Ecotoxicology and Environmental Safety

Previously, we have demonstrated that certain ferric salts common in Archean waters, such as iron trichloride and ferric ammonium citrate, can protect liposomes from destruction by short-wavelength UVC light. In this study, we investigate the propagation of 254 nm UV radiation through aqueous FeCl3 solutions and its interactions with liposomes. We then consider these findings in the context of early Earth UV environment, discuss their implications for our hypothesis of the Darwinian evolution of liposomes, and integrate them with our previous experimental results.

Wildfire smoke has increasingly affected air quality across North America, raising concerns about the health effects of fine particulate matter (PM2.5) exposure, including potential impacts on brain health. However, relatively few studies have characterized personal PM2.5 exposure during these events using wearable monitoring. We examined daily personal PM2.5 concentrations during wildfire smoke episodes in southeast Michigan alongside neighborhood outdoor PM2.5 estimates. Four participants (one adolescent and three adults) wore AirBeam3 personal monitors during ongoing studies. Neighborhood outdoor PM2.5 was estimated using the average of three nearest PurpleAir outdoor air quality sensors, and wildfire smoke days were identified using state air quality advisories. Group-level descriptive statistics summarized personal and neighborhood outdoor PM2.5 and self-reported time spent outdoors. Exploratory within-participant analyses quantified associations between neighborhood outdoor and personal PM2.5 concentrations on smoke and non-smoke days. Neighborhood outdoor daily PM2.5 concentrations were higher during wildfire smoke days than non-smoke days (87.6 + 80.2 vs. 12.3 + 7.0 {micro}g/m3). Personal PM2.5 concentrations were more than five times higher during wildfire smoke days (28.2 + 20.0 vs. 5.1 + 4.7 {micro}g/m3) than non-smoke days. Within participants, every 10 {micro}g/m3 increase in neighborhood PM2.5 was associated with 2.3 {micro}g/m3 increase in personal PM2.5 concentrations. Wearable PM2.5 monitoring captured elevated personal exposures while providing individual-level exposure information beyond neighborhood outdoor air quality estimates. These findings demonstrate that wearable monitoring complements neighborhood air quality measurements by capturing individual-level exposure, providing a more comprehensive assessment of real-world wildfire smoke exposure for future studies examining the effects on brain health.

Hormesis is an important consideration in chemical risk assessment across most aquatic environments. Evidence suggests that hormetic responses are shaped by organismal physiological processes. Accordingly, predictions of hormesis under environmentally realistic conditions should account for physiological traits. Yet the role of these traits remains largely unexplored. This study investigated how baseline growth rate modulates antibiotic responses in the harmful cyanobacterium Microcystis and the underlying mechanisms. Results showed that at an antibiotic concentration of 200 ng L-1 (representing environmental concentration levels), slow-growing Microcystis populations exhibited an obvious growth enhancement more than 4-fold greater than that of fast-growing populations, and this enhancement was positively correlated with cellular reserves. A baseline growth rate below 0.19 day-1 emerged as the threshold below which hormetic responses were consistently observed. This study provides pioneering insights into how organisms' physiological states influence pollutant-induced hormetic responses in aquatic environments. Our findings point to a central principle for extrapolation that laboratory-derived toxicological responses may not translate directly to the field unless key physiological traits of the organisms are explicitly considered. In this regard, baseline growth rate and energy reserves may be key physiological traits for reliably predicting toxic effects at the population level. This study also makes an initial attempt to conceptualize a physiology-anchored framework for strengthening risk assessment of low-level emerging contaminants.

