AUC, area under the curve; CL, plasma clearance; CYP450, cytochrome P450; Cmax, peak plasma concentration; Cooling agent; FDA, Food and Drug Administration; FEMA GRAS; FEMA, Flavour and Extract Manufacturers Association of the United States; GMP, Good Manufacturing Practices; Genetic toxicological evaluation; HPBL, human peripheral blood lymphocytes; JV, jugular vein; LC/MS, liquid chromatography with mass spectrometry; MC, methylcellulose; NOAEL, no-observed-adverse-effect-level; NOEL, no-observed-effect-level; OECD, Organization for Economic Cooperation and Development; PCE, polychromatic erythrocytes; PK, pharmacokinetics; PV, portal vein; RCG, Relative Cell Growth; RMI, Relative Mitotic Index; S2227; Subchronic toxicological evaluation; TE, total erythrocytes; TK, toxicokinetics; TRPM8, transient receptor potential melastatin 8; Tmax, time to reach Cmax; Vss, volume of distribution at steady-state; mnPCE, micronucleated bone marrow polychromatic erythrocytes; t1/2, half-life