Photoinitiators and UV filters as triggers of oxidative stress damage: evidence from national monitoring to in vitro and in silico studies

• Paired dust–urine data show ubiquitous photoinitiator and UV filter pollution. • PI and UVF are significantly associated with multiple oxidative stress biomarkers. • Key drivers of oxidative stress include PI-184, BP, PI-651, BP-3, and UV-360. • In vitro assays confirm ROS and MDA elevation under mixed PI and UVF exposure. • Molecular docking and Western blot indicated disrupted antioxidant defense. This study investigated the mechanisms underlying oxidative stress damage associated with real-world exposure to Photoinitiators (PIs) and UV filters (UVFs). We analyzed 334 paired dust and urine samples collected across China and subsequently performed in vitro experiments, molecular docking, and Western blot analysis on the key identified pollutants. PIs and UVFs were ubiquitously detected in dust (medians: 559 and 636 ng/g) and urine (15.7 and 17.1 ng/mL). Dust concentrations were positively associated with regional economic development, whereas urinary levels were generally higher in females than in males. Multiple regression models revealed significant positive associations between urinary pollutant levels and seven oxidative stress biomarkers. PI-184, BP, PI-651, BP-3, and UV-360 were identified as major contributors. In HK-2 cells, these compounds induced dose-dependent cytotoxicity and significantly increased intracellular ROS and MDA levels. ROS staining further visualized enhanced intracellular oxidative stress after exposure. Molecular docking suggested that these compounds may interact with Keap1, Nrf2, and CAT. Western blot analysis further showed altered expression of Keap1, Nrf2, and CAT, supporting disruption of antioxidant defense pathways. These findings indicate that human exposure to PIs and UVFs may trigger oxidative stress damage and highlight their potential health risks.