Background: Growing evidence links ambient air pollution, including fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3), to adverse effects on sleep. However, most prior research has relied on chronic exposure metrics and subjective sleep assessments, obscuring short-term dynamics and limiting physiological precision. To address these gaps, we examined associations of same-day and previous-day pollutant levels with both self-reported and device-measured sleep, using an ecologically valid design. Methods: Data were derived from the Budapest Sleep, Traits and Experiences Study, a 7-day observational study in which participants reported their daily activities and sleep quality ratings, and recorded EEG during sleep. Device-measured sleep outcomes included sleep efficiency, %REM sleep, sleep onset latency, and total sleep time. Daytime outdoor concentrations of PM2.5, NO2, and O3 were aggregated from monitoring stations. Linear mixed-effects models with a random intercept for participant were employed to evaluate associations between each pollutant and sleep outcome, being adjusted for age, sex, body mass index, education, weekday, season, temperature, physical activity, screen exposure, and traveling. Results: The analysis revealed that elevated O3 exposure on day 1 was associated with lower sleep efficiency and poorer perceived sleep quality on night 2. These findings survived correction for multiple comparisons, and held across multi-pollutant models and sensitivity analyses accounting for depression, insomnia, and chronotype. Notably, no robust day-to-night associations emerged for any pollutant. Conclusions: Overall, this study demonstrates a short-term relationship between outdoor ozone concentration and reduced sleep quality, even at levels deemed safe by current standards, which highlights the need for continued vigilance and regulations to protect health.

Air pollution is a growing public health concern. The developing fetus is particularly vulnerable, with exposure during pregnancy linked to negative developmental health outcomes. Teratogenic studies rely on the use of model organisms, such as the chick embryo, a well- established model of human development. However, existing protocols for the exposure of chick embryos to gaseous and aerosol pollutants have financial and technical limitations. Here, we present a novel, non-invasive method for the long-term exposure of chicken embryos to a gaseous toxin, carbon monoxide (CO). Exposure is performed inside airtight incubation boxes, which can be used in a standard laboratory incubator. We demonstrate reliable dosing of precise internal CO concentrations up to 200ppm, using a simple volumetric approach. Following optimization of key incubation parameters, temperature and turning frequency, we determined the impact of the system on embryo viability and development. Closed box incubation caused minor developmental delay but had no effect on chick embryo viability. Internal oxygen concentrations remained above hypoxic levels. No significant effects of exposure up to 200ppm CO were observed on embryo viability, weight or developmental stage. In conclusion, we present a non-invasive, affordable, accessible and technically straightforward exposure method for air pollutant teratogenicity studies. This method can be applied to other model systems and organisms beyond the chick embryo as well as to other gaseous and aerosol toxins. Thus, the system offers a suitable platform for future research on teratogenic doses, mechanisms and effects of air pollutants.

Tetrabromobisphenol A (TBBPA), is one the most widely produced brominated flame retardant, detected in human matrices including cord plasma, raising concern over its impact on embryonic development. Our previous work demonstrated that TBBPA disrupts craniofacial cartilage development in zebrafish; however, inhibition of bone morphogenetic protein (BMP) signaling did not rescue these defects, suggesting the involvement of alternative molecular mechanisms. Transcriptomic profiling revealed significant upregulation of aryl hydrocarbon receptor (Ahr) signaling genes, including cyp1a and cyp1c, as well as reactive oxygen species (ROS) responsive genes, such as nfe and gstp. Consistent with these findings, KEGG pathway enrichment analysis identified significant enrichment of pathways involved in xenobiotic metabolism, cytochrome P450-mediated metabolism, and molecular docking predicted stronger binding of TBBPA to Ahr2 than the Ahr2 agonist TCDD. Then we investigated the role of Ahr signaling and ROS in TBBPA-induced craniofacial cartilage defects using microinjection of Ahr2 translation-blocking morpholino and the antioxidant N-acetylcysteine (NAC), respectively. Immunohistochemistry confirmed concentration-dependent induction of Cyp1a and ROS at environmentally relevant concentrations (0.05;0.005 uM). Ahr2 knockdown using a translation-blocking morpholino rescued TBBPA-induced alterations in Cyp1a expression, ROS levels, DNA damage, the expression of chondrogenesis-related markers (Sox10 and Sox2), and epithelial to mesenchymal transition (EMT) markers (E-cadherin, N-cadherin, and Snail2). Furthermore, Ahr2 knockdown rescued several TBBPA-induced alterations in craniofacial cartilage parameters. Co-exposure of TBBPA with the antioxidant NAC rescued the ROS and DNA damage and rescued only ceratohyal cartilage length, whereas other cartilage parameters remained disrupted. These findings establish a causal role for the Ahr-Cyp1a axis in TBBPA-induced craniofacial cartilage developmental toxicity and identify ROS as an important downstream contributor, indicating that both ROS-dependent and ROS-independent Ahr mechanisms underlined the observed TBBPA induced craniofacial defects.

