Dose-Dependent Hepatic and Renal Response to Repeated Oral Exposure to Polyethylene Nanoparticles in Male Wistar Rats

Abstract

Polyethylene (PE) is widely used, but organ-specific toxicity data for small PE particles remain limited and particle-size dependent. This study evaluated hepatic and renal responses to repeated oral exposure to an ultrasonically generated PE nanoplastics-enriched suspension in male Wistar rats. Particle-metric analysis identified 134 particles with Feret diameters of 35.35 nm–7.33 µm, a median of 83.08 nm, and a mean of 280.50 nm; 94.8% were ≤100 nm and 97.0% were ≤1 µm, indicating nanoscale predominance by number within a polydisperse preparation. Twenty-five rats (90–135 g) were randomized into five groups (n = 5): one control and four groups receiving an 80 mg/mL PE suspension by oral gavage once daily for 28 days at fixed volumes corresponding to initial target doses of approximately 17.5, 35.0, 70.0, and 140.0 mg/kg/day. Serum hepatic and renal indices and electrolytes were assessed, liver and kidney tissues underwent haematoxylin-and-eosin examination. At the highest exposure, ALT, AST, ALP, GGT, and total bilirubin were 556%, 276%, 112%, 129%, and 73% above control, respectively. Albumin decreased significantly in Groups 2–4 (p<0.05), while total protein was lowest in Group 3. Creatinine increased significantly at 70 and 140 mg/kg/day by approximately 15% and 27%, respectively (p<0.05). Urea, sodium, and chloride remained unchanged, whereas potassium increased significantly (p<0.05) and bicarbonate rose modestly at the two highest exposures. Histological examination revealed exposure-associated hepatic and renal abnormalities, most apparent at higher exposures. These findings indicate pronounced, dose-related hepatic injury and comparatively more modest renal impairment accompanied by structural tissue alterations.