Acute oral dose toxicity study of micro- and nano-plastics of polystyrene in female Wistar albino rats.

Human exposure scenarios to emerging pollutants, micro- and nanoplastics are increasing. However, in vivo reports defining their acute genotoxic hazard, particularly under combined (microplastics (MPs) + nanoplastics (NPs)) exposure are limited. Polystyrene (PS) MPs and NPs are among the most prevalent and are being detected in food and environmental matrices. Hence, we investigated the acute genotoxic effects of PS MPs, NPs, and MPs+NPs treatment following oral administration at 10, 100, and 1000 mg/kg body weight doses in female Wistar rats. Particle characterization confirmed polymer integrity and size distribution, with hydrodynamic diameters of 1422 nm for MPs and 112.3 nm for NPs in Milli-Q water. A dose-dependent hepatic and renal injury was observed in histopathological studies and the effect was more prominent at the 1000 mg/kg dose in rats treated with PS MPs+NPs. Comet assay results showed significant DNA damage in peripheral blood leukocytes, bone marrow, liver, and kidney cells with PS NPs and MPs+NPs compared with PS MPs treatment alone. Notably, PS MPs+NPs exposure induced DNA damage even at the lowest dose (10 mg/kg) tested. Cell cycle analysis in rats treated with PS MPs and NPs depicted arrest in G0/G1, S, and G2/M phases which was consistent with activation of DNA damage checkpoints. A dose dependent elevation in Thiobarbituric acid reactive substances (TBARS) levels levels and depletion of reduced glutathione in plasma samples of rats indicate disruption of redox homeostasis. Overall, the findings of this study provide invaluable insights on PS plastic particles in vivo effects after acute oral exposure indicating oxidative stress mediated DNA damage, cell cycle perturbation, and tissue injury. The overall toxicity trend followed the order MPs+NPs > NPs > MPs, suggesting enhanced toxicity following combined exposure and highlighting the need for long-term toxicity studies of MPs+NPs mixtures to inform regulatory risk assessment.