Breast cancer is the most common cancer in women worldwide and chemicals disrupting estrogen or progesterone signaling are recognized as potential risk factors. However, chemicals that alter the mammary gland (MG) development and function remain understudied, highlighting the need for additional research in this area. To address this gap, we investigate the relevance of using high-content imaging assays and more specifically, Cell Painting technology to measure cell morphology perturbation caused by chemical exposure and identify morphological features that could characterize mammary carcinogens (MC) risk factors. Using a dataset of MC and non-mammary carcinogens (Non-MC) with Cell Painting profiles from the JUMP-CP dataset, we retrieved 51 compounds: 28 MC, 23 non-genotoxic Non-MC. We characterized the morphological data by non-linear dimensionality reduction (UMAP) and hierarchical clustering. We, then, developed a Guilt-By-Association (GBA) framework comparing multiple configurations of similarity metrics, risk-score aggregation approaches and features representations. Morphological profiles clustered by mechanism of action rather than carcinogenicity label: genotoxic MC produced strong perturbations in endoplasmic reticulum, mitochondria, nucleus, and RNA compartments, whereas hormonally active compounds were indistinguishable from controls, reflecting the lack of functional steroid hormone receptors in the cell line used. Our best GBA configuration achieved an AUC-ROC of 0.630 and an AUC-PR of 0.696. Applied prospectively to endocrine disruptors chemicals, it prioritized clofentezine, 3-methylpyrazole, resorcinol, 2-tert-butyl-4-methoxyphenol, and thiabendazole as candidates for confirmatory testing. This study provides a transparent, interpretable tool for prioritizing chemicals in mammary carcinogenicity assessment, highlights limitations and clarifies where Cell Painting datasets must be complemented by hormone-sensitive models.

Urban green infrastructure is increasingly promoted as a public-health intervention, yet the biological features that determine exposure to potentially beneficial plant-derived volatile compounds remain poorly understood. Here we quantified airborne terpenes and terpenoids across five contrasting urban greenspaces in Oxford, UK, and related chemical profiles to plant diversity, vegetation structure and surrounding habitat characteristics. Ambient air samples collected across spring and summer were analysed by thermal-desorption gas chromatography-mass spectrometry, alongside field surveys of taxonomic richness, canopy cover, vegetation volume and ground composition. Terpene and terpenoid scentscapes differed strongly among sites and through time, with monoterpenes dominating detected profiles. Sites with greater plant richness and greater vegetation volume below 1.5 m consistently showed higher terpene/terpenoid abundance, whereas total vegetation volume, canopy cover and tree abundance were weaker and less consistent predictors. These relationships were specific to plant-associated chemical classes and were not observed for predominantly anthropogenic volatile compounds. These patterns were resolved across only five independent sampling sites, and the relationships reported here should therefore be considered exploratory. Our findings suggest that human exposure to plant-derived volatiles in cities may be maximised not simply by increasing tree cover, but by designing biodiverse, structurally complex lower-to-mid-storey vegetation within the breathing zone. These results provide an empirical basis for incorporating scentscape ecology into health-oriented urban greenspace design.

