FDA guidance is intended to assist in submitting PMTAs under section 910 of the FD&C Act, including reporting of HPHCs in tobacco and nicotine products and tobacco smoke under section 904(a)(3) of the FD&C Act.
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. Complete list of HPHC analytes (nicotine, carbonyls, TSNAs, metals and PAH) were analyzed for the highest nicotine strength (6mg) and partial HPHC analytes (nicotine and carbonyls) were tested at lower nicotine strength (3mg). These constituents originate from controlled trace impurities in raw materials and packaging and do not vary with nicotine content. Because the highest strength contains the same ingredients with the most conservative exposure scenario and demonstrated uniformly non-detect or extremely low levels, the 6mg product serves as an appropriate worst-case variant for these HPHCs.
HPHC results were evaluated both on a per-lozenge and on daily-consumption survey basis. Among tested HPHCs, acetaldehyde, crotonaldehyde, NNK, NNN, arsenic, cadmium and benzo[a]pyrene were not detected or were below quantitation limits for 6mg products. Only formaldehyde was detected in tested HPHC and it was present low levels in all products. Estimated daily formaldehyde exposure from the Nic Nac lozenges was calculated using the measured daily product-consumption rate and compared with established health-based oral exposure benchmarks, including the Permissible Daily Exposure approach under ICH M7(R2), the ATSDR Minimal Risk Level, and the ECHA Derived No-Effect Level, as applicable. Comparatively, the estimated daily formaldehyde exposure from the Nic Nac lozenges was several orders of magnitude below the applicable oral health-based exposure benchmarks.
Overall, the HPHC testing results indicate that the Nic Nac oral nicotine lozenges contain no detectable or quantifiable levels of the tested TSNAs, selected metals, benzo[a]pyrene, acetaldehyde, or crotonaldehyde, and only low levels of formaldehyde. Accordingly, formaldehyde at the measured concentrations is not expected to present a toxicological concern under the evaluated conditions of use and support the conclusion that HPHC-related exposures from these products are low.
