Oil‐Coated Nanoplastics Induce Rapid Membrane Disruption and Severe Intestinal Injury

ABSTRACT Plastic food containers used in food delivery may pose underrecognized health risks by releasing micro‐ and nanoplastics (MNPs), especially when in contact with oil‐rich foods. Here, we show that cooking oil dramatically increased MNP release from polypropylene (PP) and polyethylene (PE)‐coated containers within 3 min of microwave heating, reaching up to 1.52 × 10 ¹⁴ particles/L, approximately 125‐fold higher than with water. Concurrently, the co‐release of plastic additives and heavy metals increased by up to 309‐fold. Soybean oil‐derived PP nanoplastics were four times more cytotoxic (IC ₅₀ = 18.7 µg/mL) than water‐derived particles (IC ₅₀ = 77.1 µg/mL), likely due to oil‐film coatings, a positive surface charge (+7.37 mV), altered surface properties, and co‐extracted additives. Fluorescence and transmission electron microscopy revealed rapid membrane disruption within 5 min of exposure at 100 µg/mL. In vivo, oral exposure of mice to oil‐derived nanoplastics (50 mg/kg) for two weeks caused severe intestinal barrier damage and mucosal immune dysfunction. These adverse effects were partially alleviated by immune‐ and barrier‐targeted interventions. Benchmark dose modeling established safety thresholds of 0.4 µg/mL at the molecular level and 15.83 mg/kg for tissue injury. Alarmingly, modeled five‐year gastrointestinal burdens and reported human tissue MNP levels exceeded molecular safety thresholds by up to 1107‐fold, though not tissue injury thresholds. These findings highlight the urgent need for stricter regulations on oil‐contact plastics and the development of safer food packaging materials.