Reactive carbonyl species in food systems: comprehensive review of formation pathways, toxicological mechanisms, and emerging health risk assessment frameworks

Reactive carbonyl species (RCS) represent a diverse class of electrophilic compounds ubiquitously present in environmental, dietary, and biological systems, posing significant challenges for human health risk assessment. This review systematically examines the classification, formation mechanisms, toxicological profiles, and health risk assessment frameworks for RCS, with particular emphasis on food-derived compounds. RCS are classified into 3 major categories: monocarbonyl compounds, polycarbonyl compounds, and α,β-unsaturated carbonyls. Each category exhibits distinct reactivity patterns and biological effects. These compounds are generated through both exogenous pathways, primarily during food processing, and endogenous metabolic processes, including lipid peroxidation, amino acid oxidation, and glycation reactions. RCS exert toxicity through multiple molecular mechanisms. These include protein carbonylation, DNA adduct formation, advanced glycation end product (AGE) generation, and disruption of cellular signaling pathways. Such molecular events contribute to the pathogenesis of diabetes, cardiovascular disease, neurodegeneration, and cancer. Human metabolism of RCS involves Phase Ⅰ reactions catalyzed by aldehyde dehydrogenases and aldo-keto reductases, followed by Phase Ⅱ conjugation via glutathione S-transferases. Genetic polymorphisms in these metabolic enzymes create substantial inter-individual variations in RCS susceptibility. Contemporary risk assessment approaches integrate classical food safety frameworks with mechanistic toxicology principles. Current methodologies employ benchmark dose modeling, cumulative exposure assessment, and biomarker-guided evaluation strategies. Future advancement of RCS risk assessment requires development of integrated assessment models, validation of exposure and effect biomarkers, application of physiologically-based pharmacokinetic (PBPK) modeling, and international regulatory harmonization through sustained interdisciplinary collaboration.