title: Distribution, quantification and toxicity of cinnamaldehyde in electronic cigarette refill fluids and aerosols.
abstract: The aim of this study was to evaluate the distribution, concentration and toxicity of cinnamaldehyde in electronic cigarette (e-cigarette) refill fluids and aerosols.
  
  
  
  The distribution and concentration of cinnamaldehyde were determined in 39 e-cigarette refill fluids plus 6 duplicates using gas chromatography and mass spectrometry (GC/MS). A cinnamaldehyde toxicity profile was established for embryonic and adult cells using a live cell imaging assay, immunocytochemistry, the comet assay and a recovery assay.
  
  
  
  Twenty of the 39 refill fluids contained cinnamaldehyde at concentrations that are cytotoxic to human embryonic and lung cells in the MTT assay. Cinnamon Ceylon aerosol produced in a cartomizer-style e-cigarette was cytotoxic. Cinnamon Ceylon aerosols and refill fluid aerosols (80% propylene glycol or cinnamaldehyde/propylene glycol) made using a tank/boxmod e-cigarette were more cytotoxic at 5 V than 3 V. Using GC/MS, aerosols produced at 5 V contained 10 additional peaks not present in aerosol generated at 3 V. One of these, 2,3-butandione (diacetyl), was confirmed with an authentic standard. Cinnamaldehyde depolymerised microtubules in human pulmonary fibroblasts. At concentrations that produced no effect in the MTT assay, cinnamaldehyde decreased growth, attachment and spreading; altered cell morphology and motility; increased DNA strand breaks; and increased cell death. At the MTT IC50concentration, lung cells were unable to recover from cinnamaldehyde after 2 hours of treatment, whereas embryonic cells recovered after 8 hours.
  
  
  
  Cinnamaldehyde-containing refill fluids and aerosols are cytotoxic, genotoxic and low concentrations adversely affect cell processes and survival. These data indicate that cinnamaldehyde in e-cigarette refill fluids/aerosols may impair homeostasis in the respiratory system.
authors.affiliation: Cell Molecular and Developmental Biology Graduate Program, University of California, Riverside, California, USA.|UCR Stem Cell Center, University of California, Riverside, California, USA.|Department of Cell Biology and Neuroscience, University of California, Riverside, California, USA.
authors.forename: Rachel Z
authors.initials: RZ
authors.lastname: Behar
authors.affiliation: Department of Civil and Environmental Engineering, Portland State University, Portland, Oregon, USA.
authors.forename: Wentai
authors.initials: W
authors.lastname: Luo
authors.affiliation: UCR Stem Cell Center, University of California, Riverside, California, USA.|Department of Cell Biology and Neuroscience, University of California, Riverside, California, USA.
authors.forename: Sabrina C
authors.initials: SC
authors.lastname: Lin
authors.affiliation: UCR Stem Cell Center, University of California, Riverside, California, USA.|Department of Cell Biology and Neuroscience, University of California, Riverside, California, USA.
authors.forename: Yuhuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: UCR Stem Cell Center, University of California, Riverside, California, USA.|Department of Cell Biology and Neuroscience, University of California, Riverside, California, USA.
authors.forename: Jackelyn
authors.initials: J
authors.lastname: Valle
authors.affiliation: Department of Civil and Environmental Engineering, Portland State University, Portland, Oregon, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Pankow
authors.affiliation: UCR Stem Cell Center, University of California, Riverside, California, USA.|Department of Cell Biology and Neuroscience, University of California, Riverside, California, USA.
authors.forename: Prue
authors.initials: P
authors.lastname: Talbot
mesh_terms: D000171:Acrolein / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D000328:Adult; D000336:Aerosols; D002478:Cells, Cultured; D020552:Comet Assay; D053960:DNA Breaks / Q000187:drug effects; D066300:Electronic Nicotine Delivery Systems; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007150:Immunohistochemistry; D020128:Inhibitory Concentration 50; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000336:Aerosols; D000171:Acrolein; C012843:cinnamaldehyde
keywords: Electronic nicotine delivery devices; Global health; Toxicology