Polystyrene microplastics (PS–MPs) are emerging environmental pollutants with growing evidence of neurotoxic effects. This study examined how particle size and surface charge influence PS–MPs-induced neurotoxicity in male mice. Chronic exposure to 5000 nm PS–MPs disrupted excitatory–inhibitory balance in the basolateral amygdala, marked by upregulation of excitatory markers (VGLUT2, GLUA1) and downregulation of inhibitory markers (GAD65 + 67, GABABR1). These synaptic alterations were accompanied by glial activation, neuroinflammation, and microglial polarization toward a pro-inflammatory M1 state (CD86/CD206). In vitro co-culture and conditioned media experiments confirmed that microglial activation contributes to astrocytic and neuronal injury independent of direct PS–MPs internalization. Statistical modeling encompassing principal component analysis and multiple linear regression identified surface charge (zeta potential) as a stronger predictor than particle size for neuroinflammatory and behavioral outcomes, although size more directly influenced glial activation. Contrary to the assumption that smaller particles are inherently more toxic due to greater uptake, 5000 nm PS–MPs induced more severe neurotoxic effects, likely through microenvironmental disruption rather than cellular internalization. These findings underscore that PS–MPs neurotoxicity is driven by a complex interplay between particle size and surface charge, with surface charge emerging as the dominant factor in driving microglial-mediated inflammation and behavioral changes. Overall, the study reveals that PS–MPs exposure disrupts neural signaling, triggers neuroinflammation, and promotes anxiety-like behaviors through glial activation and excitatory-inhibitory imbalance. These findings underscore the distinct and complementary roles of size and surface charge in PS–MPs neurotoxicity and highlight the importance of glial-mediated mechanisms in driving behavioral and neural circuit disruptions. Not applicable.
Zinc oxide nanoparticles (ZnO NPs) are widely used in consumer and biomedical products due to their antimicrobial activity and favorable biocompatibility. Although dermal exposure to ZnO NPs is generally considered safe, penetration beyond the skin barrier may occur under inflammatory or barrier-compromised conditions. However, the immunotoxicological consequences of ZnO NP exposure, particularly their effects on adaptive immune regulation during allergic inflammation, remain incompletely understood. Using ovalbumin (OVA)-induced murine models of delayed-type hypersensitivity (DTH) and atopic dermatitis (AD), we demonstrated that the immunomodulatory effects of ZnO NPs were highly dependent on the route of exposure. Among pharyngeal aspiration, intravenous, and subcutaneous administration, only subcutaneous exposure significantly exacerbated antigen-driven cutaneous inflammation. In both models, ZnO NPs treatment enhanced immune cell infiltration, promoted mast cell degranulation, and amplified antigen-specific humoral responses. Notably, ZnO NPs markedly increased CD4+ T cell accumulation in inflamed skin without altering intrinsic cytokine polarization. Mechanistically, ZnO NPs released Zn²⁺ ions, leading to intracellular reactive oxygen species (ROS) generation in T cells and subsequent activation of NF-κB (p65), p38, and c-Jun N-terminal kinase (JNK) signaling pathways. This ROS-dependent signaling cascade upregulated the skin-homing chemokine receptors C-C motif chemokine receptor 4 (CCR4), CCR8, and CCR10. Consistent with these changes, ZnO NP-treated T cells exhibited enhanced chemokine-directed migration in vitro. These findings demonstrate that subcutaneous exposure to ZnO NPs promotes local immune alterations in allergic skin, characterized by increased inflammatory cell infiltration and accumulation of CD4+ T cells. ZnO NP-derived Zn²⁺ induces ROS-dependent activation of NF-κB and mitogen-activated protein kinase (MAPK) signaling, leading to the upregulation of skin-homing chemokine receptors. Together with the enhanced chemokine-directed migration observed in vitro, these findings indicate that ZnO NP exposure alters T cell homing-related responses. These homing-related alterations represent an underappreciated aspect of nanoparticle immunotoxicity and highlight the need to consider tissue-specific immune dynamics when assessing the safety of ZnO NPs, particularly under conditions of skin inflammation or barrier disruption.