Benzyl paraben (BzP) and butyl paraben (BuP) are used as preservatives and antimicrobial agents in cosmetics, pharmaceuticals, and foods. BzP and BuP have been detected in urine, placental tissue, and ovarian follicular fluid and are understudied with regards to their endocrine activity, raising concerns on their impact to the reproductive system. We tested the hypothesis that BzP and BuP are toxic to the ovary and behave similarly to other structurally similar endocrine disrupting chemicals, such as phthalates and terephthalates, by altering hormone levels and impacting cell growth and gene expression in vitro. Untreated mouse antral follicles were exposed to vehicle, 0.1, 1, 10, or 100 g/mL BzP, BuP, or the BuP analog monobutyl terephthalate (MBuTP) for 96 hours. The highest dose of BzP and BuP were cytotoxic to follicles, suggesting that medium chain length hydroxybenzoates are more cytotoxic to the ovary than corresponding terephthalic acids. BzP significantly increased levels of estradiol and testosterone compared to control. BuP decreased follicle growth and disrupted expression of cell cycle regulators, similar to phthalates. The peroxisome proliferator-activated receptor gamma (PPARg)-transcriptionally controlled gene Fabp4 was significantly upregulated by both BzP and BuP, whereas MBuTP upregulated all four PPAR target genes and decreased follicle growth. Overall, BzP, BuP, and MBuTP disrupted hormone levels, follicle growth, and cell cycle progression, suggesting similarities in toxicity to phthalates and potential endocrine disruption. Further study should be done on the reproductive toxicity and endocrine disrupting effects of chemicals similar in structure to phthalates to reduce exposure to endocrine disruptors and inform design of safer replacements.

Polycyclic aromatic hydrocarbons (PAHs) are hazardous organic contaminants for which microbial bioaugmentation is a promising remediation strategy, but poor persistence of introduced microorganisms can limit efficacy. Encapsulation may improve persistence, yet the influence of capsule design, microbial species, and environmental conditions on performance remains poorly understood. We evaluated alginate encapsulation of the PAH-degrading bacteria Pseudomonas putida and Novosphingobium aromaticivorans across nutrient conditions and capsule formulations. Encapsulation effects varied by species and medium, influencing growth rate, maximum cell density, overall growth, and lag time; notably, encapsulation shortened lag time of N. aromaticivorans in sRB15 medium (36.9 h to 3.9-5.3 h). Enumeration methods also affected apparent cell recovery. After 8 weeks, encapsulation had no significant effect on P. putida but resulted in increased concentrations of N. aromaticivorans relative to planktonic cultures (1.22 x 10; vs. 2.05 x 10; CFU/mL). Capsule composition further influenced cell retention: increasing alginate approximately doubled capsule-associated cell concentrations, while chitosan coatings reduced cell concentrations within capsules without affecting external concentrations. These findings demonstrate that the benefits of encapsulation are species- and environment-dependent and that capsule formulation can be tuned to influence bacterial persistence and release, informing the design of encapsulated inoculants for bioaugmentation applications.

Background: Exercise training is a cornerstone intervention for cardiovascular disease, yet large cohort studies have reported attenuation of physical activity benefits at elevated air pollution concentrations, creating uncertainty around exercise prescription in polluted settings where cardiovascular disease burden is greatest. Objectives: To determine whether ambient PM2.5 concentration modifies the cardiovascular benefits of structured exercise training, using a global sample of trials spanning a >100-fold pollution gradient. Methods: We conducted a systematic review and multilevel meta-analysis of exercise training interventions reporting pre-post changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), peak oxygen uptake (VO2Max), or resting heart rate (HR) in adults. Annual ambient PM2.5 concentrations (3.5-283 g/m3) were assigned to each study location from CAMS ERA5 reanalysis data. Three-level random-effects models with cluster-robust variance estimation accounted for arms nested within studies. PM2.5 meta-regression was conducted unadjusted and adjusted for world region, exercise mode, trial duration, and health condition, with subgroup analyses by exercise mode and hypertension status. Results: Across 465 studies (27,629 participants), exercise training produced clinically meaningful benefits for all outcomes (SBP - mmHg, DBP - mmHg, VO2Max +3.2 ml/kg/min, HR - bpm; all p < 0.001), with benefits consistently larger in higher-pollution settings. Hypertensive participants showed the greatest improvements, particularly from aerobic exercise (SBP standardised mean difference 0.396 in the Low vs 1.020 in the High PM2.5 stratum). Although aerobic and resistance training participants experience similar chronic ambient PM2.5 exposure, only aerobic exercise showed a stratum gradient (interaction p = 0.074). Discussion: Exercise training delivers clinically meaningful cardiovascular benefits at every pollution level tested. The larger benefits observed in higher-pollution settings reflect the greater cardiovascular risk burden of those populations, and hypertensive patients stand to gain the most, particularly from aerobic exercise.

