This study is a first-in-human study of a topical dermal lotion formulation of RTA 408, a novel small molecule which suppresses oxidative stress and inflammation. In this study, the safety, local pharmacodynamics (PD), and systemic pharmacokinetics (PK) of RTA 408 will be evaluated following topical application of RTA 408 Lotion to healthy volunteers. This study will be conducted in three parts. In Part A of the study, healthy volunteers will have RTA 408 Lotion Vehicle and RTA 408 Lotion (0.5%, 1%, and 3%) applied to a small skin surface area (four individual 4-cm2 sites; 16 cm2 total area) twice daily for 14 days to assess the local skin tolerability, local PD, and systemic PK of these treatments. Part B will be conducted after completion of Part A and will assess the safety, tolerability, local PD, and systemic PK of RTA 408 Lotion applied topically twice daily for 14 days to a larger skin surface area (~100 cm2). Part C will be conducted after completion of Part B and will assess the safety, tolerability, local PD, and systemic PK of RTA 408 Lotion applied topically twice daily for 28 days to a larger skin surface area (~500 cm2). The maximum tolerated drug concentration in Part A will be used in Part B and Part C.