Widespread formation of toxic nitrated bisphenols indoors by heterogeneous reactions with HONO

Abstract

With numerous structurally diverse indoor contaminants, indoor transformation chemistry has been largely unexplored. Here, by integrating protein affinity purification and nontargeted mass spectrometry analysis (PUCA), we identified a substantial class of previously unrecognized indoor transformation products formed through gas-surface reactions with nitrous acid (HONO). Through the PUCA, we identified a noncommercial compound, nitrated bisphenol A (BPA), from house dust extracts strongly binding to estrogen-related receptor γ. The compound was detected in 28 of 31 house dust samples with comparable concentrations (ND to 0.30 μg/g) to BPA. Via exposing gaseous HONO to surface-bound BPA, we demonstrated it likely forms via a heterogeneous indoor chemical transformation that is highly selective toward bisphenols with electron-rich aromatic rings. We used 15 N-nitrite for in situ labeling and found 110 nitration products formed from indoor contaminants with distinct aromatic moieties. This study demonstrates a previously unidentified class of chemical reactions involving indoor HONO, which should be incorporated into the risk evaluation of indoor contaminants, particularly bisphenols.

Nitration of Phenols by Reaction with Aqueous Nitrite: A Pathway for the Formation of Atmospheric Brown Carbon

“…Also, in laboratory aqueous phase studies, 3-methylcatechol was consumed when exposed to sodium nitrite under acidic conditions (pH 4.7) and the formation of 3-methylnitrocatechol was observed by liquid chromatography–UV absorption. , Interestingly, such aqueous nitration pathways are not limited to the production of nitroaromatics in the atmosphere. In a recent study of indoor dust, the same reaction is also observed heterogeneously with gas-phase HONO and bisphenols, producing more toxic nitrobisphenols . In the field of food chemistry, polyphenols, often found in grapes and tea, are considered good antioxidants for their nitrite scavenging ability …”

Building the Environmental Chemical-Protein Interaction Network (eCPIN): An Exposome-Wide Strategy for Bioactive Chemical Contaminant Identification

“…As mentioned above, we have already successfully applied the APNA method to multiple proteins including NRs, bacterial proteins, and transporter proteins. − Unexpectedly, we have found that a very small number of chemicals often contributed to the majority of bioactivity. For instance, hydrocarbon surfactants were recently identified as the predominant synthetic PPARγ ligands in sewage sludge and house dust, among >40,000 mass spectrometry features .…”

“…Similarly, we have identified 31 previously unknown polyfluoroalkyl ligands of the human liver fatty acid binding protein ( h L-FABP) from aqueous film-forming foam (AFFF) products and AFFF-contaminated surface waters (Figure b) through APNA . Another very intriguing example is the recent identification of nitro-bisphenol A (NO 2 –BPA) as a new estrogen related receptor γ (ERRγ) agonist in house dust (Figure c): with ERRγ as the “bait”, NO 2 –BPA was isolated from house dust extracts consisting of >20,000 mass spectrometry features . The chemical identity of the previously unknown ERRγ ligand, and its high binding affinity to ERRγ, was confirmed with a synthesized standard.…”

“…While a few chemicals exert toxicities by attacking nucleotides (e.g., polycyclic aromatic hydrocarbons and aromatic amines) or cell membranes (e.g., baseline toxicity), proteins mediate the toxicity of the majority of chemical contaminants . For instance, endocrine-disrupting chemicals (EDCs) exert their adverse effects primarily by interacting with NRs. , Considering this fundamental biochemistry principle, we highlighted a bioanalytical method “protein A ffinity P urification with N ontargeted A nalysis (APNA)” for the “ top-down ” screening of bioactive chemical contaminants at the exposome-wide level. − APNA uses a tagged protein of interest (e.g., a His-tagged NR) as a “bait” to directly isolate bioactive chemical contaminants from the extracts of environmental samples consisting of thousands of chemicals. Figure outlines the general steps involved in the APNA workflow.…”

“…Third, the identification of chemical contaminants remains highly challenging due to their distinct fragmentation pathways within mass spectrometers and the lack of comprehensive databases. Because of these challenges, no studies had successfully applied this concept for the screening of toxic contaminants until our development of the APNA method. − …”