Bisphenols are widely used in industrial applications to produce plastics and other consumer products. Among them, bisphenol A (BPA) is the most extensively studied due to its well-documented endocrine-disrupting effects and its association with various health conditions, including metabolic disorders and liver disease. Due to its known toxicity, BPA use has been restricted in many countries, leading to the emergence of several structural analogs. Recent studies have shown that BPA can interfere with normal liver metabolism by interacting with Liver X Receptor-beta (LXRβ). Although some BPA analogs have also been reported to cause toxicity, their exact effects on LXRβ remain unclear. In this study, we investigated the interaction between BPA analogs and LXRβ using molecular docking. BPA and the known LXRβ ligand G58 were used as reference compounds. The top 10 BPA analogs were further evaluated for their pharmacokinetics and pharmacodynamics properties. Molecular dynamics simulations over 100 ns were performed to study the dynamic behavior of LXRβ in complex with these analogs. Binding free energies were then calculated using the MM-PBSA method. Our results showed that several BPA analogs exhibited predicted stronger binding activities to LXRβ than BPA. Although some analogs shared similar pharmacokinetic and pharmacodynamic profiles with BPA, their stronger interaction with LXRβ raises concerns about their potential hepatotoxicity. This study employs a robust in silico framework to predict that commonly used BPA alternatives may pose a greater potential hepatotoxic risk than the banned parent compound, highlighting the value of computational approaches in prioritizing chemicals for further experimental assessment.

DILI is the leading cause of drug failure in clinical trials and withdrawal from the market. Certain intrinsic mechanisms of injury have been characterized such as the direct cytotoxicity exerted by NAPQI, a reactive metabolite of acetaminophen. However, presentation of DILI is highly heterogeneous with several idiosyncratic presentations being observed in patients. Such manifestations are often linked to aberrant immune activation although the biochemical mechanisms directing such responses currently evade complete understanding. This review consolidates current literature findings into potential mechanisms of immune-mediated DILI as well as risk factors which may polarize both the liver itself and certain individuals toward a drug-reactive phenotype. Current theories implicate neoantigen formation as a result of the generation of drug-protein adducts by both parent drugs and reactive metabolites. Responses to such adducts can be restricted to the presence of certain HLA alleles though these associations are identified through epidemiological means rather than mechanistic investigations. Further, susceptibility to DILI can be linked to nuance in the T-cell responses to HLA displayed antigens where basal levels of effector molecules and inflammation as well as the presence of liver resident immune cells, such as natural killer T-cells, can augment drug-specific immune responses.

Recent studies indicate that microplastics and nanoplastics (MNPs) act as key vectors for contaminants including cadmium (Cd). However, the bioavailability induced by their interaction remains controversial. Since both MNPs and Cd primarily accumulate in the liver after ingestion by organisms, hepatotoxicity induced by coexposure to MNPs (100 mg/kg body weight (BW)), 100 nm and 1 μm polystyrene (PS), and Cd (5 mg/kg BW) was examined in this study. Single or combined exposure models were established, and gavage was performed 5 times a week for 5 weeks. We observed that polystyrene (PS) accumulated in the mice liver. In comparison to the control group, all exposure groups exhibited significantly increased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, altered hepatic antioxidant enzyme activities, decreased P62 protein expression, and elevated Beclin-1 expression and LC3II/I ratios, indicating that PS alone or in combination with Cd disrupted liver structures and induced excessive autophagy and oxidative damage. Specifically, the 1 μm PS group induced significantly stronger hepatotoxic effects than the 100 nm PS group. In contrast, for 100 nm PS, although it was less toxic when administered alone, it significantly enhanced the Cd-induced liver injury. Notably, triple exposure to 100 nm PS, 1 μm PS, and Cd resulted in the most severe liver dysfunction, histopathological alterations, and activated cellular autophagy. Mechanistic investigations revealed that PS exposure alone or in combination with Cd triggered excessive autophagy and oxidative stress in hepatocytes by interfering with the PI3K/AKT/mTOR signaling pathway, thereby mediating liver injury. This study innovatively demonstrates that coexposure to different-sized PS particles and Cd can lead to complex liver injury patterns while particle size influences their combined hepatotoxicity with Cd.

