Baviera_2025_Biochem.Pharmacol__117564

The present work investigates the in vitro hepatic metabolism of six commonly used sunscreen UV filters: oxybenzone, avobenzone, octocrylene, octinoxate, octisalate, and homosalate, using human liver microsomes. In vitro-in vivo extrapolation was performed to predict key metabolic parameters, including hepatic clearance (CL(H)) and hepatic extraction ratio (E(H)), providing valuable insights into the potential systemic persistence of these compounds after dermal or oral absorption. Additionally, reaction phenotyping was conducted for the first time to characterize the human liver enzymes involved in the metabolism of these sunscreen UV filters, with carboxylesterases (CES) playing a key role in the biotransformation of ester-containing compounds such as octocrylene and octinoxate. Furthermore, oxybenzone is predominantly metabolized by CYP2C19 and CYP1A2, while avobenzone is primarily metabolized by CYP2C19, CYP2C9, and CYP1A2. The results showed significant variability in metabolic stability and systemic clearance, with compounds like octocrylene exhibiting relatively higher half-lives, suggesting potential for bioaccumulation. The findings highlight the importance of understanding the kinetic profiles of sunscreen UV filters for more accurate risk assessments, particularly in the context of prolonged human exposure.