Simulated Epidermal Formation of Tobacco-Specific Nitrosamines (TSNAs) from the Nitrosation of Nicotine with Atmospheric HONO
XIAOCHEN TANG, Peyton Jacob III, Christopher Havel, Marion Russell, Neal Benowitz, Lara Gundel, Hugo Destaillats,
Lawrence Berkeley National Laboratory Abstract Number: 75
Working Group: Indoor Aerosols
AbstractTobacco-specific nitrosamines (TSNAs) are emitted during smoking, and can be produced in the indoor environment after smoking has ended. Among them, N’-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are human carcinogens with no significant risk levels (NSRLs) of 500 and 14 ng day
-1, respectively. 4-(methylnitrosamino)-4-(3-pyridyl) butanal (NNA), shows genotoxic and mutagenic activity in vitro. Because of the presence of nicotine on thirdhand smoke (THS)-laden indoor surfaces and human skin, and the emissions of HONO from combustion sources of indoor and outdoor origin, TSNAs are expected to be formed continuously in indoor environments impacted by smoking.
We investigated the effects of skin constituents on the reaction of adsorbed nicotine with HONO on different model substrates. Individual specimens containing a known surface concentration of nicotine were placed inside a flow chamber and exposed to HONO-enriched air (500 ppb, 50% RH) for 1 hour. The fraction of consumed HONO was determined by ion chromatography. Extracts of the exposed specimens were analyzed by LC-MS/MS to quantify TSNAs, and by GC/MS for the remaining nicotine. Higher TSNA concentrations (0.3 – 3.7 ng cm
-2) were formed on cellulose and cotton substrates coated with human skin oils and sweat, with respect to clean substrates. In all extracts, NNA levels were highest, while NNK was present at higher concentration than NNN. These results were combined with reported air, dust and surface concentrations to assess potential NNK daily intakes. Three different dermal uptake pathways (by direct contact, air-to-skin deposition and epidermal nitrosation of nicotine) were predicted to exceed the NSRL in realistic scenarios, contributing significantly to total NNK intake at comparable levels as inhalation. Results illustrated that exposure to NNK via multiple pathways could increase cancer risk for adult non-smokers exposed to THS indoors.