Toxicokinetics, Percutaneous Absorption and Tissue Distribution of Benzophenone-3, an UV Filtering Agent, in Rats

Abstract

The aim of this study was to evaluate in vitro skin permeation and deposition, in vivo toxicokinetics, percutaneous absorption and tissue distribution of benzophenone-3 (BP-3) in rats. Four transdermal formulations containing BP-3 were prepared and evaluated for in vitro skin permeation and deposition of BP-3 using Franz diffusion cells. A gel formulation was used in subsequent in vivo percutaneous absorption due to its high in vitro skin permeation and deposition. Compared to intravenous (i.v.) injection, the prolonged terminal t(1/2) (3.1 +/- 1.6 h for i.v. injection and 18.3 +/- 5.8 h for topical application) was observed indicating occurrence of flip-flop kinetics after topical application. The bioavailability of BP-3 after topical application was 6.9 +/- 1.8%. The tissue-to-plasma partition coefficient (kp) for testis, considered a toxic target for BP-3, was less than 1. Overall, findings of this study may be useful for risk assessment of BP-3.