title: Characterization of potential impurities and degradation products in electronic cigarette formulations and aerosols.
abstract: E-cigarettes are gaining popularity in the U.S. as well as in other global markets. Currently, limited published analytical data characterizing e-cigarette formulations (e-liquids) and aerosols exist. While FDA has not published a harmful and potentially harmful constituent (HPHC) list for e-cigarettes, the HPHC list for currently regulated tobacco products may be useful to analytically characterize e-cigarette aerosols. For example, most e-cigarette formulations contain propylene glycol and glycerin, which may produce aldehydes when heated. In addition, nicotine-related chemicals have been previously reported as potential e-cigarette formulation impurities. This study determined e-liquid formulation impurities and potentially harmful chemicals in aerosols of select commercial MarkTen(®) e-cigarettes manufactured by NuMark LLC. The potential hazard of the identified formulation impurities and aerosol chemicals was also estimated. E-cigarettes were machine puffed (4-s duration, 55-mL volume, 30-s intervals) to battery exhaustion to maximize aerosol collection. Aerosols analyzed for carbonyls were collected in 20-puff increments to account for analyte instability. Tobacco specific nitrosamines were measured at levels observed in pharmaceutical grade nicotine. Nicotine-related impurities in the e-cigarette formulations were below the identification and qualification thresholds proposed in ICH Guideline Q3B(R2). Levels of potentially harmful chemicals detected in the aerosols were determined to be below published occupational exposure limits.
authors.affiliation: Altria Client Services LLC, 601 East Jackson Street, Richmond, VA 23219, United States. Electronic address: Jason.W.Flora@altria.com.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Flora
authors.affiliation: Altria Client Services LLC, 601 East Jackson Street, Richmond, VA 23219, United States.
authors.forename: Naren
authors.initials: N
authors.lastname: Meruva
authors.affiliation: Altria Client Services LLC, 601 East Jackson Street, Richmond, VA 23219, United States.
authors.forename: Chorng B
authors.initials: CB
authors.lastname: Huang
authors.affiliation: Altria Client Services LLC, 601 East Jackson Street, Richmond, VA 23219, United States.
authors.forename: Celeste T
authors.initials: CT
authors.lastname: Wilkinson
authors.affiliation: Altria Client Services LLC, 601 East Jackson Street, Richmond, VA 23219, United States.
authors.forename: Regina
authors.initials: R
authors.lastname: Ballentine
authors.affiliation: Altria Client Services LLC, 601 East Jackson Street, Richmond, VA 23219, United States.
authors.forename: Donna C
authors.initials: DC
authors.lastname: Smith
authors.affiliation: Altria Client Services LLC, 601 East Jackson Street, Richmond, VA 23219, United States.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Werley
authors.affiliation: Altria Client Services LLC, 601 East Jackson Street, Richmond, VA 23219, United States.
authors.forename: Willie J
authors.initials: WJ
authors.lastname: McKinney
mesh_terms: D000336:Aerosols; D000447:Aldehydes / Q000009:adverse effects / Q000032:analysis*; D000641:Ammonia / Q000032:analysis; D001151:Arsenic / Q000032:analysis; D002104:Cadmium / Q000032:analysis; D002626:Chemistry, Pharmaceutical; D004340:Drug Contamination; D004355:Drug Stability; D066300:Electronic Nicotine Delivery Systems / Q000009:adverse effects; D006801:Humans; D009538:Nicotine / Q000009:adverse effects / Q000032:analysis*; D018722:Nicotinic Agonists / Q000009:adverse effects / Q000032:analysis*; D009602:Nitrosamines / Q000009:adverse effects / Q000032:analysis*; D018570:Risk Assessment; D014835:Volatilization
chemical_list: D000336:Aerosols; D000447:Aldehydes; D018722:Nicotinic Agonists; D009602:Nitrosamines; D002104:Cadmium; D009538:Nicotine; D000641:Ammonia; D001151:Arsenic
keywords: Aerosol; E-cigarettes; E-vapor; Formulation; Harmful and potentially harmful constituents (HPHC)