Household wood-burning is common in the U.S. Mountain West, yet it remains unknown whether typical U.S. exposure increases lung black carbon deposition or genomic instability. We conducted a multi-site pilot panel study of 109 woodstove users in New Mexico (NM), Alaska, Idaho, and Montana (2022–2024) during high-heating (greatest heating demand) and low-heating (mild heating demand) seasons. The NM site additionally included a non-heating season (no heating demand) and a comparison group of non-woodstove users (n = 18) assessed during the high-heating season. Key study elements includes indoor PM2.5, wood-burning behaviors, macrophage carbon load, and blood biomarkers of genomic instability. NM homes using wood-burning stoves had significantly higher indoor PM2.5 during the high-heating season (21.95 µg/m³) than during the non-heating season (4.10 µg/m³, p = 0.039) or non-woodstove homes during the high-heating season (3.79 µg/m³, p = 0.018). Moreover, woodstove users in NM had three-fold higher numbers of particles (NoP) in airway macrophages in high-heating season (1.88) than in non-heating season (0.61, P = 0.014) or non-users in high-heating season (0.79, p = 0.05). Those who routinely tended woodstoves showed higher area of particles (AoP) and percentages of cell occupied by carbons (PCOC) across all four sites (p < 0.05) and higher urinary levoglucosan in NM (0.23 versus 0.14 µg/g creatinine, p = 0.027) than those who never/seldomly did. Older woodstoves (≥ 20 years) were consistently associated with higher AoP, NoP, and PCOC. In NM, blood from woodstove users exhibited significantly higher frequencies of micronuclei, nuclear buds, and nucleoplasmic bridges. For example, micronuclei frequency increased from 14.46 in non-heating season to 23.08 per 1000 binucleated cells in high-heating season (p < 0.001). Overall, household wood-burning increases indoor PM2.5, lung-deposited black carbon, and genomic instability among the U.S. Mountain West residents. Replacing woodstoves older than 20 years and improving stove-tending practices may be promising intervention targets. Not applicable.
Occupational exposure to nanoparticles occurs across diverse industrial sectors. Preclinical studies indicate that such exposures may pose health risks. However, characterization of these risks in real-world occupational-environments remains limited. This scoping review summarizes the evidence on health effects associated with occupational exposure to nanomaterials and ultrafine particles (UFP), the diagnostic approaches for early detection of health effects, and to identify knowledge gaps. A comprehensive search was conducted in MEDLINE, EMBASE, and Web of Science from inception to April 2024. Peer-reviewed studies that assessed health outcomes among workers exposed to nanomaterials or UFP in occupational-settings were included. No appraisal of quality was performed. Of 6,020 unique records, 66 studies met inclusion criteria, mostly cross-sectional (n = 37) or panel studies (n = 18). Nanomaterials exposures included carbon nanotubes/fibers, titanium dioxide, and metal oxides mainly in manufacturing and processing industries. Studies reported pulmonary and cardiovascular outcomes along with effects on systemic biomarkers of cellular stress and molecular alterations. Pulmonary outcomes included affected lung function and increased levels of markers of inflammation and oxidative stress. Cardiovascular outcomes mainly included elevated markers of endothelial dysfunction, cardiac autonomic dysregulation, hypercoagulation, and vascular inflammation. Systemic biomarkers included immune alterations, oxidative stress, DNA damage, and epigenetic alterations. Multiple diagnostic approaches demonstrate strong potential for early detection of nanoparticles-related adverse health outcomes in occupational health. Current evidence indicates that occupational exposure to nanoparticles may be linked with pulmonary and cardiovascular outcomes, together with alterations in systemic biomarkers. Various diagnostic methods have been reported with potential for early detection of adverse health outcomes in occupational health. However, evidence is largely based on cross-sectional and small-scale studies, with considerable heterogeneity in exposure assessment and outcome definitions. Longitudinal studies with standardized exposure characterization and harmonized diagnostic protocols are needed to establish causality and improve risk assessment in occupational settings. Not applicable.
The detection of micro- and nanoplastics (MNPs) in the human brain is a critical frontier in neurotoxicology, yet analysis is severely hindered by the brain’s complex, lipid-rich matrix. Recent concerns regarding “false positive” signals from endogenous fats necessitate the development of rigorous, validatable pretreatment protocols. This study optimized pretreatment procedures for post-mortem human dorsal thalamus samples. We compared oxidative (H₂O₂), alkaline-oxidative (NaOH/H₂O₂), and acidic microwave-assisted (HNO₃) digestion. MNP presence and polymer integrity were cross-validated using a multi-analytical suite: Laser Direct Infrared (LDIR) imaging, Optical Photothermal Infrared (O-PTIR) spectroscopy, SEM-EDS, and MALDI-TOF MS. Lipid removal efficiency was quantitatively assessed via GC-MS. Standard oxidative or alkaline digestions were found insufficient, as they promote the formation of insoluble zinc and calcium lipid salts (soaps) that mimic polymer spectra. A critical methodological advancement was achieved by incorporating an ethanol-assisted solvent stage and a 5
