Temporal Trends in Serum Benzophenone-Type Ultraviolet Filters and Longitudinal Associations of BP-3 with Lipids from 2008 to 2018: The Dongfeng-Tongji Cohort Study

Benzophenones (BPs) are widely used, and have been associated with metabolic disturbances in epidemiological and experimental studies, whereas longitudinal evidence on human exposure trends and metabolic effects remains limited. In this longitudinal study of five serum BPs among 216 retired workers from the Dongfeng-Tongji cohort across three survey waves from 2008 to 2018, we investigated temporal exposure trends and longitudinal repeated-measures associations between BP-3 concentrations and lipid profiles. BP-3 was the most frequently detected compound, and its concentration increased over time. Detection rates of BP-1, BP-2, BP-6, and BP-8 also increased. Each doubling of BP-3 was nominally associated with increases of 0.042 mmol/L (95% CI: 0.001, 0.082) in low-density lipoprotein cholesterol (LDL-C) and 0.049 mmol/L (95% CI: 0.003, 0.095) in nonhigh-density lipoprotein cholesterol (non-HDL-C), although neither remained statistically significant after multiple-testing correction. No association was observed for total cholesterol (TC) or triglycerides (TG). An adverse outcome pathway (AOP)-informed analysis integrating toxicogenomic, systems biology, and bioactivity evidence generated an exploratory mechanistic framework linking estrogen receptor- and peroxisome proliferator-activated receptor-related pathways to downstream lipid-regulatory processes. These findings indicate a changing BP exposure profile and suggestive associations between BP-3 exposure and cholesterol-related lipid measures, warranting confirmation in larger longitudinal and experimental studies.