Environmentally relevant doses of polyethylene microplastics exposure induce 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. The dosing regimen was designed based on the environmentally relevant exposure levels, with 34-μm PE-MPs administered orally to male rats via daily gavage for 28 consecutive days at 0.6, 6.0, and 60.0 mg/kg bw. 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 10 and 100 times the environmentally relevant dose levels. 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 offers the first systematic evidence of environmentally relevant PE-MPs-induced thyroid toxicity, establishing thyroid gland as the primary target organ by integrating toxicokinetics with multi-omics profiling, yielding a comprehensive exposure-toxicity relationship and pinpointing key genes as critical biomarkers for future monitoring of environmental microplastic exposure and early health effects. These findings provide crucial scientific data on PE-MPs for future human health risk assessment and regulatory decisions.