Incorporating bioaccessibility into human health risk assessment of halogenated flame retardants: from external exposure to bioaccessible dose.

Halogenated flame retardants (HFRs) are persistent contaminants of global concern. Current assessments of the human health risks of HFRs largely rely on total environmental concentrations, which reflect external exposure rather than the fraction available for uptake. Addressing this limitation requires bioaccessibility, defined as the fraction released from an ingested matrix and made available for absorption, distinct from bioavailability and internal dose. Despite its relevance, bioaccessibility has not been systematically integrated into HFR risk assessment. Based on evidence from 176 studies, this critical review evaluates how bioaccessibility can refine exposure estimation for legacy and alternative HFRs. HFRs are widely detected in water, soil, dust, air, and food. While BDE-209 remains dominant, alternatives such as DBDPE and BTBPE show increasing occurrence with regional variability. Human exposure occurs mainly via dietary intake, dust exposure, and dermal contact, with infants and e-waste workers at higher risk. Bioaccessibility varies markedly (11-94%) depending on physicochemical properties (e.g., log KOW), matrix characteristics, and digestive conditions. Highly brominated congeners (e.g., BDE-209) generally show low bioaccessibility (<30%), and plastic-bound HFRs are less bioaccessible than dust-associated forms. Cooking can further reduce bioaccessibility. Toxicological evidence links HFR exposure to endocrine disruption, multi-organ toxicity, reproductive effects, and neurodevelopmental deficits. Overall, this review integrates environmental occurrence, exposure pathways, and toxicity within a unified framework. It identifies methodological inconsistencies in bioaccessibility assessment as a key limitation and calls for standardized in vitro approaches. Incorporating bioaccessibility into risk assessment enables a shift from total concentration-based evaluation to bioaccessible dose-based assessment, supporting more accurate regulation and mitigating the cycle of regrettable substitutions.