Exposure Profile and Combined Effects of Human PPARγ Agonists in Residential Indoor Dust from China

The activation of peroxisome proliferator-activated receptor γ (PPARγ) represents a primary biological mechanism underlying the adverse effects of environmental adipogens. However, a holistic understanding of the composition profiles of PPARγ agonists in complex environmental matrices remains elusive. In this study, an integrated workflow of knowledge-based suspect screening combined with in vitro bioassays enabled the comprehensive identification and prioritization of the main contributing components in indoor dust from Chinese residential areas. All mixed dust extracts activated PPARγ within the exposure concentration range (7.8 × 10^-2-10 mg dust/mL assay medium). A total of 123 putative agonists covering 35 structural categories were found, among which 30 chemicals were verified as specific PPARγ agonists through reference standards and in vitro assays. These agonists could explain up to 84% of the effect in the mixed dust extracts, with phthalates (31% ± 19%), fatty acids (12% ± 9%), quaternary ammonium compounds (2% ± 1%), and hydrocarbon surfactants (2% ± 1%) being the major contributors. The concentration addition model was validated to effectively characterize the combined effects of these PPARγ agonists via the artificial mixture experiments. These results suggest that the workflow holds promise for the overall perception of bioactive components related to toxicological end points in environmental samples.