A significant scientific, regulatory, and economic need exists to distinguish tobacco-derived nicotine (TDN) from synthetic nicotine (SynNic) to assess its use in commercial products. Products containing TDN are regulated by FDA; however those with SynNic are currently exempt from regulatory authority which has resulted in a regulatory loophole for SynNic commercialization. The regulatory gap has resulted in significant numbers of new products that are largely manufactured with uncertainty of their safety and efficacy. There are obvious consumer implications associated with the use of SynNic products since they are not subject to any scientific, manufacturing or marketing standards, in contrast to products which are subject to a PMTA.

Moreover, SynNic frequently contains a substantial proportion of the poorly characterized (R)-nicotine enantiomer. TDN is typically comprised of the ~99.3% (S)-nicotine enantiomer, while SynNic from traditional syntheses is racemic (i.e., 50/50 (R)-nicotine and (S)-nicotine enantiomers). SynNic can be enantiomerically purified to obtain >99% S nicotine, making it indistinguishable from TDN using existing chromatographic methods. High costs and technical challenges of SynNic purification have resulted in low quality and mislabeled products and use of SynNic is increasing despite the lack of scientific confidence in utilizing the racemic mixture.

Currently there is scant toxicological or physiological data for the (R) enantiomer and no published studies which differentiate between TDN and SynNic in commercial SynNic products. The toxicological and pharmacological effects associated with high amounts of (R) nicotine are unpredictable and possibly unsafe, due to its different binding and activity versus (S) nicotine.

Here we discuss the impacts of SynNic on industry, including the SynNic loophole, potential regulatory paths, potential product standards and scientific challenges associated with the use of SynNic.