Table 3.

Nanoplastics induced toxicological endpoints based on mammalian studies.

Organisms		Nanoplastics		Exposure		Endpoints			Other major results	Reference
Species	Cell/Tissue type	Plastic type and size	Surface modification	Concentration/Dose	Exposure duration	Molecular and cellular (MIE/KE)	Tissue and organ KEs	Individual or population AO
Wistar rats	Whole body	PS NPs 38.92 nm	Plain PS NPs	1, 3, 6, and 10 mg PS-NPs/kg of body weight/day	35 days	Not stated	Not stated	may exacerbate behavioral effects	The uptake of pristine nanoparticles did not affect behavior of adult rats	[82]
Wistar rats	Whole body	25 and 50 nm, PS NPs	Plain PS NPs	1, 3, 6, and 10 mg PS-NPs/kg of body weight/day	35 days	high-density lipoprotein level blocked	Not stated	thyroid endocrine disruption	PS treatments significantly increased serum LDL, cholesterol, GOT, and GPT levels notably	[19]
Human and mouse	human bronchial epithelium (BEAS-2B), mouse monocyte macrophage (RAW 264.7)	PS NPs 60 nm	Plain PS, PS-NH2, PS-COOH	10–25 mg/L	1–8 h	lysosomal permeability increased in RAW 264.7 after PS-NH2 exposure	Not stated	Not stated	The cationic PS nanospheres had no effect on cellular toxicity in HEPA-1, HMEC, and PC-12 cells	[70]
						Ca2+ influx increased in RAW 264.7 after PS-NH2 exposure
						Apoptosis
						Mitochondrial disruption
Human	colon carcinoma cells (Caco-2)	PS NPs 20–40 nm	Plain PS, PS-NH2, PS-COOH	0.3, 0.9, 2.0, 4.0, and 6.6 nM	4–16 h	Cell viability hampered	Not stated	Not stated	the uptake efficiency is surface charging and size dependent	[85]
						Oxidative stress leading apoptosis
Human	alveolar epithelial type 1, 2 cells (TT1, AT2), primary alveolar macrophages (MAC)	PS NPs 50–100 nm	Plain PS, PS-NH2, PS-COOH	1–100 mg/L	4 and 24 h	PS-NH2 induced apoptosis in all cell types	Not stated	Not stated	Plain PS, PS-COOH exhibited little cytotoxicity or mitochondrial damage, although they induced ROS; TT1 and MAC cells internalized all NP formats, whereas only a small fraction of AT2 cells internalized PS-NH2	[71,104]
						All NPs induced ROS induction
						PS-NH2 induced mitochondrial disruption and release of cytochrome C
Human	monocytic leukemia cell line THP-1, histocytic lymphoma cells U937	PS NPs 20, 100, 200, 500, 1000 nm	PS-COOH	10, 20 and 50 mg/L	30 mis to 24 h	PS-COOH induced cytokine production (IL-8, IL-6)	Not stated	Not stated	Twenty nanometers CPS were cytotoxic to all phagocytes, ≥500 nm CPS particles only to macrophages. 20 nm particles were taken up passively, 100−1000 nm actively and passively.	[14]
						20 nm PS-COOH induced Oxidative stress
						PS-COOH stimulated myeloperoxidase release of granulocytes and nitric oxide generation in macrophages
Human	Calu-3 epithelial cells, monocytic leukemia cell line THP-1	PS NPs 50 nm	Plain PS, PS-NH2, PS-COOH	1–100 mg/L	1–24 h	PS-NH2 nanobeads induced DNA double strand breaks	Not stated	Not stated	Particles partly adsorbed and internalized then released by Calu-3 cells; THP-1 macrophages quickly incorporated all nanobeads. Surface modification matters in the nanotoxicology.	[60]
						GSH depletion, antioxidant hamper
Human	colon carcinoma cells (Caco-2, LS174T, HAT-29)	PS NPs 57 nm	Plain PS, PS-NH2, PS-COOH	20, 50, and 100 μg/mL	72 h	Induction of apoptosis by PS-NH2	Not stated	Not stated	Positively Charged Polystyrene NPs Reduce Cell Viability; binding of mucin	[89]
Human	Monocyte macrophages	PS NPs; 120 nm	Plain PS, PS-NH2, PS-COOH	100 μg/ml	24 h	Nanoplastics impaired expression of scavenger receptor (CD163 and CD200R) in M2	Not stated	Not stated	The nanoparticles did not compromise macrophage viability nor did they affect the expression of the M1 markers CD86, NOS2, TNF-α, and IL-1β.	[83]
						Nanoplastics impaired the release of cytokines (IL-10) in M2
						Frustrated phagocytosis by PS-NH2
						PS-COOH increased ATP level in M2
Human	Gastric adenocarcinoma (AGS) cells	PS NPs, 44 and 100 nm	Plain PS	2, 5, 10, 20 and 30 μg/ml	1–24 h	Cytokine genes expression increase (IL-6 and IL-8)	Not stated	Not stated	NPs in smaller size accumulate rapidly and more efficiently in the cytoplasm of AGS than bigger size; energy dependent mechanism of internalization and a clathrin-mediated endocytosis pathway	[88]
						Up Regulation, TGFbeta1 expression
Human	ovarian cancer cells	PS NPs 10–30, 50 nm	Plain PS, PS-NH2, PS-COOH	10–75 μg/ml	1–8 h	PS-NH2 accumulated within lysosomes	Not stated	Not stated	Polystyrene nanoparticle uptake occurred via a caveolae-independent pathway, and was negatively affected by serum	[74]
						cell death
Human	lung adenocarcinoma cells (A549)	PS NPs 64, 202, 535 nm	Not stated	250 μg/ml or 2 mg/ml	2–24 h	Increased cytokine production	Not stated	Not stated	Ultrafine polystyrene particles also stimulated the entry of extracellular calcium on treatment with thapsigargin	[90]
Rat	Whole body				24 h	lactate dehydrogenase increase	Neutrophil influx (Infiltration, Inflammatory cells)	Not stated
							Inflammation