Balaenoptera physalus) to chemical pollution, this study employed for the first time a multidiagnostic molecular approach that integrates chemical exposomics and gene expression analysis in live-sampled skin and blubber biopsies from two distinct populations: the endangered Mediterranean subpopulation (Italy) and the vulnerable population from the Sea of Cortez (Mexico). Both marine regions are biodiversity hotspots characterized by different anthropogenic impacts, making them ideal for the assessment of heterogeneous contaminants exposure and their effects. Results revealed distinct exposure profiles in the two populations, with Mediterranean fin whales exhibiting higher concentrations of legacy pollutants such as polychlorinated biphenyls (PCBs), as well as plasticizers, perfluoroalkyl substances (PFAS), while both populations showed traces of pharmaceuticals and lifestyle-related chemicals (e.g., paracetamol, diclofenac, nicotine, UV filters) and other substances not previously reported in whales. Supported by 32 network correlations with gene expression relevant to transcriptional regulation, endocrine disruption, lipid homeostasis, and inflammation, our findings suggest that complex anthropogenic chemical exposures may compromise the health and reproductive viability of the endangered Mediterranean fin whales, affirming their importance as a global sentinel species, which reflects marine ecosystem integrity within the “One Health” framework.

Hydraulic fracturing flowback and produced water (HF-FPW) has raised significant concerns owing to its potential impact on aquatic organisms and human health. Understanding the chemical composition of HF-FPW is crucial for developing appropriate management and remediation strategies. Herein, we performed nontarget screening on hydrophobic organic chemicals in the particulate phase of FPW (P-FPW) using gas chromatography-Orbitrap mass spectrometry coupled with cheminformatic analysis. In total, 5807 features were discovered, with 209 annotated with positive confidence levels, which were further classified based on their chemical taxonomy and functional use information. We found that benzenoids dominated the chemical class, followed by hydrocarbons. The annotated chemicals were classified into fragrances, catalysts, antimicrobials, antioxidants, and other classes. Chemical overlap across countries (China vs. Canada) and wells was observed, with most chemicals reaching peak intensity within 24 or 48 h after the initial flowback and gradually decreasing. Approximately two-thirds of the identified or annotated chemicals have not been previously reported or included in existing HF-related databases, indicating expanded chemical coverage by the current screening workflow. A Toxicological Priority Index (ToxPi) scheme, which integrates chemical properties, ecological toxicities, and in vivo exposure potentials, was adopted to prioritize chemicals for further evaluation. Seven chemicals were proposed as prioritized compounds, of which the ester derivative of perfluorobutanoic acid, octacosyl heptafluorobutyrate (confidence level 2), exhibited the highest ToxPi score. Notably, most prioritized substances have limited toxicological data and are beyond the routine monitoring of the HF industry, highlighting significant gaps in our understanding of HF-related chemical content and environmental risk associated with water management.

Background: Maternal exposure to per- and polyfluoroalkyl substances (PFAS) has been linked to child neurodevelopmental difficulties. Neuroimaging research has linked these neurodevelopmental difficulties to white matter microstructure alterations, but the effects of PFAS on children's white matter microstructure remains unclear. We investigated associations between maternal blood concentrations of six common perfluoroalkyl sulfonates and white matter alterations in young children using longitudinal neuroimaging data. Methods: This study included 84 maternal-child pairs from a Canadian pregnancy cohort. Maternal second trimester blood concentrations of perfluorohexanesulfonate (PFHxS) and five perfluorooctane sulfonate (PFOS) isomers were quantified. Children underwent magnetic resonance imaging scans between ages two and six (279 scans total). Adjusted linear mixed models investigated associations between each exposure and white matter fractional anisotropy (FA) and mean diffusivity (MD). Results: Higher maternal concentrations of perfluoroalkyl sulfonates were associated with higher MD and lower FA in the body and splenium of the corpus callosum of young children. Multiple sex-specific associations were found. In males, PFHxS was negatively associated with FA in the superior longitudinal fasciculus, while PFOS isomers were positively associated with MD in the inferior longitudinal fasciculus (ILF). In females, PFOS isomers were positively associated with FA in the pyramidal fibers and MD in the fornix, but negatively associated with MD in the ILF. Conclusion: Maternal exposure to perfluoroalkyl sulfonates may alter sex-specific white matter development in young children, potentially contributing to neurodevelopmental difficulties. Larger studies are needed to replicate these findings and examine the neurotoxicity of these chemicals.

