A synthetic coolant (WS-23) in disposable electronic cigarettes impairs cytoskeletal function in EpiAirway microtissues exposed at the air liquid interface

Abstract

The design of popular disposable electronic cigarettes (ECs) was analyzed, and the concentrations of WS-23, a synthetic coolant, in EC fluids were determined for 22 devices from 4 different brands. All products contained WS-23 in concentrations that ranged from 1.0 to 40.1 mg/mL (mean = 21.4 ± 9.2 mg/mL). To determine the effects of WS-23 on human bronchial epithelium in isolation of other chemicals, we exposed EpiAirway 3-D microtissues to WS-23 at the air liquid interface (ALI) using a cloud chamber that generated aerosols without heating. Proteomics analysis of exposed tissues revealed that the cytoskeleton was a major target of WS-23. BEAS-2B cells were exposed to WS-23 in submerged culture to validate the main results from proteomics. F-actin, which was visualized with phalloidin, decreased concentration dependently in WS-23 treated BEAS-2B cells, and cells became immotile in concentrations above 1.5 mg/mL. Gap closure, which depends on both cell proliferation and migration, was inhibited by 0.45 mg/mL of WS-23. These data show that WS-23 is being added to popular EC fluids at concentrations that can impair processes dependent on the actin cytoskeleton and disturb homeostasis of the bronchial epithelium. The unregulated use of WS-23 in EC products may harm human health.

Ultrasonic Cigarettes: Chemicals and Cytotoxicity are Similar to Heated-Coil Pod-Style Electronic Cigarettes

“…Cells with depolymerized actin were often flat and spread, suggesting that their microtubules and/or intermediate filaments were still intact. Pure WS-23 caused depolymerization of actin filaments in an air–liquid interface exposed 3D bronchial epithelium and monolayers of BEAS-2B cells . and may have been responsible for the depolymerization of actin caused by SURGE.…”

“…WS-23 was originally developed by Wilkenson Sword for use in shaving cream 65,66 and is a relatively new additive in ecigarette products. 14,16,17 It caused depolymerization of actin filaments in BEAS-2B cells exposed at the air−liquid interface in a cloud chamber, leading to impaired motility and a collapse of cell architecture 67 and may have been a factor in depolymerizing actin in cells treated with the SURGE aerosols.…”

“…Pure WS-23 caused depolymerization of actin filaments in an air−liquid interface exposed 3D bronchial epithelium and monolayers of BEAS-2B cells. 67 and may have been responsible for the depolymerization of actin caused by SURGE. Similar to prior data with 16 PUFF products, 14 the concentrations of WS-23 in SURGE unvaped fluid were high enough to produce MOEs below the threshold of 100, indicating a potential health risk.…”

“…WS-23 transferred to the aerosol with high efficiency (62 to 92%), and like nicotine, its concentrations in both fluids and aerosols were highly correlated with toxicity in the MTT assay. WS-23 was originally developed by Wilkenson Sword for use in shaving cream , and is a relatively new additive in e-cigarette products. ,, It caused depolymerization of actin filaments in BEAS-2B cells exposed at the air–liquid interface in a cloud chamber, leading to impaired motility and a collapse of cell architecture and may have been a factor in depolymerizing actin in cells treated with the SURGE aerosols.…”

Challenges in current inhalable tobacco toxicity assessment models: A narrative review

“…Studies have shown that the aerosol from non-combustible products are associated with altered immune responses, inflammation, and oxidative stress responses similar to combustible products 9 - 22 . Given the risk of health effects on the respiratory, cardiovascular, and systemic effects, many studies have used cell lines, primary cell cultures, and animal models representing target organ toxicity.…”