Tissue-specific accumulation and integrated toxicological responses of the Pacific oyster, Crassostrea gigas, to chronic polyethylene microplastic exposure: An empirical toxicokinetic interpretation.

Microplastic (MP) bioaccumulation is increasingly recognized as a critical determinant of toxicological outcomes in aquatic organisms; however, the relationships between tissue-specific accumulation patterns and subsequent biological responses remain insufficiently understood. This study investigated polyethylene microplastic (PE-MP) bioaccumulation and associated toxicological responses in the Pacific oyster, Crassostrea gigas, under chronic exposure conditions (0-1000 μg/L) for 2 and 4 weeks. PE-MPs accumulated in a concentration-dependent manner and were consistently retained at higher levels in the digestive gland than in the gills. Empirical toxicokinetic interpretation indicated greater apparent accumulation rates and organ partitioning ratios in the digestive gland, suggesting preferential tissue retention during prolonged exposure. Multiple linear regression and random forest analyses further identified organ type, exposure duration, and exposure concentration as the primary determinants of internal PE-MP accumulation. Elevated accumulation was accompanied by coordinated alterations in hemolymph biochemical parameters, antioxidant defenses, and stress biomarkers, including increased glucose, AST, ALT, cortisol, SOD, CAT, and HSP70 levels, together with reduced total protein and calcium concentrations. Principal component analysis and integrated biomarker response analysis revealed clear concentration-dependent biological disturbances, particularly at 800 and 1000 μg/L. Collectively, these findings demonstrate that tissue-specific accumulation patterns are closely associated with integrated physiological, oxidative, and stress-related responses in C. gigas. The accumulation-based framework applied in this study highlights the value of incorporating bioaccumulation patterns into ecotoxicological assessments for improved interpretation of chronic MP toxicity in marine organisms.