Objective: Environmental pollutants are increasingly recognized as potential risk factors for metabolic dysfunction-associated steatotic liver disease (MASLD), yet the effects of mixed exposures and underlying mechanisms remain unclear. We evaluated associations between environmental chemical mixtures and MASLD and the mediating role of inflammation-related biomarkers. Methods: We analyzed 60 environmental chemicals across six categories among 39,061 U.S. adults from the National Health and Nutrition Examination Survey (NHANES) 1999-2020. Principal Component Pursuit with Principal Component Analysis (PCP-PCA) identified latent exposure patterns. MASLD was identified using multisociety Delphi consensus criteria and the Hepatic Steatosis Index (HSI [&ge;] 36). Logistic regression, restricted cubic spline models, and mediation analysis were applied. Results: PCP-PCA generated 5-17 dimensions per chemical category, with first-dimension variance contributions ranging from 30.70% to 98.88%. Six dimensions from four categories were retained, with phthalate esters (PAEs) and organophosphate flame retardants (OPFRs) showing the most consistent associations with MASLD. PAEs Dim.1, explaining 90.71% of variance, showed a significant non-linear dose-response association (P-nonlinear = 0.0001). Significant associations were identified for mono-isobutyl phthalate (MiBP; OR 1.12, 95% CI 1.07-1.19), mono(carboxyoctyl) phthalate (MCOP; OR 1.08, 95% CI 1.02-1.14), mono(carboxynonyl) phthalate (MCNP; OR 1.12, 95% CI 1.03-1.21), and bis(1,3-dichloro-2-propyl) phosphate (BDCP; OR 1.15, 95% CI 1.08-1.23). C-reactive protein (CRP) and red cell distribution width (RDW) were the primary mediators, accounting for 32.42% and 19.62% of the MiBP-MASLD association, respectively (both p < 0.0001). Conclusion: Environmental co-exposure, particularly to PAEs and OPFRs, was associated with higher MASLD risk, with systemic inflammation potentially contributing to these associations.

Food security is one of the major ongoing global anthropic challenges, driving the intensification of agricultural systems notably through the widespread use of phyto-pharmaceutical products (PPPs). Although effective for maximizing production yields through pest control, PPP contamination is pervasive across the entire agroecosystem, raising concerns about human and non-target species exposure and health effects. Organic farming has therefore been promoted as a sustainable alternative to ensure human food security and mitigate these impacts. Yet, the pathways of PPP non-target organisms contamination are insufficiently understood. While most research has focused on ingestion as the primary route of exposure, increasing evidence suggests more complex contamination dynamics. In this study, we investigated the role of food intake in shaping PPP contamination profiles in semi-captive grey partridges (Perdix perdix). To do so, 80 birds were housed in open aviaries within an agricultural landscape and fed either conventional or organic grains over a five-month period. After drawing their PPP blood profiles at the end of the exposure period, we assessed their loads and compared the pesticide prevalence and abundance between food treatments. We found similar quantity and diversity of PPP residues in blood from conventionally- and organically-fed partridges, with few differences in specific PPP compounds. Overall, these findings suggest that food intake is not necessarily the only source of contamination for non-target organisms, with alternative pathways (e.g., inhalation, dermal contact, soil and water exposure) likely playing a substantial role. Integrating multi-pathway contamination monitoring across trophic levels within a One Health framework would now be essential to better understand and mitigate PPP contamination risks. Submitted to PCI: Ecotoxicology and Environmental Chemistry

