Comparison of product safety data sheet ingredient lists with skin irritants and sensitizers present in a convenience sample of light-curing resins used in additive manufacturing.

Material jetting and vat photopolymerization additive manufacturing (AM) processes use liquid resins to build objects. These resins can contain skin irritants and/or sensitizers but product safety data sheets (SDSs) might not declare all ingredients. We characterized elemental and organic skin irritants and sensitizers present in 39 commercial products; evaluated the influence of resin manufacturer, system, color, and AM process type on the presence of irritants and sensitizers; and compared product SDSs to results. Among all products, analyses identified 23 irritant elements, 54 irritant organic substances, 22 sensitizing elements, and 23 sensitizing organic substances; SDSs listed 3, 9, 4, and 6 of these ingredients, respectively. Per product, the number and total mass (an indicator of potential dermal loading) of ingredients varied: five to 17 irritant elements (8.32-4756.65 mg/kg), one to 17 irritant organics (3273 to 356,000 mg/kg), four to 17 sensitizing elements (8.27-4755.63 mg/kg), and one to seven sensitizing organics (15-382,170 mg/kg). Median numbers and concentrations of irritants and sensitizers were significantly influenced by resin system and AM process type. The presence of undeclared irritants and sensitizers in these resins supports the need for more complete information on product SDSs for comprehensive dermal risk assessments.

Influence of E-Liquid Humectants, Nicotine, and Flavorings on Aerosol Particle Size Distribution and Implications for Modeling Respiratory Deposition.

Electronic cigarette, or vaping, products are used to heat an e-liquid to form an aerosol (liquid droplets suspended in gas) that the user inhales; a portion of this aerosol deposits in their respiratory tract and the remainder is exhaled, thereby potentially creating opportunity for secondhand exposure to bystanders (e.g., in homes, automobiles, and workplaces). Particle size, a critical factor in respiratory deposition (and therefore potential for secondhand exposure), could be influenced by e-liquid composition. Hence, the purposes of this study were to (1) test the influence of laboratory-prepared e-liquid composition [ratio of propylene glycol (PG) to vegetable glycerin (VG) humectants, nicotine, and flavorings] on particle size distribution and (2) model respiratory dosimetry. All e-liquids were aerosolized using a second-generation reference e-cigarette. We measured particle size distribution based on mass using a low-flow cascade impactor (LFCI) and size distribution based on number using real-time mobility sizers. Mass median aerodynamic diameters (MMADs) of aerosol from e-liquids that contained only humectants were significantly larger compared with e-liquids that contained flavorings or nicotine (p = 0.005). Humectant ratio significantly influenced MMADs; all aerosols from e-liquids prepared with 70:30 PG:VG were significantly larger compared with e-liquids prepared with 30:70 PG:VG (p = 0.017). In contrast to the LFCI approach, the high dilution and sampling flow rate of a fast mobility particle sizer strongly influenced particle size measurements (i.e., all calculated MMAD values were < 75 nm). Dosimetry modeling using LFCI data indicated that a portion of inhaled particles will deposit throughout the respiratory tract, though statistical differences in aerosol MMADs among e-liquid formulations did not translate into large differences in deposition estimates. A portion of inhaled aerosol will be exhaled and could be a source for secondhand exposure. Use of laboratory-prepared e-liquids and a reference e-cigarette to standardize aerosol generation and a LFCI to measure particle size distribution without dilution represents an improved method to characterize physical properties of volatile aerosol particles and permitted determination of MMAD values more representative of e-cigarette aerosol in situ, which in turn, can help to improve dose modeling for users and bystanders.

Potential for Exposure to Particles and Gases throughout Vat Photopolymerization Additive Manufacturing Processes.

Vat photopolymerization (VP), a type of additive manufacturing process that cures resin to build objects, can emit potentially hazardous particles and gases. We evaluated two VP technologies, stereolithography (SLA) and digital light processing (DLP), in three separate environmental chambers to understand task-based impacts on indoor air quality. Airborne particles, total volatile organic compounds (TVOCs), and/or specific volatile organic compounds (VOCs) were monitored during each task to evaluate their exposure potential. Regardless of duration, all tasks released particles and organic gases, though concentrations varied between SLA and DLP processes and among tasks. Maximum particle concentrations reached 1200 #/cm3 and some aerosols contained potentially hazardous elements such as barium, chromium, and manganese. TVOC concentrations were highest for the isopropyl alcohol (IPA) rinsing, soaking, and drying post-processing tasks (up to 36.8 mg/m3), lowest for the resin pouring pre-printing, printing, and resin recovery post-printing tasks (up to 0.1 mg/m3), and intermediate for the curing post-processing task (up to 3 mg/m3). Individual VOCs included, among others, the potential occupational carcinogen acetaldehyde and the immune sensitizer 2-hydroxypropyl methacrylate (pouring, printing, recovery, and curing tasks). Careful consideration of all tasks is important for the development of strategies to minimize indoor air pollution and exposure potential from VP processes.

Toxicology of flavoring- and cannabis-containing e-liquids used in electronic delivery systems.

Electronic cigarettes (e-cigarettes) were introduced in the United States in 2007 and by 2014 they were the most popular tobacco product amongst youth and had overtaken use of regular tobacco cigarettes. E-cigarettes are used to aerosolize a liquid (e-liquid) that the user inhales. Flavorings in e-liquids is a primary reason for youth to initiate use of e-cigarettes. Evidence is growing in the scientific literature that inhalation of some flavorings is not without risk of harm. In this review, 67 original articles (primarily cellular in vitro) on the toxicity of flavored e-liquids were identified in the PubMed and Scopus databases and evaluated critically. At least 65 individual flavoring ingredients in e-liquids or aerosols from e-cigarettes induced toxicity in the respiratory tract, cardiovascular and circulatory systems, skeletal system, and skin. Cinnamaldehyde was most frequently reported to be cytotoxic, followed by vanillin, menthol, ethyl maltol, ethyl vanillin, benzaldehyde and linalool. Additionally, modern e-cigarettes can be modified to aerosolize cannabis as dried plant material or a concentrated extract. The U.S. experienced an outbreak of lung injuries, termed e-cigarette, or vaping, product use-associated lung injury (EVALI) that began in 2019; among 2,022 hospitalized patients who had data on substance use (as of January 14, 2020), 82% reported using a delta-9-tetrahydrocannabinol (main psychoactive component in cannabis) containing e-cigarette, or vaping, product. Our literature search identified 33 articles related to EVALI. Vitamin E acetate, a diluent and thickening agent in cannabis-based products, was strongly linked to the EVALI outbreak in epidemiologic and laboratory studies; however, e-liquid chemistry is highly complex, and more than one mechanism of lung injury, ingredient, or thermal breakdown product may be responsible for toxicity. More research is needed, particularly with regard to e-cigarettes (generation, power settings, etc.), e-liquids (composition, bulk or vaped form), modeled systems (cell type, culture type, and dosimetry metrics), biological monitoring, secondhand exposures and contact with residues that contain nicotine and flavorings, and causative agents and mechanisms of EVALI toxicity.