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A structure\u2010based grouping approach was used to select 38 flavor group representatives (FGR) on the basis of known and in silico\u2010predicted toxicological data. These FGRs were combined to create prototype e\u2010liquid formulations and tested against cigarette smoke (CS) in a 5\u2010week inhalation study.<\/jats:p><jats:p>Female A\/J mice were whole\u2010body exposed for 6\u2009h\/day, 5\u2009days\/week, for 5\u2009weeks to air, mainstream CS, or aerosols from (1) test formulations containing propylene glycol (PG), vegetable glycerol (VG), nicotine (N; 2% w\/w), and flavor (F) mixtures at low (4.6% w\/w), medium (9.3% w\/w), or high (18.6% w\/w) concentration or (2) base formulation (PG\/VG\/N). Male A\/J mice were exposed to air, PG\/VG\/N, or PG\/VG\/N\/F\u2010high under the same exposure regimen. There were no significant mortality or in\u2010life clinical findings in the treatment groups, with only transient weight loss during the early exposure adaptation period. 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