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In vitro dermal permeation of nicotine from surrogate e-cigarette liquids.

Frasch H; Barbero AM
Toxicologist 2014 Mar; 138(1):571
Rationale and Scope: Nicotine (NIC) in propylene glycol (PG) plus flavorings form the main delivery components of electronic cigarettes (e-cigarettes). Some flavoring constituents, e.g. limonene, are known to enhance dermal penetration. Workers mix these liquids and fill e-cigarette cartridges in the manufacturing process, creating the potential for dermal exposure. No information currently exists on the dermal absorption of nicotine from propylene glycol vehicle. Therefore, in vitro human epidermal permeation of NIC from 24 mg/mL ("high strength") solutions in PG and from neat NIC were measured. Preliminary studies from 24 mg/mL NIC in PG with the addition of 5% (w/w) limonene were also undertaken. Procedures: Both steady-state fluxes (Jss, ug/cm2/h) and lag times (t, h) were determined from infinite dose exposures of 8 h (neat NIC, 9 samples from 3 donors) or 26 h (NIC + PG, 9 samples from 3 donors; NIC + PG + limonene, 3 samples from 1 donor) using static diffusion cells. NIC was quantified by HPLC. Results: Jss from NIC + PG was 4.0 - 2.3 (mean + SD). Addition of 5% limonene substantially enhanced flux to 84 - 23. Jss from neat NIC was 175 + 57. Measured t's were: NIC + PG: 10.1 + 3.3; NIC + PG + limonene: 5.2 + 2.6; neat NIC: 1.9 + 0.7. Application of a risk assessment paradigm predicts, for an 8 h exposure to the volar surface of fingertips (73 cm2) followed by washing, the following average total NIC uptakes (mg): NIC + PG: 7.3; NIC + PG + limonene: 110; neat NIC: 152. Because the typical NIC intake from a smoked cigarette 1 mg, these numbers may also be thought of as "cigarette equivalents" consumed over an 8 h work shift. Conclusions: These data suggest the potential for substantial systemic nicotine uptake from occupational exposures in the manufacture of e-cigarettes. The addition of flavorings may significantly enhance systemic uptake.
Toxicology; Exposure-levels; Humans; Men; Women; Toxins; Risk-factors; Propylenes; In-vitro-study; Skin-absorption; Skin-exposure; Skin; Workers; Chemical-composition; Chemical-properties; Chemical-reactions
54-11-5; 57-55-6; 138-86-3
Publication Date
Document Type
Fiscal Year
Identifying No.
Issue of Publication
NIOSH Division
Priority Area
Manufacturing; Services
Source Name
The Toxicologist. Society of Toxicology 53rd Annual Meeting and ToxExpo, March 23-27, 2014, Phonex, Arizona
Page last reviewed: April 8, 2022
Content source: National Institute for Occupational Safety and Health Education and Information Division