ABSTRACT BLACK BUFFALO Inc. (BB) has designed a line of novel alternative smokeless products that are based on a common non-tobacco food crop. The non-tobacco food crop leaf is cured and processed like tobacco. Tobacco derived nicotine is added to the processed leaf. The products are available in five flavors and two forms: loose (Long Cut) and fleece-portioned (Pouches). The filler material inside the Pouches products is the same as that used for the Long Cut products. BB’s products are designed to emulate the organoleptic, ritualistic, and pharmacokinetic aspects of traditional smokeless products but without the tobacco toxins. Standard smokeless tobacco HPHCs were analyzed on artificial saliva extracts of the products. Cytotoxicity (neutral red uptake test), mutagenicity (Ames test) and the genotoxicity (in vitro micronucleus test) were also performed on the saliva extracts. Market comparators Copenhagen Long Cut Wintergreen (Copenhagen) and General Snus Wintergreen Portion White (General Snus) products were evaluated for HPHCs under the same conditions. The BB products were well within GOTHIATEK® limits for each analyte. Copenhagen exceeded the GOTHIATEK® standard for B[a]P and NNN+NNK combined. B[a]P, crotonaldehyde, NNK, and NNN were either not detected or were below the limit of quantification for all eight of the BB products. B[a]P was detected in Copenhagen, and NNN was detected in both Copenhagen and General Snus comparator products. Versus the market comparators, the BB products had slightly higher levels of arsenic, acetaldehyde, and formaldehyde and similar levels of cadmium. None of the BB products demonstrated any cytotoxicity, mutagenicity or genotoxicity activity. The toxicity assays as well as the HPHC results demonstrate that the BLACK BUFFALO products are likely to have less risk than the market comparators. the HPHC results demonstrate that the Black Buffalo products are likely to have less risk than the market comparators.