Repeated oral exposure to polyethylene microplastics induces thyroid toxicity in rats: Evidence from in vivo toxicokinetics and multi-omics analyses

The widespread use and non-biodegradable nature of polyethylene microplastics (PE-MPs) have prompted significant public concern about their safety. However, the mechanisms underlying their adverse effects on human health remain largely elusive. Male rats were orally administered 34-μm PE-MPs via daily gavage for 28 consecutive days, with three dose groups set at 0.6, 6.0, and 60.0 mg/kg body weight (bw), respectively. The results showed that exposure to PE-MPs induced a decrease in serum triiodothyronine (T3) levels, accompanied by an increased incidence of thyroid follicular dilation, both of which displayed a distinct dose-response relationship. The 28-day oral toxicity study in male rats identified a no-observed-adverse-effect level (NOAEL) of 0.6 mg/kg bw and a lowest-observed-adverse-effect level (LOAEL) of 6.0 mg/kg bw for PE-MPs, corresponding to approximately 10 and 100 times the estimated daily human intake of microplastics, respectively. Toxicokinetics revealed that PE-MPs were absorbed and markedly accumulated in major organs, and the organ burdens correlated strongly with the severity of thyroid toxicity. Integrative multi-omics analysis implied that PE-MPs exposure altered the expression of thyroid toxicity-related genes Ddit3, Zbtb16 and the levels of associated metabolites. This study provides exploratory experimental evidence identifying the thyroid as a target organ for PE-MPs-induced toxicity. It should be noted that conclusions drawn from multi-omics and toxicokinetic analyses are limited by the relatively small sample size in the present work. Further validation with larger sample sizes is required in future studies. These findings contribute valuabledata to human health risk assessment and regulatory oversight of PE-MPs.