The widespread use and poor management of single-use plastics have created a global pollution issue with emerging human health concerns. Environmental degradation of plastics produces micro- and nanometer-sized particles that may become airborne and inhaled. While some are removed by lung defenses, others persist and trigger inflammation or toxic effects, including reproductive harm, carcinogenicity, and mutagenicity. Because airborne microplastics are often fibrous, this study focuses on how size, shape, and orientation influence their deposition. Deposition fractions of microplastic fibers in different regions of the human lung were estimated using the International Commission on Radiological Protection (ICRP) deposition model, with adjustments for fiber geometry, density, and orientation through aerodynamic and volume-equivalent diameters. Fiber lengths of 10-50 µm and diameters of 0.75-5 µm, representative of airborne microplastics reported in environmental samples, were modeled under parallel, perpendicular, and random orientations to evaluate regional deposition patterns. From our modeling results, the maximum deposition fraction was approximately 0.87 in the nasopharyngeal region for fibers with aerodynamic diameters of ~5-7 µm, whereas in the alveolar region, the highest deposition fraction was 0.13 for fibers with diameters of 0.75 µm and lengths up to 35 µm, with these outcomes predicted under random orientation conditions. This study provides the first systematic modeling of lung deposition for fibrous microplastics as a function of size, shape, density, and orientation, offering novel equations and predictive curves that can be directly utilized in inhalation exposure and human health risk assessment.

Bisphenol A (BPA) has been strictly regulated worldwide due to its well-documented adverse health effects, prompting the widespread use of structural analogs such as bisphenol AF (BPAF) and bisphenol fluorene (BHPF). Emerging evidence shows that these substitutes also exhibit estrogenic activity, challenging their presumed safety. However, the molecular mechanisms underlying their modulation of estrogen receptors (ERs) remain largely unknown. Addressing this gap is critical for accurate risk assessment and the development of safer alternatives. Herein, we employed computational toxicology approaches to elucidate the interaction mechanisms of BPAF and BHPF with ER alpha (ERα), a central regulator of endocrine function and breast cancer progression. Our results showed that BHPF displays the greatest estrogenic potency among the tested compounds. Molecular interaction analyses revealed that hydrophobic interactions, especially the van der Waals force, rather than hydrogen bonding, predominantly govern the binding of the two bisphenol derivatives (BPs) to ERα. Notably, the rigid fluorenyl ring structure of BHPF markedly enhances van der Waals interactions, resulting in more stable ER binding and suggesting potential for high biological retention and cumulative risk. Consistently, toxicological assessments indicated that BHPF poses elevated health risks to the lungs and gastrointestinal system. By contrast, BPAF, with its flexible scaffold, exhibited more diverse binding interactions. It exhibits stronger organ-specific toxicity, notably affecting the cardiovascular system and kidneys. This study provides molecular-level insight into the binding mechanisms of BPs with ERα, offering theoretical support for understanding their potential endocrine-disrupting effects and informing environmental health risk assessments.

Fine particulate matter (PM_2.5) exposure has been recognized as one of the risk factors for chronic obstructive pulmonary disease (COPD). With increased PM_2.5-related research, the mechanism of PM_2.5-induced toxicity suggests the role of non-coding RNA (ncRNA) in this process; however, a comprehensive framework to link PM_2.5 exposure with COPD remains vacant. The adverse outcome pathway (AOP) framework integrates research from different models to achieve a systematic assessment of PM_2.5 toxicity in the respiratory system. This review focused on PM_2.5-related pathology of COPD at molecular, cellular, organic, individual and population levels using the AOP framework. Combined with our previous studies, the AOP-Wiki website, and other available evidence, we established an AOP framework in which the molecular initiating event is the alteration of ncRNA expression profiles. Subsequently, oxidative stress and activation of the inflammatory pathway induced pulmonary inflammation, epithelial-mesenchymal transition, fibroblast proliferation, and myofibroblast differentiation, leading to airway remodeling, pulmonary epithelial cell apoptosis, and emphysema caused by autophagy. These were identified as key events. They collectively contribute to the pathogenesis of COPD by altering the structure and function of the airways and lung tissue, thus exacerbating respiratory symptoms and disease progression. This framework will provide a reference to identify biomarkers of PM_2.5 exposure-triggered respiratory diseases.