Per- and polyfluoroalkyl substances (PFAS) and phthalate metabolites are understudied in follicular fluid of women undergoing assisted reproduction. We characterized these in previously collected follicular fluid from patients at a Nebraska fertility clinic (August 2022 to June 2025) and retrieved demographics and clinical characteristics from fertility records. Spearman correlations and nonparametric tests evaluated PFAS and phthalate correlations and exposure differences by age, race, BMI, and urbanicity. Seven PFAS and four phthalate metabolites were detected in at least half of participants. PFOS and PFHxS concentrations were higher in younger women, and mono-isobutyl phthalate (MiBP) was higher in younger and non-White women. PFAS and phthalate correlations were weak, and exposures did not differ by urbanicity, indicating multiple chemical exposures in follicular fluid with sociodemographic disparities.

Endocrine-disrupting chemicals can target ovaries and interfere with key milestones of reproduction. Previously, we found that mixtures of the chemical exposome measured in follicular fluid (FF) were cumulatively associated with lower oocyte yield. Because ovaries age faster than many other organs, our current aim was to evaluate associations of FF chemical mixtures with epigenetic age acceleration and epigenetic pathways in FF cells. FF was collected during oocyte retrieval from 76 patients undergoing assisted reproduction in Atlanta. The exposome was measured using untargeted high-resolution mass spectrometry with gas (GC) and liquid (LC) chromatography. Weighted quantile sum (WQS-RS) indices were constructed for three mixtures of chemicals in association with oocyte yield, separated by instrument configuration (GC, LC-HILIC, LC-C18). DNA methylation was measured from the cellular component of FF using Illumina MethylationEPIC BeadChip, with age acceleration based on the GrimAge clock. Regression and pathway enrichment analyses elucidated relationships between chemical exposures or mixture indices and epigenetic markers, adjusted for age and technical covariates. All three chemical mixture indices were associated with epigenetic age acceleration in FF (p<0.05). For example, a standard-deviation increase in the GC-detected mixture was associated with 0.23 standard-deviations higher accelerated aging (95% CI: 0.0058-0.45; p=0.048). Twenty-seven frequently detected chemicals, including benzo[a]pyrene, plasticizers, flame retardants, forever chemicals, and pesticides, were associated with epigenetic pathways related to ovarian follicle growth and hormone signaling (p<0.05; six under false discovery rate<5%). In summary, environmental chemicals may accumulate in ovaries, contribute to accelerated epigenetic aging of ovarian somatic cells, and potentially affect follicle development.

Background: Millions of textile and agricultural workers inhale organic dust containing endotoxin, an exposure associated with impaired respiratory function. However, the underlying biological pathways remain unclear. We conducted a two-cohort epigenome-wide association study (EWAS) to identify airborne endotoxin-associated DNA methylation (DNAm) alterations and pathways. Methods: In the discovery phase, we compared blood DNAm in 281 endotoxin-exposed cotton workers and 253 unexposed silk-workers from the Shanghai Textile Worker Study (STWS) measured using Illumina MethylationEPICv2 arrays. STWS endotoxin assessment combined detailed work histories and onsite measurements. For targeted parallel validation, we tested STWS signals in 686 incident lung cancer cases and 683 matched controls from the Shanghai Women's Health Study (SWHS), using occupation-derived low, medium, or high exposure-intensity ranks based on published evidence. To gain biological insight, we analyzed pathway enrichment, immune-cell composition, DNAm inflammation risk scores (IRSs), and respiratory phenotype associations in STWS. Results: In STWS, we identified 36 epigenome-wide significant DNAm sites (P<5e-8), of which, 35 were hypomethylated. Among 30 sites testable in SWHS, 18 had concordant effect directions, and four were nominally significant: cg11869499 (POLG; P=0.041), cg16290931 (TSKS; P=0.044), cg05019530 (EPIC1; P=0.042), and cg26033526 (PSMB9/TAP1; P=0.013). Enrichment implicated immune and signal-transduction pathways, including IgSF cell-adhesion-molecule signaling (FDR=8.2e-6;). Neutrophil were higher in cotton workers than in silk workers (63.5% vs 58.9%, p=7.52e-10). Cumulative endotoxin was associated with higher CRP-based IRSs, which showed the most consistent associations with lower lung function and airflow obstruction. Conclusions: Our EWAS findings suggest that occupational endotoxin may operate partly through immune-cell composition and inflammatory pathways.

