The in vitro toxicological assessment of Modern Oral Nicotine Products (MONP) is an essential part of the US FDA’s premarket tobacco product application (PMTA) process. This assessment was conducted using a battery of well-established regulatory assays, including the Bacterial Reverse Mutation (Ames), in vitro Micronucleus (ivMN) and Neutral Red Uptake (NRU) regulatory assays to assess potential mutagenicity, genotoxicity, and cytotoxicity, respectively.   The Nic Nac Naturals (NNN) lozenges contain synthetic nicotine, xylitol, natural flavors, and binders and are made by mixing all of the ingredients and compressing the lozenge using a tablet press. The use of NNN lozenge products is similar to typical NRT lozenges. The lozenge is placed in the mouth under the lip until fully dissolved. There is no need to spit. The Nic Nac Naturals Blood Orange 6mg nicotine lozenge was extracted with dimethyl sulfoxide (DMSO) and used for toxicological assessment within the time frame of established extract stability by nicotine analysis. Under the experimental conditions and based on the established criteria for evaluation of various assays, no cytotoxicity, mutagenicity, nor genotoxicity was observed for the Nic Nac Naturals Blood Orange 6mg lozenge product.