Organophosphate esters (OPEs), commonly employed as flame retardants and plasticizers, have raised increasing concern due to their potential impacts on human health. Despite their widespread use, population-based evidence regarding their relationship with sleep health remains scarce. In this research, we examined data from the 2013-2016 cycles of the U.S. National Health and Nutrition Examination Survey (NHANES) to investigate the relationship between urinary OPE metabolites and sleep outcomes. The analysis included 2,606 participants who had complete data on both exposure and outcomes. Multivariable linear and logistic regression models were applied to examine associations, while restricted cubic spline models were used to test for potential nonlinear dose-response patterns. To account for combined exposure, we further conducted Bayesian kernel machine regression and weighted quantile sum regression. Our findings showed that dibutyl phosphate (DBUP) was inversely related to sleep duration and exhibited nonlinear associations with sleep indicators. Mixed-exposure analyses indicated that higher cumulative levels of OPEs were linked to shorter sleep duration. Additionally, bis(1-chloro-2-propyl) phosphate (BCPP) was positively related to self-reported sleep problems, particularly among older participants. In general, the findings indicate that exposure to OPEs, particularly DBUP (which originates from tri-n-butyl phosphate, TNBP) and BCPP [derived from tris(2-chloro-isopropyl) phosphate, TCPP], may be associated with sleep disturbances among the U.S. population. Additional mechanistic and long-term studies are needed to validate these associations.

Landfills are the main storage facilities for plastic waste, which is prone to degradation into microplastics and potential transference to surrounding areas. This study focused on the characteristics and potential risks of microplastics in soil near the Anyang landfill in China, the largest municipal waste disposal facility in the area. Receiving plastic-rich domestic waste makes this landfill a potential source of microplastic pollution to the surrounding environment. Microplastics were extracted via density separation and the oxidative digestion method. Their abundance, morphological traits, and types were analyzed through microscopy and infrared spectroscopy. This study conducted further research on the link between microplastic levels and soil physicochemical properties, and the associated ecological risks. The findings indicated that the abundance of microplastics in the soil varied between 900 and 4,900 items/kg. The majority of microplastics measured were smaller than 0.5 mm. The main shapes of microplastics included fibers, films, and fragments. Seven colors of microplastics were identified, with black accounting for the highest proportion. Rayon and polypropylene were the major polymer types. Microplastic abundance showed no significant correlation with soil organic matter content, pH, or electrical conductivity, but was significantly influenced by soil texture. Overall, the microplastic pollution level in the study area was classified as moderate, and the potential ecological risk was low. These findings suggested that microplastic pollution in soils near landfills may be influenced by landfill waste. This study provided a valuable reference for evaluating the soil microplastic pollution status, ecological risks, and pollution prevention and control near the landfill site in Anyang City.

Cigarette smokers are exposed to over 7,000 chemicals, including many toxic and carcinogenic agents. Alternative non-combustible nicotine products considerably reduce exposure to harmful constituents. Extensive research on biomarkers of potential harm is crucial for assessing the early health impacts of smoking and the reduction of harm after quitting or switching to alternative products. However, such clinical trials are constrained by poor verification of self-reported product use, as common procedures using exhaled carbon monoxide (eCO) and cotinine strip tests are limited by short detection periods and non-specificity, respectively. Therefore, product-use-specific biomarkers of exposure (BoEs) are needed for accurate biochemical verification in studies evaluating the health impact of new products, such as electronic cigarettes. We conducted a cross-sectional study in 180 participants, including current, former, and never-smokers, and applied several BoEs to verify their use behavior. Our multi-biomarker approach monitored exposure to nicotine, tobacco-specific nitrosamines, acrylonitrile and propylene glycol (PG), which were significantly elevated in the current smoker group except PG, identifying six non-compliant subjects (4 current, 1 former and 1 never-smoker). The proposed biomarker panel outperformed eCO and was able to distinguish distinct use patterns, such as vaping vs. smoking, thereby enhancing data accuracy. Moreover, biochemically determined exposure variables such as carboxyhemoglobin and cotinine showed stronger correlations with BoEs than self-reported cigarette consumption. Therefore, the suggested panel is particularly valuable for non-controlled studies, where reliance on self-report can bias outcomes. Implementing the proposed verification strategy can improve study validity and strengthen evidence on the health impacts of switching to alternative products.

As an emerging environmental pollutant, micro/nanoplastics (MNPs) have been reported to accumulate in brain tissues, which may lead to risks of neurotoxicity in humans. Current traditional neurotoxicity models face difficulties in species differences and ethical limitations, whereas brain organoids derived from human cells can simulate the complex structure and function of the human brain, providing a novel model for studying the neurotoxicity of MNPs. In this study, we have reviewed the progress in applying brain organoids to assess the health risks of environmental pollutants including MNPs. MNPs can penetrate into brain organoids and cause toxic effects such as mitochondrial dysfunction, calcium signaling disruption, and abnormal neural differentiation, which may promote pathological phenotypes associated with neurodegenerative diseases. These findings are usually obtained from organoids derived from human-induced pluripotent stem cells, whereas models derived from human embryonic stem cells still require further exploration. Future perspectives are also proposed for technological innovation in brain organoids, including developing region-specific brain organoids, fetal brain organoids, and standardized brain organoid platforms to facilitate their broader application in environmental neurotoxicity assessment of environmental pollutants.

