[Recent advances on environmental occurrence， risk and analytical methodologies of synthetic phenolic antioxidants]

Synthetic phenolic antioxidants （SPAs） are a major class of chemical additives extensively employed in plastics， rubber， and food packaging to prevent polymer degradation and extend product lifespans. In recent years， the environmental and human health risks of SPAs have received great concern due to their widespread occurrence in various environmental media. Existing reviews primarily focus on environmental detection， human exposure， toxicity， and risk assessment of SPAs with limited discussion on recent advances in analytical methodologies. This review presents a systematic synthesis of research advances over the past five years， especially the state of the art analytical methodologies. This review systematically analyzes their occurrence in water， sludge， sediments， soils， dust， and biota tissues， revealing a clear pollution transition from conventional SPAs to emerging high-molecular-weight substitutes. Toxicological evidence demonstrates that SPAs exert adverse effects on rats， mice， and aquatic organisms， including genotoxicity， immunotoxicity， endocrine disruption， reproductive toxicity， etc. Notably， certain transformation products （TPs） of butylated hydroxytoluene （BHT） exhibit enhanced toxicity relative to their parent compounds. Methodological advances in sample preparation and analysis techniques of SPAs in different environmental matrices are reviewed for the first time. Recent applications of atmospheric pressure chemical ionization coupled with liquid chromatography-tandem mass spectrometry （APCI-LC-MS/MS）， as well as high-resolution mass spectrometry （HRMS） provide powerful approaches for target/non-target analysis of unknown SPA derivatives and TPs. Several critical research gaps have finally been identified. Environmental analytical methods of SPAs and their TPs face significant challenges due to their diverse physicochemical properties and chemical reactivity， particularly their susceptibility to oxidation. Another key issue is that current pretreatment approaches for SPAs in tissue samples overlook bound-SPAs， thereby underestimating their real body burdens. Moreover， existing studies mainly focus on traditional SPAs， while lacking systematic assessment of environmental fate and long-term ecological risks posed by emerging SPAs and potentially more toxic TPs. Additionally， ecotoxicological data of SPAs for terrestrial organisms are scarce compared to aquatic organisms and mammals， limiting comprehensive ecological risk assessment. Future research should prioritize： （1） developing oxidant-resistant pretreatment methodologies coupled with HRMS to overcome technical challenges in accurate quantification of trace SPAs and their bound species； （2） strengthening non-target screening and identification of emerging SPAs and TPs； （3） investigating long-term effects of SPAs in soil-plant-microorganism systems. This review advances our understanding of SPAs by bridging the knowledge gaps and providing updated insights into current research. It will help establish the scientific basis for comprehensive ecological risk assessment of SPAs.