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.