Accurate establishment of in vitro-in vivo correlation (IVIVC) models for the bioavailability prediction of complex dermal products has been a challenge, leading to the use of multiple costly clinical studies for marketing approval. Although environmental conditions are highly controlled during in vitro permeation testing (IVPT), formulations such as lotions, gels, sprays and foams have historically generated variable absorptive profiles in vivo, making IVIVC mathematical modeling difficult. With no occlusive backing, dermal formulations undergo metamorphosis dependent upon environmental conditions, which are not typically precisely controlled during clinical testing. Since there are a wide range of formulations available on the market, sunscreens were selected as model products for translational evaluation. The goal of the present study was to examine multiple environmental and clinical factors in vitro that can alter absorption of the UV filter oxybenzone, and subsequently translate critical product testing conditions to a harmonized clinical protocol. Data from validated IVPT studies showed that temperature, dose and formulation were able to significantly alter the absorptive profile of oxybenzone. Therefore, a clinical study was designed utilizing four common dermal formulation types under un-occluded optimal dosing conditions with precise control of temperature and humidity during each procedure day. This human study data was then compared to prior sunscreen studies conducted by the US Food and Drug Administration (FDA), which did not include environmental controls during clinical assessment. The comparison showed that increased precision and harmonization between in vitro and in vivo methods for oxybenzone bioavailability assessment resulted in a decrease in variability associated with in vivo dermal product testing. Additionally, accurate IVIVC models for each formulation type tested were able to be generated. Models for in vivo exposure estimation of oxybenzone absorption from lotion, cream, solid stick and continuous spray sunscreen formulations were efficiently attained in a small number of healthy human volunteers with minimal dosage area required for predictable calculations of full body systemic exposure. This project lays the groundwork for effective pharmacokinetic (PK) safety and efficacy testing of other active pharmaceutical ingredients (API) absorbed from prescription and over-the-counter (OTC) complex dermal products.