Electronic cigarettes (ECs) are purported to be tobacco harm-reduction products whose degree of harm has been highly debated. EC use is considered less hazardous than smoking but is not expected to be harmless. Following the banning of e-liquid flavors in countries such as the US, Finland, Ukraine, and Hungary, there are growing concerns regarding the safety profile of e-liquid flavors used in ECs. While these are employed extensively in the food industry and are generally regarded as safe (GRAS) when ingested, GRAS status after inhalation is unclear. The aim of this review was to assess evidence from 38 reports on the adverse effects of flavored e-liquids on the respiratory system in both in vitro and in vivo studies published between 2006 and 2021. Data collected demonstrated greater detrimental effects in vitro with cinnamon (9 articles), strawberry (5 articles), and menthol (10 articles), flavors than other flavors. The most reported effects among these investigations were perturbations of pro-inflammatory biomarkers and enhanced cytotoxicity. There is sufficient evidence to support the toxicological impacts of diacetyl- and cinnamaldehyde-containing e-liquids following human inhalation; however, safety profiles on other flavors are elusive. The latter may result from inconsistencies between experimental approaches and uncertainties due to the contributions from other e-liquid constituents. Further, the relevance of the concentration ranges to human exposure levels is uncertain. Evidence indicates that an adequately controlled and consistent, systematic toxicological investigation of a broad spectrum of e-liquid flavors may be required at biologically relevant concentrations to better inform public health authorities on the risk assessment following exposure to EC flavor ingredients.

Concerns have been expressed that inhaled nanoparticles may behave differently to larger particles in terms of lung clearance and translocation, with potential implications for their toxicity. Studies undertaken to investigate this have typically involved limited post-exposure periods. There is a shortage of information on longer-term clearance and translocation patterns and their dependence on particle size, which this study aimed to address. Rats were exposed (<3 h) nose-only to aerosols of spark-generated radioactive iridium-192 nanoparticles of four sizes: 10 nm, 15 nm, 35 nm and 75 nm (count median diameter) (aerosol mass concentrations 17, 140, 430, and 690 μg/m3, respectively). The content of iridium-192 in the whole animal, organs, tissues, and excreta was measured at various times post-exposure to ≥ 1 month. Limited toxicological investigations were undertaken for the 10 nm aerosol using bronchoalveolar lavage fluid. Elemental maps of tissue samples were produced using laser ablation inductively coupled plasma mass spectrometry and synchrotron micro-focus x-ray fluorescence. The chemical speciation of the iridium was explored using synchrotron micro focus x-ray near-edge absorption spectroscopy. Long-term lung retention half-times of several hundred days were found, which were not dependent on particle size. There was significant variation between individual animals. Analysis of bronchoalveolar lavage fluid for the 10 nm aerosol indicated a limited inflammatory response resolving within the first 7 days. Low levels of, particle size dependent, translocation to the kidney and liver were found (maximum 0.4% of the lung content). Any translocation to the brain was below the limits of detection (i.e. < 0.01% of the lung content). The kidney content increased to approximately 30 days and then remained broadly constant or decreased, whereas the content in the liver increased throughout the study. Laser ablation inductively coupled plasma mass spectrometry analysis indicated homogeneous iridium distribution in the liver and within the cortex in the kidney. Slow lung clearance and a pattern of temporally increasing concentrations in key secondary target organs has been demonstrated for inhaled iridium aerosol particles < 100 nm, which may have implications for long-term toxicity, especially in the context of chronic exposures.