The rapid rise of e-cigarette (vape) use over the past decade has raised significant public health and environmental concerns. While marketed as safer alternatives to combustible cigarettes, e-cigarettes generate complex aerosols that expose both users and nonusers to potentially harmful compounds. Vaping produces aerosols containing active ingredients (such as nicotine or cannabinoids), flavoring agents, metals, carbonyls, reactive oxygen species, and ultrafine particles that can deposit throughout the respiratory tract. Beyond direct inhalation, nonusers are also subject to secondhand and thirdhand exposure through inhalation of exhaled aerosols and contact with surface-deposited residues. These aerosols undergo dynamic physicochemical transformations, including gas-particle partitioning, oxidation, and aging processes, that may enhance their toxicity by increasing the abundance of reactive and oxygenated species. Emerging evidence suggests that passive exposure may pose disproportionate risks to vulnerable populations, such as children, adolescents, pregnant women, and the elderly. In addition, the rapid expansion of disposable e-cigarette products introduces new environmental hazards. Improper disposal of devices containing plastics, metals, lithium batteries, and residual e-liquids contributes to electronic waste, microplastic pollution, and leaching of toxicants, such as nicotine, heavy metals, and persistent organic pollutants. Despite growing research, critical gaps remain in understanding the long-term health effects of passive vaping, the environmental transformation of e-cigarette emissions, and the ecological consequences of disposable device waste. This review highlights current evidence on the composition, transformation, and toxicity of e-cigarette aerosols, examines the environmental burden of e-cigarette waste, and outlines future research priorities needed to inform regulatory policies and protect public health.

Incense burning is a major indoor source of fine and ultrafine particulate matter (PM), yet the size-chemistry determinants of its cellular toxicity remain underdefined. We characterized aerosols from three commonly used incense types using Aerodynamics Particle Sizer (APS)/Scanning Mobility Particle Sizer (SMPS) for sizing, Micro-Orifice Uniform Deposit Impactor (MOUDI) for size segregation, and water-soluble phase (WP) or organic-phase (OP) extraction to generate incense aerosol extracts (IAEs). Across A549, HEK293T, and SH-SY5Y cells, OP-IAEs from fraction III (0.18-0.10 μm) and IV (<0.10 μm) exhibited the strongest cytotoxicity, oxidative responses, and mitochondrial dysfunction. Type A incense (sandalwood-dominant) IAEs consistently showed the highest potency among the investigated incenses. Mechanistic assays revealed that ultrafine OP-IAEs, elevated intracellular H2O2, decreased mitochondrial membrane potential (MMP), depleted ATP, and activated apoptosis (caspase-3), pyroptosis (caspase-1), and autophagy-associated pathways. Moreover, ≥80% of all emitted particles were <0.18 μm and were disproportionately enriched in OP constituents across incense types. Collectively, these results identify ultrafine, lipophilic aerosol fractions as key drivers of oxidative-mitochondrial injury and programmed cell death, establishing a size- and phase-resolved framework for assessing incense-related health risks and for guiding exposure mitigation in incense-rich indoor environments.

The increasing use of flavored electronic cigarettes (e-cigarettes) raises concerns about their potential impact on the emission of harmful chemicals, particularly carbonyl compounds. This study systematically examines the effects of eight representative flavoring chemicals from four major classes including esters (ethyl acetate, ethyl butyrate), alcohols (menthol, ethyl maltol), aromatic aldehydes (benzaldehyde, vanillin), and terpenes (limonene, linalool) under varying power outputs (50 and 90 W), base liquid composition [propylene glycol (PG)/vegetable glycerin (VG) ratios (80:20, 50:50, and 20:80)], and flavor concentrations (1 and 5 mg/mL). Across all conditions, flavored e-liquids tend to produce carbonyl emissions that are higher than those of unflavored controls. Terpene-based flavors showed the strongest effects, with formaldehyde emissions being up to 2-fold higher and acrolein emissions up to 8-fold higher, frequently exceeding short-term exposure limits. Aromatic aldehydes and alcohols also increased emissions, though to a lesser extent, while esters showed smaller or inconsistent effects. The influence of flavors was further modulated by their concentration, PG/VG ratio, and device power, with higher concentration, VG content, and power amplifying emissions. These results highlight the complex interactions among e-liquid composition, flavor class, and vaping conditions, demonstrating that certain flavorings substantially elevate toxicant emissions. These findings underscore the importance of considering flavor composition, device power, and base material in evaluating the potential health risks associated with e-cigarette use.

