Analysis of potential human accumulation differences and mechanisms of environmental new flame retardants: Based on in vitro experiments and theoretical calculations.

Hundreds of new flame retardants (NFRs) are widely used, causing environmental pollution and threating human health. In this study, based on the interaction of NFRs and human serum albumin (HSA), we assessed the differences in potential human accumulation of 8 NFRs including 1,2-Dibromo-4-(1,2-dibromoethyl)cyclohexane (TBECH), tetrabromobisphenol A bis(dibromopropyl ether) (TBBPA-DBPE), 2,4,6-tribromophenol (TBP), pentabromophenol (PBP), tri-n-butyl phosphate (TnBP), triphenyl phosphate (TPP), Tri(2-chloroethyl) phosphate (TCEP), and Tri(1,3-dichloro-2-propyl) phosphate (TDCP). All NFRs could bind to HSA and cause slight damage to its structure, suggesting their potential human accumulation ability. Notably, the binding pocket of site 1 was larger than that of site 2, so TBBPA-DBPE with a larger molecular volume exhibited a preference for binding to site 1 and other NFRs with smaller volume bound to site 2. Binding constant (K) analysis revealed that TBP and PBP had strongest potential human accumulation ability (K: 6.35 × 10-7.84 × 10 L/mol), followed by TnBP, TPP, TCEP, and TDCP (K: 3.50 × 10-7.80 × 10 L/mol), while TBBPA-DBPE and TBECH presented the lowest ability (K: 5.84 × 10-8.05 × 10 L/mol). Theoretical calculations demonstrated that the magnitude of K was attributed to the molecular volume and the size and distribution of NFRs' molecular surface electrostatic potential (MSEP). TBP and PBP with smaller molecular volumes exhibited evenly distributed positive and negative MSEP, facilitating their entry into the binding site and interact with HSA. In summary, this study elucidates the influence of pollutants' volume and the size and distribution of MSEP on the binding sites and K, providing a crucial theoretical basis for understanding the pollutants' potential human accumulation, which contributes to the screening and monitoring of new environmental pollutants.