Seafood has long been considered a healthy food choice, but it is also an exposure source of contaminants that may bring potential health risks to humans. Here, 80 organohalogen contaminants (OHCs) and 36 fatty acids (FAs) were analyzed in 22 (n = 211) and 19 fishery species (n = 176) from the eastern- and western Pearl River Estuary (PRE), respectively, for risk–benefit analysis. The average concentrations of total FAs in seafood from the eastern- and western PRE were 26.0 ± 2.14 and 21.3 ± 1.66 mg g−1 wet weight, respectively. Seafood from the eastern PRE exhibited higher levels of OHCs than those from the western PRE, highlighting the spatial heterogeneity of OHC contamination within the PRE. Species occupying higher trophic levels (TLs) typically demonstrated higher levels of OHC accumulation, indicating the biomagnification potential of these contaminants in the PRE ecosystem. Significant negative correlations were observed between TLs and the proportions of monounsaturated fatty acids and polyunsaturated fatty acids, presumably attributed to the ability of fish to synthesize these FAs decreases with increasing TLs. Our benefit-risk quotient (BRQ) analyses revealed that, as far as OHCs are concerned, all seafood species had a BRQ∑OHCs value <1, except for one-spot snapper and daggertooth pike conger, which had BRQ values of 1.03 and 1.14, respectively. The findings indicate that most marine species here analyzed may not pose significant health risks to consumers as a result of OHC exposure. However, considering that many other pollutants and nutrients are not analyzed here, the results of our risk assessments should be treated as preliminary, not final. Future data collection is essential to enhance the comprehensiveness of this type of analysis.
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