High-Throughput Identification of PPARγ-Active Chemicals in Riverine Drinking Water Sources: Discover a Novel DEHP Biodegradation Product

Abstract While exposure to PPAR active compounds can lead to various adverse health effects, studies on the environmental contaminants and their transformation products with PPAR activity remain limited. This study employed PPARγ protein affinity selection-mass spectrometry (AS-MS) to comprehensively identify and prioritize PPARγ-active contaminants in the Yangtze and Yellow Rivers, key drinking water sources in China. From wastewater treatment plant effluents, river, and source water samples, 61 PPARγ ligands were identified, including 18 antagonists not reported previously. Notably, a novel biodegradation product of di-2-ethylhexyl phthalate (DEHP), phthalic acid 1-(2-ethylhexyl) 2-(2-ethyl-5-carboxypentyl) ester (5CX-DEHP), was discovered and characterized as a potent PPARγ antagonist (IC50 = 8.5 μM). Semi-quantification revealed total concentrations of 61 chemicals ranging from 965.2 to 5748 ng/L in source waters, with priority agonistic chemicals such as 4-dodecylbenzenesulfonic acid and priority antagonistic chemicals such as 2-amino-6-methylmercaptopurine and 5CX-DEHP posing high ranking. This study comprehensively revealed the widespread occurrence of PPARγ agonistic and antagonistic chemicals in the water samples and identified a previously overlooked transformation product of DEHP as a relatively strong PPARγ antagonist.