Pulmonary toxicity of micro- and nano polyethylene particles following intratracheal instillation in rats

BACKGROUND: Micro- and nano-sized polyethylene plastics (PE-MPs and PE-NPs) are emerging as potential risk factors for pulmonary disease and risk assessment. Currently, their is no direct evidence suggests this appreciable health risk extends to humans. Furthermore, the toxicological evaluation of PE-MPs and PE-NPs is insufficient to support their safe use. METHODS: This study was aimed to characterize the toxicity of PE-MPs and PE-NPs after 13 weeks of intratracheal instillation in Sprague-Dawley (SD) rats and to assess the reversibility of any effects during a 4-week recovery period. Exposure levels for PE-MPs and PE-NPs were set at 0, 40, 80, and 120 μg per rat once a week. RESULTS: The results indicated that the treatment administration resulted in observable lung tissue alterations. Inflammatory cells were present in the perivascular and peribronchiolar regions in both sexes at ≥ 40 μg per rat in the PE-MPs and PE-NPs-treated groups, indicating a biological response that can turn into toxicity. Additionally, thickened alveolar ducts and alveolar epithelial hyperplasia were noted in males at 120 μg per rat PE-MPs, in males at ≥ 80 μg per rat PE-NPs, and in females at ≥ 40 μg per rat PE-MPs and PE-NPs-treated groups. Interestingly, when instilled repeatedly with both sizes of polyethylene particles, IL-1β and TNF-α secretion was significantly more enhanced in female rats compared to male rats. At the same time, the pulmonary level of IL-6 increased more clearly in male rats than in female rats. The pulmonary level of C-reactive protein, a marker for acute inflammation, was increased in all treated groups. CONCLUSION: These findings suggest that the lowest-observed-adverse-effect level (LOAEL) for PE-MPs and PE-NPs based on repeated exposures is below 40 μg per rat for both sexes. However, the toxicological data for PE-MPs and PE-NPs remain insufficient to confirm their safety, and further research is necessary to evaluate their potential risks to human health.