Environmental exposures to trace elements and perfluoroalkyl acids (PFAAs) could alter hypothalamic-pituitary-adrenal (HPA) function during pregnancy. Concentrations of trace elements measured in maternal red blood cells and PFAAs measured in maternal plasma, as well as maternal salivary cortisol were quantified from second trimester samples in 243 women from the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort. Regression analyses examine associations between trace elements and PFAAs, and cortisol awakening response (CAR), daytime cortisol and diurnal cortisol slope. Bayesian kernel machine regression (BKMR) analyses investigated mixture effects. In single exposure models, molybdenum (β = −0.99, 95 % CI = −1.74, −0.24) was negatively associated with CAR and lead was negatively associated with daytime cortisol (β = −13.3, 95 % CI = −25.65, −1.10); perfluoroheptanoic acid (PFHpA) was positively associated (β = 4.29, 95 % CI = 0.68, 7.90) with daytime cortisol. In sex-specific analyses molybdenum was negatively associated with CAR and lead was negatively associated with daytime cortisol in women who gave birth to female infants. PFHpA and perfluorohexanesulfonic acid (PFHxS), were positively associated with daytime cortisol in women who gave birth to male infants. Arsenic, mercury, zinc, PFHxS and perfluorooctanesulfonic acid (PFOS) were positively associated with diurnal cortisol slope in the women who gave birth to female infants. No associations survived correction for false discovery rate. In mixture models, molybdenum was the main contributor to CAR in women who gave birth to female infants; PFHpA contributed the most to daytime cortisol in women who gave birth to male infants. Exposure to trace elements and PFAAs in pregnancy may be associated with alterations in maternal HPA axis function.

Research investigating the prenatal chemical exposome and child neurodevelopment has typically focused on a limited number of chemical exposures and controlled for sociodemographic factors and maternal mental health. Emerging machine learning approaches may facilitate more comprehensive examinations of the contributions of chemical exposures, sociodemographic factors, and maternal mental health to child neurodevelopment. A machine learning pipeline that utilized feature selection and ranking was applied to investigate which common prenatal chemical exposures and sociodemographic factors best predict neurodevelopmental outcomes in young children. Data from 406 maternal-child pairs enrolled in the APrON study were used. Maternal concentrations of 32 environmental chemical exposures (i.e., phthalates, bisphenols, per- and polyfluoroalkyl substances (PFAS), metals, trace elements) measured during pregnancy and 11 sociodemographic factors, as well as measures of maternal mental health and urinary creatinine were entered into the machine learning pipeline. The pipeline, which consisted of a RReliefF variable selection algorithm and support vector machine regression model, was used to identify and rank the best subset of variables predictive of cognitive, language, and motor development outcomes on the Bayley Scales of Infant Development-Third Edition (Bayley-III) at 2 years of age. Bayley-III cognitive scores were best predicted using 29 variables, resulting in a correlation coefficient of r = 0.27 (R²=0.07). For language outcomes, 45 variables led to the best result (r = 0.30; R²=0.09), whereas for motor outcomes 33 variables led to the best result (r = 0.28, R²=0.09). Environmental chemicals, sociodemographic factors, and maternal mental health were found to be highly ranked predictors of cognitive, language, and motor development in young children. Our findings demonstrate the potential of machine learning approaches to identify and determine the relative importance of different predictors of child neurodevelopmental outcomes. Future developmental neurotoxicology research should consider the prenatal chemical exposome as well as sample characteristics such as sociodemographic factors and maternal mental health as important predictors of child neurodevelopment.

Marine ecosystems, from coastal waters to high seas, cover 71% of the Earth’s surface and influence all major biogeochemical cycles, climate regulation, and biodiversity conservation. Understanding how marine ecosystems respond to anthropogenic perturbations is therefore of paramount importance and is essential for developing strategies that will maintain critical ecosystem functions across diverse spatial and temporal scales.

Marine ecosystems, from coastal waters to high seas, cover 71% of the Earth’s surface and influence all major biogeochemical cycles, climate regulation, and biodiversity conservation. Understanding how marine ecosystems respond to anthropogenic perturbations is therefore of paramount importance and is essential for developing strategies that will maintain critical ecosystem functions across diverse spatial and temporal scales.