Hydroxyacetone was previously detected at high concentrations (up to ∼12 mg/mL) in electronic cigarette (EC) aerosols, including those derived from products associated with adverse health effects. Given the limited understanding of its inhalation toxicology, we investigated hydroxyacetone's impact on human airway epithelial cells. Acute exposures at the air-liquid interface (ALI) using 3D EpiAirway tissues─a surrogate for human tracheobronchial epithelium─were analyzed via proteomics. Differential expression analysis identified numerous affected proteins, with enrichment pointing to alterations in mitochondrial function and actin cytoskeletal disruption as major targets. Ingenuity Pathway Analysis (IPA) highlighted "Mitochondrial Dysfunction" and "NRF2-Mediated Oxidative Stress" among top toxicological categories, and "Nuclear Cytoskeletal Signaling" as a key canonical pathway. To validate and extend these findings, submerged cultures of BEAS-2B cells were exposed to hydroxyacetone (0.01-10 mg/mL) and assessed for mitochondrial activity, oxidative stress, and F-actin integrity. At 1 mg/mL, mitochondrial membrane potential and reactive oxygen species (ROS) increased, with elevated hydrogen peroxide detected in the culture medium. At 10 mg/mL, mitochondrial activity declined significantly, accompanied by cell rounding and apoptotic blebbing within 2 h. F-actin destabilization occurred at 1, 3.33, and 10 mg/mL, with cytoplasmic and perinuclear filaments more affected than cortical actin. Findings from ALI and submerged models were concordant, supporting hydroxyacetone-induced mitochondrial stress, oxidative damage, and cytoskeletal disruption. These results suggest that hydroxyacetone concentrations found in EC aerosols may contribute to respiratory toxicity and warrant further investigation.

Fine particulate matter (PM2.5) is a complex mixture of air pollutants that may contain hazardous substances and emerging contaminants. It penetrates deep into the lungs, inducing oxidative stress, inflammation, and systemic toxicity, and interacts with O3, NO2, SO2, and organic and inorganic constituents, thereby increasing health risks.

Comparative toxicological studies of heterogeneous particulate matter (PM) samples are needed to evaluate the influence of particle chemistry on pulmonary toxicity outcomes. Here, groups of mice were exposed by oropharyngeal aspiration of a 100 μg dose of one of seven PM samples, including three coarse and two fine ambient air PM, and 2 fine emission source PM. Acute inflammatory and lung injury markers in the bronchoalveolar lavage fluid (BALF) were assessed. A weighted chemical correlation network analysis (WCCNA) clustered PM chemical constituents into four modules based on comodulation within samples. These modules and their components were then correlated with lung toxicity end points. One module represented the highest levels of zinc, lead, copper, and tin, and was strongly correlated with BALF neutrophils, macrophage inflammatory protein-2, and several markers of lung injury. A second module represented the highest levels of several toxic transition metals including magnesium, nickel, vanadium, and cobalt, and was strongly correlated with pro-inflammatory interleukin-6, in addition to neutrophils, albumin, and lactate dehydrogenase. A third module, represented by high levels of elemental carbon, nitrate, sulfate, and phosphate, was correlated with pro-inflammatory tumor necrosis factor-α (TNF-α), in addition to BALF protein and other lung injury markers. The final module consisted of 7 elements associated with the 3 coarse crustal PM samples, and these individual elements exhibited moderate correlations with BALF neutrophils and TNF-α. Toxic transition metals produced the greatest effects on lung toxicity, followed by anions and carbon species. These studies demonstrated that chemical and toxicological assessments of heterogeneous samples of PM produce clusters of chemical constituents that can be correlated with separate toxicological outcomes.

Perfluorohexyloctane (F6H8) is a semifluorinated alkane increasingly used in medical applications. Emerging evidence, however, indicates that this compound can persist in biological systems and influence cellular processes. These observations suggest that the exceptional stability of F6H8, while beneficial for medical performance, may also have implications for long-term biological and health outcomes.