Regular exposure to low dose of diarrheic shellfish toxins: Implications for the seafood consumer

Diarrhetic shellfish toxins (DSTs) are marine biotoxins produced by the dinoflagellates Dinophysis and Prorocentrum that cause gastrointestinal illness in humans worldwide. While European legislation avoids the risk of acute poisoning, the toxicity associated with repeated dietary exposure to DSTs in low quantities remains incompletely characterized. To address knowledge gaps regarding long-term exposure, we evaluated the toxicity of okadaic acid (OA), dinophysistoxin-1 (DTX1) and dinophysistoxin-2 (DTX2) administered by voluntary ingestion to male and female mice. Toxins were administered for 28 days at an experimentally calibrated dose (90 μg/kg bw) modelling a repeated human dietary exposure scenario derived from regulatory thresholds. Water consumption progressively decreased in treated females; the OA and DTX2 group also exhibited an increased urine protein-to-creatinine ratio, and minor histological renal changes. Repeated administration of DTX1 resulted in the most frequent diarrhea episodes and severe macroscopic damage to the digestive tract. Conversely, DTX2 produced the mildest clinical profile and lowest tissue retention. Furthermore, fecal toxin patterns differed by toxin: OA showed high initial excretion, DTX2 reached the highest fecal levels, and DTX1 was scarcely detected. Our findings indicate that repeated exposure to sublethal doses of DSTs by voluntary ingestion is associated with analogue- and sex-dependent persistent gastrointestinal alterations and subtle organ sensitivity, suggesting potential cumulative effects, which warrants further evaluation within risk assessment frameworks.