Most of the world’s population is concentrated in coastal regions. Anthropogenic perturbations to marine ecosystems have dramatically increased during the past century on pace with other global environmental and societal changes. A myriad of synthetic chemicals and perturbations to nutrient cycles are affecting ecosystem health, adding to stress imposed by warming, acidification, hypoxia, and other changes in the composition of seawater. Understanding and improving ocean health are intimately linked to human health through marine foods and are essential for conserving wildlife habitat, minimizing perturbations to biogeochemical cycling on our planet, and provisioning numerous ecosystem services. Seafood is one of the last wild foods that is consumed globally by billions of people, and marine farming activities are expected to increase substantially during the coming decade. Nevertheless, there are other connections between ocean and human health, including the water quality on coastlines, as well as in estuaries and bays as part of the land-to-sea aquatic continuum. In addition, coastal waters can perturb coastal air quality due to volatilization of pollutants and formation of sea-spray aerosol containing both pollutants and toxins from harmful algal blooms. In arid and semiarid locations globally, desalination of seawater for human consumption is needed; however, associated “brine” discharge and organism entrainment may have negative impacts on marine wildlife. These and other anthropogenic perturbations can affect the health of coastal and open sea biota and the health of humans. Thus, ocean health science is essential for diverse fields ranging from water quality to biodiversity protection to human health in this current era of global change.

During the past decade, there has been a large increase in the extent and scope of research conducted on marine ecosystems. These developments have benefited from the application of novel instrumentation, such as high-resolution mass spectrometry, novel sensors, and high-throughput sequencing of genomes and meta-genomes, among other omic sciences. Other advances include the development of new modeling and life cycle approaches that are now being transformed by improvements in data science and artificial intelligence techniques. Environmental Science & Technology and Environmental Science & Technology Letters, as central scientific journals on anthropogenic perturbations of ecosystems, have contributed to the scientific development of marine science in the context of ocean health, as evidenced by the virtual issue on “Ocean Health” that we have curated.

To further contribute to the development of this frontier of science, in this joint special issue of Environmental Science & Technology and Environmental Science & Technology Letters, we invite manuscripts that contribute to the integrated advancement of ocean health science around the world. Through this issue, we aim to provide a forum for high-quality research covering multiple dimensions of anthropogenic pressures on marine ecosystems, including but not limited to chemical and microbial pollution, acidification, desalination (and resulting “brine” discharge), deoxygenation, loss of species or habitats, disease outbreaks, harmful algal blooms, and eutrophication. Special attention will be given to studies embracing systems-based approaches to understand the interactions among these anthropogenic perturbations, effects of ongoing climate change, and potential implications for ecosystem services, biodiversity, and public health. Envisaged contributions will address these perturbations in coastal waters and/or high seas, or gradients of environmental complexity across highly impacted and pristine regions, covering all oceans and seas. Interdisciplinary and multidisciplinary approaches are especially welcome, as are studies that address issues related to environmental justice and research that involves citizen science.

For comprehensive chemical exposomics in blood, analytical workflows are evolving through advances in sample preparation and instrumental methods. We hypothesized that gas chromatography-high-resolution mass spectrometry (GC-HRMS) workflows could be enhanced by minimizing lipid coextractives, thereby enabling larger injection volumes and lower matrix interference for improved target sensitivity and nontarget molecular discovery. A simple protocol was developed for small plasma volumes (100-200 μL) by using isohexane (H) to extract supernatants of acetonitrile-plasma (A-P). The HA-P method was quantitative for a wide range of hydrophobic multiclass target analytes (i.e., log Kow > 3.0), and the extracts were free of major lipids, thereby enabling robust large-volume injections (LVIs; 25 μL) in long sequences (60-70 h, 70-80 injections) to a GC-Orbitrap HRMS. Without lipid removal, LVI was counterproductive because method sensitivity suffered from the abundant matrix signal, resulting in low ion injection times to the Orbitrap. The median method quantification limit was 0.09 ng/mL (range 0.005-4.83 ng/mL), and good accuracy was shown for a certified reference serum. Applying the method to plasma from a Swedish cohort (n = 32; 100 μL), 51 of 103 target analytes were detected. Simultaneous nontarget analysis resulted in 112 structural annotations (12.8% annotation rate), and Level 1 identification was achieved for 7 of 8 substances in follow-up confirmations. The HA-P method is potentially scalable for application in cohort studies and is also compatible with many liquid-chromatography-based exposomics workflows.