Identification and characterization of quaternary ammonium compounds in Flemish indoor dust by ion-mobility high-resolution mass spectrometry.

Quaternary ammonium compounds (QACs) are a class of surfactants commonly used in disinfecting and cleaning products. Their use has substantially increased during the COVID-19 pandemic leading to increasing human exposure. QACs have been associated with hypersensitivity reactions and an increased risk of asthma. This study introduces the first identification, characterization and semi-quantification of QACs in European indoor dust using ion-mobility high-resolution mass spectrometry (IM-HRMS), including the acquisition of collision cross section values (DTCCSN2) for targeted and suspect QACs. A total of 46 indoor dust samples collected in Belgium were analyzed using target and suspect screening. Targeted QACs (n = 21) were detected with detection frequencies ranging between 4.2 and 100 %, while 15 QACs showed detection frequencies > 90 %. Semi-quantified concentrations of individual QACs showed a maximum of 32.23 µg/g with a median ∑QAC concentration of 13.05 µg/g and allowed the calculation of Estimated Daily Intakes for adults and toddlers. Most abundant QACs matched the patterns reported in indoor dust collected in the United States. Suspect screening allowed the identification of 17 additional QACs. A dialkyl dimethyl ammonium compound with mixed chain lengths (C16:C18) was characterized as a major QAC homologue with a maximum semi-quantified concentration of 24.90 µg/g. The high detection frequencies and structural variabilities observed call for more European studies on potential human exposure to these compounds. For all targeted QACs, drift tube IM-HRMS derived collision cross section values (DTCCSN2) are reported. Reference DTCCSN2 values allowed the characterization of CCS-m/z trendlines for each of the targeted QAC classes. Experimental CCS-m/z ratios of suspect QACs were compared with the CCS-m/z trendlines. The alignment between the two datasets served as an additional confirmation of the assigned suspect QACs. The use of the 4bit multiplexing acquisition mode with consecutive high-resolution demultiplexing confirmed the presence of isomers for two of the suspect QACs.

[Migration, Transformation, and Toxicity of Quaternary Ammonium Antimicrobial Agents in the Environment].

Quaternary ammonium compounds (QACs) are one type of widely used cationic biocide, and their usage amount is growing rapidly due to the flu and COVID-19 pandemic. Many QACs were released into the environment in or after the course of their use, and thus they were widely detected in water, sediment, soil, and other environmental media. QACs have stronger surface activity and non-specific biotoxicity, which poses a potential threat to the ecosystem. In this study, the environmental fate and potential toxicity of QACs were documented in terms of their migration and transformation process, biological toxicity effects, and the main mechanisms of bacterial resistance to QACs. Aerobic biodegradation was the main natural way of eliminating QACs in the environment, and the reaction was mainly initiated by the hydroxylation of C atoms at different positions of QACs and finally mineralized to CO2and H2O through decarboxylation, demethylation, and ß-oxidation reaction. Toxicological studies showed that QACs at environmental concentrations could not pose acute toxicity to the selected biotas but threatened the growth and reproduction of aquatic organisms like Daphnia magna. Their toxicity effects depended on their molecular structure, the tested species, and the exposed durations. Additionally, our team first investigated the toxicity effects and mechanisms of QACs toward Microcystis aeruginosa, which showed that QACs depressed the algae growth through the denaturation of photosynthetic organelles, suppression of electron transport, and then induction of cell membrane damage. In the environment, the concentrations of QACs were always lower than their bactericidal concentrations, and their degradation could induce the formation of a concentration gradient, which facilitated microbes resistant to QACs. The known resistance mechanisms of bacteria to QACs mainly included the change in cell membrane structure and composition, formation of biofilm, overexpression of the efflux pump gene, and acquisition of resistance genes. Due to the similar targets and mechanisms, QACs could also induce the occurrence of antibiotic resistance, mainly through co-resistance and cross-resistance. Based on the existing data, future research should emphasize the toxicity effect and the potential QACs resistance mechanism of microorganisms in real environmental conditions.

Identifying environmental factors that influence immune response to SARS-CoV-2: Systematic evidence map protocol.

BACKGROUND: Widespread environmental contamination can directly interact with human immune system functions. Environmental effects on the immune system may influence human susceptibility to respiratory infections as well as the severity of infectious diseases, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Furthermore, the efficacy of vaccines to respiratory diseases may be impacted by environmental exposures through immune perturbations. Given the quick pace of research about COVID-19 and associated risk factors, it is critical to identify and curate the streams of evidence quickly and effectively. OBJECTIVE: We developed this systematic evidence map protocol to identify and organize existing human and animal literature on high-priority environmental chemical classes (Per- and polyfluoroalkyl substances, pesticides, phthalates, quaternary ammonium compounds, and air pollutants) and their potential to influence three key outcomes: (1) susceptibility to respiratory infection, including SARS-CoV-2 (2) severity of the resultant disease progression, and (3) impact on vaccine efficacy. The result of this project will be an online, interactive database which will show what evidence is currently available between involuntary exposures to select environmental chemicals and immune health effects, data gaps that require further research, and data rich areas that may support further analysis. SEARCH AND STUDY ELIGIBILITY: We will search PubMed for epidemiological or toxicological literature on select toxicants from each of the chemical classes and each of the three outcomes listed above. STUDY APPRAISAL AND SYNTHESIS OF METHODS: For each study, two independent reviewers will conduct title and abstract screening as well as full text review for data extraction of study characteristics. Study quality will not be evaluated in this evidence mapping. The main findings from the systematic evidence map will be visualized using a publicly available and interactive database hosted on Tableau Public.

