The in vitro toxicological assessment of oral nicotine products is an important component of the toxicological evaluation submitted in support of premarket tobacco product applications (PMTAs). The Nic Nac lozenges contain synthetic nicotine blended with xylitol, binders, and flavors. They do not contain cut, ground, powdered, or leaf tobacco and are made by blending all of the ingredients and compressing into a lozenge, using a tablet press. The use of these lozenge products is similar to a typical oral NRT lozenges such as Nicorette.
This toxicological assessment of nine flavored Nic Nac lozenge products with 6mg nicotine load was conducted using a battery of well-established in vitro regulatory assays, including the bacterial reverse mutation Ames assay (OECD TG 471); in vitro micronucleus assay (OECD TG 487); and the neutral red uptake cytotoxicity assay (OECD No. 129). For each product, extracts were prepared in dimethyl sulfoxide (DMSO) and evaluated within the established extract-stability window, as confirmed by nicotine analysis. Under the conditions of the assays and according to the predefined evaluation criteria, the Nic Nac lozenge products demonstrated no evidence of mutagenicity in the Ames assay, no evidence of genotoxicity in the in vitro micronucleus assay, and no evidence of cytotoxicity in the neutral red uptake assay.
These findings support the conclusion that the tested Nic Nac oral nicotine lozenge products do not raise an in vitro toxicological concern for mutagenicity, genotoxicity, or cytotoxicity under the experimental conditions evaluated.