Background Staying physically active is essential for healthy ageing. Exposure to high levels of air pollutants such as particulate matter (PM) is associated with less active, more sedentary lifestyles in older adults. Whether results extend to typical fluctuations in daily PM exposure is unclear. We examined associations of higher-than-usual personal exposure to PM (PM2.5 and PM10) with next-day movement behaviour in older adults, assessed using concurrently worn personal air quality monitors and accelerometers. Methods The present study used 304 days of data from 67 adults aged 50-85 years living in the UK. For five days, participants wore accelerometers 24-hours per day and personal air quality monitors during waking hours. Average daily time spent in movement behaviours (moderate-to-vigorous physical activity [MVPA], light physical activity [LPA], sedentary behaviour [SB]) and step count was extracted from accelerometers, and average daily exposure to PM2.5 from personal air quality monitors. PM10 was examined in secondary exploratory analyses. We used linear mixed models to examine within-person associations of deviation from usual PM exposure with next-day movement outcomes, with estimates presented for 'usual' (individual mean) and 'higher-than-usual' (+1 interquartile range, equivalent to 2.6 g/m3 beyond individual mean PM2.5 exposure and 2.8 g/m3 beyond individual mean PM10 exposure) exposure. Analyses were repeated using area-based PM estimates. Results Compared with usual exposure, higher-than-usual PM2.5 was associated with 8 minutes less LPA (95% CI=-14 to -2) and 483 fewer steps (-855 to -82) on the following day. Exposure to higher than usual PM10 was associated with 8 minutes less LPA (-13 to -3), 8 minutes more SB (0 to 15), and 412 fewer steps (-739 to -85) on the following day. There was no association with MVPA, and no associations when area-level PM estimates were used as opposed to estimates from personal air quality monitors. Conclusions Typical daily variability in PM exposure in a setting with relatively low overall PM levels was associated with modest next-day differences in movement behaviour in older adults. Higher-than-usual PM exposure was associated with less next-day activity and more sedentary time. Personal monitoring may be important for capturing short-term exposure-behaviour associations. Trial registration N/A

Despite their fundamental role in sustaining terrestrial biodiversity and ecosystem functioning, soils are increasingly contaminated by pesticides, often occurring as complex mixtures. Understanding chemical uptake, distribution, and elimination in soil organisms is essential for reliable risk assessment. We investigated the toxicokinetics of a binary mixture of imidacloprid and epoxiconazole in the earthworm Aporrectodea caliginosa. Single-substance experiments were conducted to estimate uptake and elimination rates, and allowed the implementation of single substance toxicokinetic models. A mixture experiment tested five concentration ratios to assess potential interactions. Epoxiconazole, an azole fungicide, exhibited rapid uptake and elimination (k_u = 1.9 gsoil*gworm-1*d-1; k_e = 1.7 d-1), resulting in low bioaccumulation (BAF = 0.9), whereas imidacloprid, a neonicotinoid insecticide, accumulated slowly with low elimination (k_u = 1.6 gsoil*gworm-1* d-1; k_e = 0.12 d-1), producing high bioaccumulation (BAF = 20). The explicit inclusion of the 24-hour Petri dish depuration phase proved to be critical, especially for epoxiconazole, highlighting the influence of gut-clearance procedures on apparent kinetics. In accordance with only a small synergistic effect in the mixture, no toxicokinetic interactions were detected in the mixture; internal concentrations of each compound were consistent across ratios. Concentration-dependent patterns were observed, with indications of a saturation process at high exposure levels for imidacloprid, and an increased BAF at high concentrations for epoxiconazole. This finding questions the use of single, concentration-independent bioaccumulation factors for hazard assessment and highlights the value of integrated TKTD approaches.

