Beyond total arsenic: rethinking seafood-related arsenic risk assessments

Seafood is an important component of human nutrition worldwide but also represents a major dietary pathway of arsenic (As) exposure. Assessing seafood-related health risks remains challenging because As toxicity depends strongly on chemical speciation rather than total concentration alone. Although seafood often contains high total arsenic (tAs), most occurs as organic compounds such as arsenobetaine, generally regarded as low in toxicity and rapidly excreted in humans. In contrast, inorganic arsenic (iAs), primarily arsenite [As(III)] and arsenate [As(V)], is highly toxic and carcinogenic. Emerging evidence further challenges the traditional assumption that organic arsenicals are uniformly harmless, as methylated intermediates have demonstrated cytotoxic and genotoxic properties, and some arsenolipid subclasses, particularly arsenic-containing hydrocarbons, have demonstrated cytotoxicity. Despite the importance of As speciation assessments, routine species-specific analysis remains limited in seafood monitoring due to the limited availability of validated methods and certified reference materials, as well as relatively high operational costs, and limited laboratory accessibility. Consequently, many exposure assessments rely on tAs concentrations and generalized assumptions regarding iAs fractions, despite substantial variability among seafood taxa, habitats, and geographic regions. Human exposure assessments are further complicated by marked differences in seafood consumption patterns and demographic susceptibility, with coastal and fishing-dependent communities often experiencing substantially greater dietary exposure than population averages suggest. This review synthesizes current knowledge on As occurrence and speciation in seafood, analytical approaches, toxicological implications of different arsenic species, and human exposure and risk assessment frameworks, including Estimated Daily Intake (EDI), Estimated Weekly Intake (EWI), Target Hazard Quotient (THQ), Hazard Index (HI), and Target Cancer Risk (TCR). Particular emphasis is placed on taxonomic variability in iAs occurrence, localized seafood consumption, demographic heterogeneity, and emerging toxicological evidence. Collectively, the evidence supports a transition from tAs-based screening toward more realistic, speciation-informed and context-dependent seafood risk assessment.