Increased Use of Disinfectants During the COVID-19 Pandemic and Its Potential Impacts on Health and Safety

The COVID-19 pandemic has called for the increased use of disinfectants worldwide in public facilities, transportation, hospitals, nursing homes, wastewater treatment facilities, and even common households to mitigate virus burden. Active ingredients in common disinfectants recommended for use against COVID-19 viruses include chemicals such as quaternary ammonium compounds (QACs), hydrogen peroxide, bleach (sodium hypochlorite), and alcohols. These disinfecting chemicals differ in their structures, properties, modes of action, environmental behaviors, and effects on human health upon exposure. Humans can be exposed to disinfecting chemicals mainly through dermal absorption, inhalation, and ingestion. The total exposure and relative contribution of each exposure route vary considerably among the disinfectants. QACs have been linked to occupational illnesses such as asthma and an increased risk of chronic obstructive pulmonary disease (COPD), whereas excess use of bleach, hydrogen peroxide, or alcohol-based disinfectants can cause respiratory damage and has been linked to an increased risk of developing and controlling asthma. Recent studies showed that the presence of QACs in human blood has been associated with changes in health biomarkers such as an increase in inflammatory cytokines, decreased mitochondrial function, and disruption of cholesterol homeostasis in a dose-dependent manner. Therefore, repeated human exposure to disinfectants during the pandemic has raised questions on exposure-related long-term health risks and occupational safety. Furthermore, in lieu of a lack of adequate knowledge and public awareness, these chemicals have been frequently used on porous surfaces, including fabrics/textiles and consumer plastics and even for disinfecting cloth facemasks, on which disinfectant chemical residues may persist for longer duration, causing potential degradation of plastic materials, releasing additives, and shedding microplastics. In addition, the increased use of these disinfectant chemicals and the subsequent discharge into wastewater may cause adverse impacts on aquatic ecosystems, accumulation on vegetables, and contamination of the food chain via wastewater irrigation and sludge application. This article provides a well-rounded understanding of the most common disinfectants and reviews modes of action of those disinfectants, their interactions with aquatic and terrestrial environments, the exposure to humans, and potential impacts to human health and safety.

Quaternary Phosphonium Compounds: An Examination of Non-Nitrogenous Cationic Amphiphiles That Evade Disinfectant Resistance.

Quaternary ammonium compounds (QACs) serve as mainstays in the formulation of disinfectants and antiseptics. However, an over-reliance and misuse of our limited QAC arsenal has driven the development and spread of resistance to these compounds, as well as co-resistance to common antibiotics. Extensive use of these compounds throughout the COVID-19 pandemic thus raises concern for the accelerated proliferation of antimicrobial resistance and demands for next-generation antimicrobials with divergent architectures that may evade resistance. To this end, we endeavored to expand beyond canonical ammonium scaffolds and examine quaternary phosphonium compounds (QPCs). Accordingly, a synthetic and biological investigation into a library of novel QPCs unveiled biscationic QPCs to be effective antimicrobial scaffolds with improved broad-spectrum activities compared to commercial QACs. Notably, a subset of these compounds was found to be less effective against a known QAC-resistant strain of MRSA. Bioinformatic analysis revealed the unique presence of a family of small multiresistant transporter proteins, hypothesized to enable efflux-mediated resistance to QACs and QPCs. Further investigation of this resistance mechanism through efflux-pump inhibition and membrane depolarization assays illustrated the superior ability of P6P-10,10 to perturb the cell membrane and exert the observed broad-spectrum potency compared to its commercial counterparts. Collectively, this work highlights the promise of biscationic phosphonium compounds as next-generation disinfectant molecules with potent bioactivities, thereby laying the foundation for future studies into the synthesis and biological investigation of this nascent antimicrobial class.

Quaternary Ammonium Compounds: Bioaccumulation Potentials in Humans and Levels in Blood before and during the Covid-19 Pandemic.

Quaternary ammonium compounds (QACs) are commonly used in a variety of consumer, pharmaceutical, and medical products. In this study, bioaccumulation potentials of 18 QACs with alkyl chain lengths of C8-C18 were determined in the in vitro-in vivo extrapolation (IVIVE) model using the results of human hepatic metabolism and serum protein binding experiments. The slowest in vivo clearance rates were estimated for C12-QACs, suggesting that these compounds may preferentially build up in blood. The bioaccumulation of QACs was further confirmed by the analysis of human blood (sera) samples (n = 222). Fifteen out of the 18 targeted QACs were detected in blood with the ΣQAC concentrations reaching up to 68.6 ng/mL. The blood samples were collected during two distinct time periods: before the outbreak of the COVID-19 pandemic (2019; n = 111) and during the pandemic (2020, n = 111). The ΣQAC concentrations were significantly higher in samples collected during the pandemic (median 6.04 ng/mL) than in those collected before (median 3.41 ng/mL). This is the first comprehensive study on the bioaccumulation and biomonitoring of the three major QAC groups and our results provide valuable information for future epidemiological, toxicological, and risk assessment studies targeting these chemicals.