Nanomaterial inhalation represents a potential hazard for respiratory conditions such as asthma. Cerium dioxide nanoparticles (CeO2NPs) have the ability to modify disease outcome but have not been investigated for their effect on models of asthma and inflammatory lung disease. The aim of this study was to examine the impact of CeO2NPs in a house dust mite (HDM) induced murine model of asthma. Repeated intranasal instillation of CeO2NPs in the presence of HDM caused the induction of a type II inflammatory response, characterised by increased bronchoalveolar lavage eosinophils, mast cells, total plasma IgE and goblet cell metaplasia. This was accompanied by increases in IL-4, CCL11 and MCPT1 gene expression together with increases in the mucin and inflammatory regulators CLCA1 and SLC26A4. CLCA1 and SLC26A4 were also induced by CeO2NPs + HDM co-exposure in air liquid interface cultures of human primary bronchial epithelial cells. HDM induced airway hyperresponsiveness and airway remodelling in mice were not altered with CeO2NPs co-exposure. Repeated HMD instillations followed by a single exposure to CeO2NPs failed to produce changes in type II inflammatory endpoints but did result in alterations in the neutrophil marker CD177. Treatment of mice with CeO2NPs in the absence of HDM did not have any significant effects. RNA-SEQ was used to explore early effects 24 h after single treatment exposures. Changes in SAA3 expression paralleled increased neutrophil BAL levels, while no changes in eosinophil or lymphocyte levels were observed. HDM resulted in a strong induction of type I interferon and IRF3 dependent gene expression, which was inhibited with CeO2NPs co-exposure. Changes in the expression of genes including CCL20, CXCL10, NLRC5, IRF7 and CLEC10A suggest regulation of dendritic cells, macrophage functionality and IRF3 modulation as key early events in how CeO2NPs may guide pulmonary responses to HDM towards type II inflammation. CeO2NPs were observed to modulate the murine pulmonary response to house dust mite allergen exposure towards a type II inflammatory environment. As this type of response is present within asthmatic endotypes this finding may have implications for how occupational or incidental exposure to CeO2NPs should be considered for those susceptible to disease.

Incidents involving the release of chemical agents can pose significant risks to public health. In such an event, emergency decontamination of affected casualties may need to be undertaken to reduce injury and possible loss of life. To ensure these methods are effective, human volunteer trials (HVTs) of decontamination protocols, using simulant contaminants, have been conducted. Simulants must be used to mimic the physicochemical properties of more harmful chemicals, while remaining non‐toxic at the dose applied. This review focuses on studies that employed chemical warfare agent simulants in decontamination contexts, to identify those simulants most suitable for use in HVTs of emergency decontamination. Twenty‐two simulants were identified, of which 17 were determined unsuitable for use in HVTs. The remaining simulants (n = 5) were further scrutinized for potential suitability according to toxicity, physicochemical properties and similarities to their equivalent toxic counterparts. Three suitable simulants, for use in HVTs were identified; methyl salicylate (simulant for sulphur mustard), diethyl malonate (simulant for soman) and malathion (simulant for VX or toxic industrial chemicals). All have been safely used in previous HVTs, and have a range of physicochemical properties that would allow useful inference to more toxic chemicals when employed in future studies of emergency decontamination systems.

Planning for major incidents involving the release of hazardous chemicals has been informed by a multi-disciplinary research agenda which has sought to inform all aspects of emergency response, but with a focus in recent years on mass casualty decontamination. In vitro and human volunteer studies have established the relative effectiveness of different decontamination protocols for a range of chemical agents. In parallel, a programme of research has focused on communicating with and managing large numbers of contaminated casualties at the scene of an incident. We present an accessible overview of the evidence underpinning current casualty decontamination strategies. We highlight where research outcomes can directly inform response planning, including the critical importance of beginning the decontamination process as soon as possible, the benefits of early removal of contaminated clothing, the evidence under-pinning dry and wet decontamination and how effective communication is essential to any decontamination response. We identify a range of priority areas for future research including establishing the significance of the ‘wash-in’ effect and developing effective strategies for the decontamination of hair. We also highlight several areas of future methodological development, such as the need for novel chemical simulants. Whilst considerable progress has been made towards incorporating research outcomes into operational policy and practice, we outline how this developing evidence-base might be used to inform future iterations of mass casualty decontamination guidance.