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Development of an In Vitro Porcine Buccal Model to Determine Permeability of Tobacco HPHCs

Principal Investigator: Jeffrey Yourick, Juan Crespo-Barreto and Dana Lauterstein

Funding Mechanism: Performance Agreement

ID number: PA-DNCS-001-16

Award Date: 1/12/2017

Institution: Center for Food Safety and Applied Nutrition (CFSAN)

Measuring the absorption of harmful and potentially harmful constituents (HPHCs) in tobacco products through mouth exposure is important for understanding the toxic effects of these constituents.  The goal of this study is to develop a measure of HPHC absorption (a “permeability constant”) that will allow investigators to predict how a given dose of a constituent absorbed through the mouth contributes to the relative risk of that constituent.  In Phase 1 of the study, investigators will conduct a literature search on the physical and chemical properties of each constituent as well as their absorption through other membranes (i.e., skin, mucus membranes).  In Phase 2, investigators will use an in vitro buccal (mouth) membrane absorption pig model to determine the permeability constants for five HPHCs found in smokeless tobacco: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), nicotine, benzo[a]pyrene, crotonaldehyde, and arsenic.  In Phase 3, investigators will use the model to evaluate HPHC properties in three to five different types of three smokeless tobacco products (moist snuff [including a reference product], dissolvables, and snus), and will measure the absorption percentage of each constituent.  These results will be compared to the results generated in Phase 2.  Study findings will provide new information about buccal absorption of HPHCs.

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