Lead (Pb) exposure is strongly associated with cardiovascular diseases, but the effects of developmental Pb exposure on the electrophysiological properties of human cardiomyocytes have not yet been investigated. Using human induced pluripotent stem cell (iPSC)-derived cardiomyocytes, we investigated the effects of human-relevant Pb exposure during ventricular cardiomyocyte differentiation on action potential properties and calcium dynamics in differentiated myocytes. We exposed 2 iPSC lines, from 1 male and 1 female donor, to Pb (0.5 or 5 micromolar) or control during only the first 8 days of differentiation, prior to functional maturation. Differentiation was carried out using an established protocol involving temporal modulation of Wnt signaling, followed by purification and maturation of contractile myocytes. We measured action potential properties and calcium dynamics using fluorescent dyes and optical mapping. We hypothesized that Pb exposure would adversely affect cardiomyocyte function, with effects persisting after cessation of exposure. In keeping with this hypothesis, we found significant Pb-induced changes in calcium (Ca) transients and action potential dynamics that were concentration and cell line specific and persisted well after exposure had ended. In the female cell line, beat frequency significantly increased with Pb exposure for both action potentials and Ca transients, while in the male cell line, beat frequency significantly decreased with Pb exposure for action potentials and increased for Ca transients. For voltage measurements, we observed significantly increased arrythmias with Pb exposure in both cell lines. Significant changes in repolarization and recovery time (for voltage and Ca, respectively) were present with Pb exposure in both cell lines. Gene expression of Ca transporters/channels and K channels were not affected, suggesting that persistent effects of Pb exposure on cardiomyocyte electrophysiology may occur through post-translational mechanisms. Overall, this study paves the way for future work to examine how exposure to Pb impacts long-term cardiac function through developmental programming.

Here, oyster larval developmental abnormalities within a New England hatchery were linked to a common UV sterilization technique that has been used for over 20 years. Because of the known link between phytoplankton oxylipins and egg mortality in copepods, we hypothesized that UV pretreatment of seawater results in the production of oxylipins that inhibit larval digestion of microalgae. We used lipidomics to observe changes in the organic compounds dissolved in estuarine seawater when filtered and when filtered and pretreated with UV. UV treatment resulted in an increase in the relative abundance of oxylipins associated with cyanobacteria, fungi, and macroalgae in 2020, whereas oxylipins typically produced by diatoms were more abundant in the UV treatments from 2021. Oxylipin concentrations were higher in 2020, when the hatchery reported the most severe problems with larval development. Removing the UV step allowed continued larval production in both years. However, the lack of UV sterilization led to an unidentified bacterial pathogen in 2021, which nearly decimated the overall seasonal production of oyster seed. To follow up in a more controlled environment, the larvae were exposed to exogenous oxidized lipids, which resulted in the same digestive syndrome and histological symptoms as the endogenous suite of compounds produced by UV. Further investigation of the lipidomes revealed that oxylipins were only one class of potentially harmful compounds linked to UV sterilization, and the dissolved concentrations of secondary metabolites associated with higher plants, a wide range of pharmaceuticals, and anthropogenic organic pollutants also increased under UV light. Future efforts will explore the sources of these compounds, the mechanisms by which they inhibit oysters, and whether this is an emerging environmental problem for other ecosystems and shellfish hatcheries. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=137 SRC="FIGDIR/small/738347v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@43d06corg.highwire.dtl.DTLVardef@2894daorg.highwire.dtl.DTLVardef@449e59org.highwire.dtl.DTLVardef@f81983_HPS_FORMAT_FIGEXP M_FIG C_FIG