The 6-PPD quinone (6-PPDQ) is frequently detected in environment. However, the possible effect of 6-PPDQ on amino acid metabolism and corresponding mechanisms remain unclear. In Caenorhabditis elegans, we examined effect of 6-PPDQ exposure on the absorption and catabolism of arginine. In nematodes, 6-PPDQ exposure reduced arginine content, and decreased expression of amino acid transporter 1 (aat-1) and C50D2.2 encoding intestinal transporters. Intestinal RNA interference (RNAi) of aat-1 and C50D2.2 reduced arginine content. Additionally, 6-PPDQ increased the expression of slc-25A29, which governs arginine import into the mitochondria, and argn-1, which governs mitochondrial arginine catabolism. Arginine content was increased by slc-25A29 and argn-1 RNAi. 6-PPDQ-induced mitochondrial dysfunction was strengthened by aat-1 and C50D2.2 RNAi and suppressed by slc-25A29 and argn-1 RNAi. The expression of slc-25A29 and argn-1 was further increased by RNAi of aat-1 and C50D2.2, and in the mitochondria, gas-1, mev-1, sod-3, and hsp-6 were identified as targets of argn-1 for controlling 6-PPDQ toxicity. Therefore, exposure risk of 6-PPDQ in disrupting arginine absorption and catabolism was suggested, which was associated with 6-PPDQ-induced mitochondrial dysfunction.

Antibiotics are widely detected in aquatic environments; however, ecological water quality criterias (WQCs) and human health-based limits, such as maximum residue limits, are derived under separate regulatory frameworks, potentially leaving gaps in achieving integrated One Health protection. Here, we propose a complementary approach that integrates ecological processes, including bioaccumulation and trophic transfer, with food safety-based human exposure limits to evaluate health-protective environmental thresholds. Using trimethoprim as a proof of concept, we illustrate how food safety limits for aquatic products can be translated into organism-level thresholds and further linked to water-phase concentrations using reported bioaccumulation factors. The resulting threshold range is substantially lower than the conventional species sensitivity distribution-derived WQC, suggesting that ecotoxicity-based criteria alone may underestimate risks associated with human dietary exposure. Rather than replacing existing WQCs, this framework provides an additional line of evidence for comparing thresholds and identifying the more protective values. By explicitly linking environmental contamination, ecological processes, and human dietary exposure, this approach offers a practical pathway for operationalizing One Health principles in environmental risk management.

Nanoplastics, an emerging class of environmental contaminants, have become a growing concern due to their widespread distribution and potential to interfere with cellular and tissue homeostasis. The liver, as a primary site of xenobiotic metabolism and clearance, is particularly vulnerable to nanoplastic exposure. Hepatic stellate cells (HSCs) play a central role in maintaining liver extracellular matrix (ECM) homeostasis and in initiating fibrogenic responses; therefore, understanding how nanoplastics affect HSC behavior is critical for elucidating early mechanisms of nanoplastic-induced liver injury. To achieve physiologically relevant modeling, we employed HSC and collagen hydrolysate to construct a simplified matrix–cell–matrix mimicking the microenvironment of the hepatic space of Disse, we found that both aminated (PS-NH₂) and carboxylated (PS-COOH) polystyrene nanoplastics were retained within collagen hydrolysate matrices and altered their viscoelastic properties, with more significantly negatively charged PS-COOH increasing matrix viscosity. HSCs cultured within PS-COOH–treated matrices exhibited enhanced proliferation and migration without apparent cytotoxicity, accompanied by intensified F-actin stress fiber formation and nuclear translocation of the mechanosensitive coactivator yes-associated protein (YAP). Together, these findings indicate that nanoplastics may indirectly activate quiescent HSCs by remodeling ECM mechanical properties, rather than through direct cellular uptake. This work provides a mechanobiological perspective linking environmental nanoplastic exposure to early hepatic fibrogenesis.

Infants are particularly vulnerable to the adverse effects of persistent organic pollutants (POPs) due to their developing physiological systems and relatively high exposure per unit body weight. This study quantified legacy POPs in breast milk samples collected from 99 lactating mothers in Wuhan, China, and evaluated their associations with neonatal birth outcomes. The predominant organochlorine pesticides (OCPs) detected were 1,2,3,4,5,6-hexachlorocyclohexanes (HCHs) and dichlorodiphenyltrichloroethane (DDT) metabolites. Among polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), PCB-52 and BDE-154 were the most abundant congeners. Maternal factors, including parity, body mass index, and dietary patterns, significantly influenced POP concentrations in breast milk. Our results revealed significant associations between specific POPs and birth outcomes. For instance, β-HCH was positively correlated with birth weight, whereas heptachlor exhibited a negative correlation. Additionally, PCB-170 was inversely correlated with infant head circumference, while BDE-28 and BDE-99 showed positive correlations. Our health risk assessment demonstrated that, despite elevated POP levels in a subset of samples, the estimated daily intake for most breastfed infants remained below established safety thresholds. These findings reaffirm that the established nutritional and immunological benefits of breastfeeding far outweigh the potential risks from background POP exposure. Nevertheless, the persistent and widespread detection of these contaminants underscores the need for ongoing biomonitoring and public health interventions to reduce maternal body burdens by mitigating environmental and dietary sources.