*4.1. Inhalational-Based Toxicity*

MPs and NPs in the air mainly enter animals and humans through inhalation and first contact with the respiratory system. Due to the clearance mechanisms of the respiratory barriers (such as the nasal cavity, trachea, the bronchus, and alveolar macrophages), a

considerable proportion of these plastic particles cannot enter the body and form deposition, and the deposition coefficient is mainly affected by the particle size, density, etc. [49]. Smaller nanoparticles (<2.5 μm) can avoid the clearance mechanism and penetrate the lung and respiratory barrier [19,68–70]. Macrophages can deposit plastic particles in the respiratory system, remove these from the respiratory system, or help them migrate in the respiratory system and allow them to enter the circulatory system, leading to dust metastasis. Further, the presence of MPs and NPs in the respiratory system and their large surface area can also lead to the release of chemokines that affect the migration of macrophages, resulting in particle overload [68]. The influx and inflammation of neutrophils associated with polystyrene granules (64 nm) in rat lungs, as well as the expression of pro-inflammatory genes in epithelial cells, are caused by granule-induced oxidation [71]. Due to the large specific surface area of MPs, a large number of oxidizing substances (such as metals) will be adsorbed on the surface of MPs, which may produce excessive reactive oxygen species and lead to excessive antioxidant reaction in vivo, namely oxidative stress [72,73].

There are only a few pieces of research on the toxic effects of atmospheric MPs on animals and humans. Inhalation of MPs has the most significant toxic effects on the respiratory system. Studies have shown that PVC prepared by emulsion polymerization (2 mm) has significant cytotoxic and hemolytic effects on rat and human lung cells in vitro [74]. Xu et al. 2002 [74] evaluated the toxic effects of PS-NPs on human alveolar epithelial cells and found that PS-NPs can rapidly internalize into cells; significantly reduce cell viability; affect cell cycle and apoptosis, as well as related gene transcription and protein expression; and promote inflammatory response. The smaller the diameter, the faster the corresponding velocity. Lim et al., using metabonomics to investigate the toxic effects of PS-NPs on bronchial epithelial cells, found that nanoparticles interfere with cell energy metabolism, accompanied by oxidative stress, and mediate the increase of intermediate metabolites to reduce cell resistance to toxicity [75]. Dong et al. found that PS-MPs can induce cytotoxicity and inflammation in human lung epithelium by inducing reactive oxygen species formation. Low concentrations of PS-MPs disrupt the lung barrier, while high concentrations of PS-MPs also induce decreased levels of α 1-antitrypsin, which increases the risk of chronic obstructive pulmonary disease [76]. Paget et al. explored particle internalization and cell damage after aminated PS-NPs acted on human lung epithelial cells and macrophages. Cells in the experimental group showed high glutathione depletion, excessive reactive oxygen species, and significant DNA damage. It is suggested that microand nanoplastics may exhibit strong genotoxicity when absorbed and internalized by the respiratory system [77]. In in vitro experiments, seven functional groups with different charges were added to an aminated PS-NPs and eight PS-NPs, including the original particles, were sent into different rats by pharyngeal aspiration. Most of the particles were phagocytized by alveolar macrophages and showed different acute lung inflammation. The particle potential showed excellent correlation with pneumonia-related parameters, indicating that surface charge is a key factor affecting lung inflammation induced by microand nanoplastics [78].

Respiratory lesions have been found in workers exposed to synthetic textiles, fusing, vinyl chloride, or PVC, which is quite different from the general population [79–83]. Inhaled MPs and NPs are not easily cleared by the human lungs, and they may stay in the lungs for a considerable period, which can cause an inflammatory response in the lungs [53]. It is reported that artificial glass fiber can cause DNA damage, which can induce cancer [84]. In short, Inhaling MPs can have toxic effects on animals and humans.
