title: In vitro human epidermal permeation of nicotine from electronic cigarette refill liquids and implications for dermal exposure assessment.
abstract: Nicotine plus flavorings in a propylene glycol (PG) vehicle are the components of electronic cigarette liquids (e-liquids), which are vaporized and inhaled by the user. Dermal exposure to nicotine and e-liquids may occur among workers in mixing and filling of e-cigarettes in the manufacturing process. Inadvertent skin contact among consumers is also a concern. In vitro nicotine permeation studies using heat-separated human epidermis were performed with surrogate and two commercial e-liquids, neat and aqueous nicotine donor formulations. Steady-state fluxes (Jss), and lag times (tlag) were measured for each formulation. In addition, transient (4 h) exposure and finite dose (1-10 μl/cm2) experiments were undertaken using one commercial e-liquid. Average Jss(μg/cm2/h) from formulations were: nicotine in PG (24 mg/ml): 3.97; commercial e-liquid containing menthol (25 mg/ml nicotine): 10.2; commercial e-liquid containing limonene (25 mg/ml nicotine): 23.7; neat nicotine: 175. E-liquid lag times ranged from 5 to 10 h. Absorbed fraction of nicotine from finite doses was ≈0.3 at 48 h. The data were applied to transient exposure and finite dose dermal exposure assessment models and to a simple pharmacokinetic model. Three illustrative exposure scenarios demonstrate use of the data to predict systemic uptake and plasma concentrations from dermal exposure. The data demonstrate the potential for significant nicotine absorption through skin contact with e-cigarette refill solutions and the neat nicotine used to mix them.
authors.affiliation: Health Effects Laboratory, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA.
authors.forename: H Frederick
authors.initials: HF
authors.lastname: Frasch
authors.affiliation: Health Effects Laboratory, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Barbero
mesh_terms: D066300:Electronic Nicotine Delivery Systems; D004781:Environmental Exposure / Q000032:analysis*; D004784:Environmental Monitoring / Q000379:methods; D005421:Flavoring Agents / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D009538:Nicotine / Q000032:analysis* / Q000378:metabolism*; D019946:Propylene Glycol / Q000032:analysis* / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption
chemical_list: D005421:Flavoring Agents; D019946:Propylene Glycol; D009538:Nicotine