Protein-Affinity-Guided Identification of Bioaccumulative Silanol Quaternary Ammonium Compounds in Indoor Environments and Human Serum.

Quaternary ammonium compounds (QACs) have raised concerns due to their widespread use in disinfectants and unknown bioaccumulation behavior. However, conventional bioaccumulation assessments are costly, time-consuming, and low-throughput, limiting their utility for screening the growing array of emerging QACs. In this study, we developed a protein affinity ultrafiltration mass spectrometry (PA-UF-MS) strategy using human serum albumin (HSA) as a molecular bait to selectively isolate bioaccumulative QACs from disinfectants. We identified 12 traditional and emerging QACs, including several silanol alkyltrimethylammonium compounds (silanol-ATMACs), with strong HSA binding affinities [fold changes (FCs): 10.1-60.0]. Five silanol-ATMACs (C10-C18) were further structurally elucidated by MS/MS characterization and confirmed via a hydrolysis-based transformation experiment. In silico toxicokinetic modeling and in vivo rat experiments revealed longer elimination half-lives for silanol-ATMACs compared to ATMACs, indicating their bioaccumulation potential. These silanol-ATMACs were mainly detected in medical disinfectants with a median total concentration (∑silanol-ATMAC) of 779 mg/L. While detected at modest levels in indoor dust (median: 8.04 ng/g), silanol-ATMACs exhibited elevated concentrations in human serum, comparable to those of 18 traditional QACs (medians: 10.6 and 13.9 ng/mL, respectively). Our findings demonstrate the application of PA-UF-MS for prioritizing emerging bioaccumulative contaminants and highlight the need for further toxicological evaluation and human exposure assessment of silanol-ATMACs.