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.

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.