E-cigarettes utilize a wide range of flavoring chemicals with respiratory health effects that are not well understood. In this study, we used pulmonary-associated cell lines to assess the in vitro cytotoxic effects of 30 flavoring chemicals. Human bronchial epithelial cells (BEAS-2B) and both naïve and activated macrophages (THP-1) were treated with 10, 100, and 1000 µM of flavoring chemicals and analyzed for changes in viability, cell membrane damage, reactive oxygen species (ROS) production, and inflammatory cytokine release. Viability was unaffected for all chemicals at the 10 and 100 µM concentrations. At 1000 µM, the greatest reductions in viability were seen with decanal, hexanal, nonanal, cinnamaldehyde, eugenol, vanillin, alpha-pinene, and limonene. High amounts of ROS were elicited by vanillin, ethyl maltol, and the diketones (2,3-pentanedione, 2,3-heptanedione, and 2,3-hexanedione) from both cell lines. Naïve THP-1 cells produced significantly elevated levels of IL-1β, IL-8, and TNF-α when exposed to ethyl maltol and hexanal. Activated THP-1 cells released increased IL-1β and TNF-α when exposed to ethyl maltol, but many flavoring chemicals had an apparent suppressive effect on inflammatory cytokines released by activated macrophages, some with varying degrees of accompanying cytotoxicity. The diketones, L-carvone, and linalool suppressed cytokine release in the absence of cytotoxicity. These findings provide insight into lung cell cytotoxicity and inflammatory cytokine release in response to flavorings commonly used in e-cigarettes.

E-cigarettes are battery-operated devices that heat a liquid mixture to make an aerosol that is inhaled, or vaped, by the user. Vape shops are retail environments for customer demand of diverse e-liquid flavors and hardware options, which create unique worker exposure concerns. To characterize exposures to vape shop workers, especially to flavoring chemicals associated with known respiratory toxicity, this study recruited vape shops from the San Francisco Bay Area. In six shops, air concentrations were measured for volatile organic compounds, formaldehyde, flavoring chemicals, and nicotine in personal and/or area samples; analyzed components of e-liquids vaped during field visits; and assessed metals on surface wipe samples. Interviews and observations were conducted over the course of a workday in the same six shops and performed interviews only in an additional six where sampling was not conducted. Detections of the alpha-diketone butter flavoring chemicals diacetyl and/or 2,3-pentanedione were common: in the headspace of purchased e-liquids (18 of 26 samples), in personal air samples (five of 16), and in area air samples (two of six shops). Two exceedances of recommended exposure limits for 2,3-pentanedione (a short-term exposure limit and an eight-hour time weighted average) were measured in personal air samples. Other compounds detected in area and personal air samples included substitutes for diacetyl and 2,3-pentanedione (acetoin and 2,3-hexanedione) and compounds that may be contaminants or impurities. Furthermore, a large variety (82) of other flavoring chemicals were detected in area air samples. None of the 12 shops interviewed had a health and safety program. Six shops reported no use of any personal protective equipment (PPE) (e.g., gloves, chemical resistant aprons, eye protection) and the others stated occasional use; however, no PPE use was observed during any field investigation day. Recommendations were provided to shops that included making improvements to ventilation, hygiene, use of personal protective equipment, and, if possible, avoidance of products containing the alpha-diketone flavoring chemicals. Future research is needed to evaluate the long-term health risks among workers in the vape shop retail industry and for e-cigarette use generally. Specific areas include further characterizing e-liquid constituents and emissions, evaluating ingredient health risks, evaluating the contributions of different routes of exposure (dermal, inhalation, and ingestion) and determining effective exposure mitigation measures.

Upholstered furniture has been a major source of flame retardant (FR) exposures in the United States. However, the California update to furniture flammability standards has allowed compliance without relying on chemical additives. We investigated whether FR biomarkers would decrease in participants who replaced furniture foam or upholstered furniture with items manufactured after the policy change. Building off previous work demonstrating decreased dust FR concentrations after furniture replacement, we collected urine and blood from 25 participants prior to furniture replacement and approximately one year after and from a comparison group (n = 28) over a similar time frame. Serum was analyzed for 19 polybrominated diphenyl ethers (PBDEs) and urine for 3 metabolites of organophosphate FRs (OPFRs). For BDE-47, BDE-99, and BDE-100, time to decline by half was 1.9-3.9 times longer in the comparison group than the replacement group (equivalent to 1.4 years (median) in the replacement group versus 2.6-5.2 years in the comparison group). For BDE-153, times to decline by half were not significantly different. For OPFR metabolites, which are excreted within days after exposure, concentration changes were much more variable. Nonsignificant greater decreases were seen for bis(1,3-dichloroisopropyl) phosphate in the replacement group and for diphenyl phosphate in the comparison group, whereas concentrations remained level or increased for bis(2-chloroethyl) phosphate. Moderate positive correlations were observed for baseline PBDE concentrations with baseline dust concentrations (ρ = 0.58-0.60); OPFRs were less correlated. Magnitudes of change were mostly positively correlated between dust and biomarker concentrations but not significant. Overall, results indicate that updated flammability standards can reduce FR exposures.