Nerve agent poisoning is often linked with mass-casualty events. Typical examples are battlefield use or large terrorist attacks. However, documented incidents from the last decades show a broader and more complex picture. The perspective follows a line of documented cases. It starts with the 1978 ricin “umbrella” murder of Georgi Markov in London (non-nerve agent attack, but historically important). It then moves to the sarin attacks in Matsumoto (1994) and the Tokyo subway (1995), the VX assassinations by the Aum Shinrikyo cult (1994–1995), the 2013 sarin attack in Ghouta and the recent targeted poisonings of Kim Jong-nam (2017), Sergei and Yulia Skripal (2018), Dawn Sturgess and Charlie Rowley (2018) and Alexei Navalny (2020). We use these cases to show how route of exposure, dose, formulation and environmental persistence shape toxicokinetics, clinical presentation, biomarker formation and forensic interpretation. For each case we give the circumstances, the agent, the route, the clinical course, the treatment and the forensic confirmation in detail. We focus on acetylcholinesterase and butyrylcholinesterase inhibition, aging, protein adduct formation, dermal absorption and environmental persistence. We describe a recurring “toxicological paradox”: greater control over exposure can reduce immediate lethality, but at the same time it increases diagnostic uncertainty and forensic complexity. The cases also show that mass and targeted use are not two separate historical stages. They coexist within the same period, sometimes even within one perpetrator organisation. This perspective has direct implications for emergency preparedness, biomarker development, antidotal treatment windows and international chemical incident response.
Nanoscale processing enhances the photocatalytic reactivity of titanium dioxide nanoparticles (TiO2 NPs) under UV exposure. While these nanoparticles are widely utilized in cosmetics and industrial formulations, the molecular decision-making processes that dictate keratinocyte survival following UV exposure remain poorly understood. Here, we demonstrate that concurrent exposure to TiO2 NPs and UVA radiation induces substantial synergistic phototoxicity, which does not occur under individual exposure at the same respective doses. Under phototoxic conditions, keratinocytes were found to engage an adaptive response characterized by G3BP1-dependent stress granule (SG) assembly to mitigate cellular stress. Mechanistically, this cytoprotective response was driven by PERK/eIF2α signaling and coordinated by endoplasmic reticulum–mediated calcium flux. Pharmacological inhibition of SG assembly or genetic knockdown of G3BP1 exacerbated cell death, indicating that SG formation serves as a cytoprotective mechanism that relieves proteotoxic burden. Collectively, these findings delineate a proteostatic defense mechanism against TiO2-mediated phototoxicity, providing fundamental insights for the safe-by-design evaluation of advanced dermatological materials.
Sprenger et al. (2026) provide an extensive transcriptomic dataset covering 33 PFAS congeners in differentiated HepaRG cells and report broadly comparable molecular responses across structurally diverse substances. The dataset is valuable, but the cross-PFAS comparison requires a clearer distinction between relative concentration categories, numerical exposure concentrations and toxicological potency. For each PFAS, three non-cytotoxic concentrations were selected individually. The resulting numerical concentrations ranged from 5 to 250 µM. All 33 congeners were tested at 25 µM, 25 of 33 at 100 µM and 22 of 33 at 250 µM. Nevertheless, the subsequent comparative IPA analyses were based on the labels “low”, “medium” and “high”, rather than numerical concentrations. These labels therefore do not represent equivalent exposure intensities across PFAS. The distinction becomes consequential because the authors report concentration-dependent increases in differentially expressed genes for most compounds and because several additional pathways emerged predominantly at the high concentration, which was close to the cytotoxicity threshold for some PFAS but substantially below it for others. Thus, the high category can simultaneously encode chemical identity, nominal dose and position relative to cytotoxicity. This does not mean that category-based comparisons are invalid. Rather, they answer a narrower question: whether compounds perturb common pathways at their individually selected exposure levels. Concentration-resolved or potency-based analyses would complement this approach and help distinguish shared molecular response from comparable potency and from effects emerging only at different positions on the concentration-response continuum.
Rifampicin-associated liver volume changes in healthy volunteers provide an opportunity to examine the human relevance of xenobiotic-induced liver growth. This Comment considers three aspects of the clinical analysis relevant to interpreting the observed response. Clarification of whether the volumetric outcomes and choice of normalisation were prespecified, alongside paired treatment effects and confidence intervals, would help establish the basis for inference and assess the response’s magnitude and precision. For a small volumetric response, blinded repeat segmentation of existing magnetic resonance images and details of scan timing and pre-scan intake would help assess reproducibility under comparable physiological conditions. Associations between 4β-hydroxycholesterol and liver volume could also be examined using within-participant rifampicin-minus-placebo differences, with appropriate attention to the crossover design and an exploratory interpretation. Most of these suggestions could be addressed through protocol information and existing imaging and crossover data, strengthening interpretation of the human findings and guiding further investigation of pregnane X receptor-mediated liver growth.
As humans spend most of their time indoors, they are continuously exposed to an array of indoor air pollutants. While exposure to individual indoor air pollutants may often occur at low levels, cumulative exposure to indoor air pollutants contributes substantially to the human exposome. Chronic inhalation of indoor air pollutants has been associated with multiple respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and respiratory infections. In this study, the cellular effects of an acute indoor dust exposure using a three-dimensional airway epithelial model were investigated. Bronchial epithelial cells (16HBE14o-) were cultured as spheroids and exposed to reference indoor dust (SRM 2585; 0–200 µg/mL) for 24 h. Metabolic activity, intracellular reactive oxygen species (ROS) levels, inflammatory cytokine secretion, and secretome profiles were assessed. Indoor dust exposure did not induce morphological alterations or significant reductions in metabolic activity. Instead, a concentration-dependent increase in intracellular ROS was observed. Cytokine analysis revealed selective cytokine modulation, while untargeted proteomics identified limited changes in individual protein abundance. Instead, pathway-level analyses revealed enrichment of epithelial differentiation-related pathways. Overall, these findings suggest that a 24 h indoor dust exposure may elicit subtle cellular responses rather than overt cytotoxicity or inflammatory activation. This study highlights the applicability of integrating functional, immunological, and proteomics-based approaches with 3D airway models to investigate cellular responses to complex environmental particle mixtures. However, direct extrapolation to human exposure scenarios is limited by uncertainties regarding effective cellular dose, particle localization and environmental representativeness. Therefore, these findings should be interpreted as exploratory, hypothesis-generating observations.
