Table 2.

Summary of the toxicological studies on the adverse health effects of ambient UFPs.

Targeting system	PM source or material	Particle size	Animal model	Exposure method	Effect	Potential toxicological mechanisms	Reference
Respiratory system	Ambient sampling	188 nm (average)	BALB/c mice	Nasal instillation	Chronic pneumonia	Il-6, Il-1b, Il-10 increase Cyp1a1, Cyp1b1 increase	[10]
	CuO NPs	200 nm (average)	C57BL/6 mice	Intratracheal instillation	Acute lung injury	T cell subset imbalance	[134]
	CB NPs	40 nm (average)	C57BL/6 mice	Whole-body exposure	Small airway obstruction	CC16 decrease SP-A increase	[135]
	Ambient sampling	50 nm (average)	C57BL/6 mice BALB/c mice	Whole-body exposure	Offspring pulmonary immunosuppression	Th2-driven pulmonary inflammation decrease	[19]
Cardiovascular system	DEP	24 nm (average)	Rat cardiomyocytes	Cellular contamination	Cardiomyocyte dysfunction	The reduction in contractility and calcium handling in cardiomyocytes	[36]
	Ambient sampling	<100 nm	Sprague Dawley rat	Intratracheal instillation	Cardiac I/R injury	mPTP Ca2+ Sensitization	[136]
	Ambient sampling	76 nm (average)	C57BL/6 mice	Whole-body exposure	Cardiac arrhythmias	GTR decrease Cardiac contractility decrease	[29]
	Ambient sampling	<60 nm	C57BL/6 mice	Intratracheal instillation	Offspring hypertension	Alterations in methylation of promoter regions of RAS-related elements	[33]
	Road traffic	<180 nm	ApoE−/− mice	Whole-body exposure	Atherosclerosis	Activates the Nrf2 signaling	[34]
	Road traffic	45 nm (average)	Ldlr−/− mice	Whole-body exposure	Vascular calcification	Activates the NF-κB signaling	[37]
	Road traffic	45 nm (average)	Ldlr−/− mice	Whole-body exposure	Atherosclerosis	Lipid metabolism and HDL dysfunction	[35]
	Ambient sampling	<100 nm	C57BL/6 mice	Thoracic aorta exposure	Impaired vasomotor responses	Oxidative stress Loss of anti-oxidant defenses	[137]
Digestive system	CB NPs	100 nm (average)	C57BL/6 mice	Oral administration	Acute hepatitis	ROS, CAT increase	[42]
	CB NPs	51 nm (average)	C57BL/6 mice hepatocytes	Cellular contamination	Hepatocytes apoptosis	ROS increase Lipid peroxidation increase	[44]
	CB NPs	35 nm (average)	C57BL/6 mice	Intravenous injection	Hepatic genotoxicity	Oxidative DNA damage	[47]
	Road traffic	82 nm (average)	Ldlr-null mice	Whole-body exposure	Gastrointestinal inflammation	The levels of oxidized fatty acids and LPA in intestine increase	[50]
	Road traffic	45 nm (average)	Ldlr−/− mice	Oral administration	Intestinal microbial composition disorders	LPC 18:1 level increase	[51]
	Ambient sampling	66 nm (average)	C57BL/6 mice	Whole-body exposure	Lipid metabolism disorders	Activate the FXR/LXR and Hnf4a signaling	[52]
Central nervous system	Ambient sampling	Natural occurreda	C57BL/6 mice	Whole-body exposure	AD	Amyloid deposition, tangles, and plaque increase	[54]
	Fuel combustion	178 nm (average)	C57BL/6 mice	Whole-body exposure	AD	Perturbation in hippocampal redox homeostasis	[59]
	Road traffic	83 nm (average)	3xTgAD mice	Whole-body exposure	AD	Neuroinflammation	[60]
	BB and DEP	<50 nm	BALB/c mice	Intratracheal instillation	Neurodegeneration	HO-1, Hsp70, Cyp1b1 increase iNOS, COX-2 increase	[62]
	Diesel Exhaust	<100 nm	Fischer rats	Whole-body exposure	Neuroinflammation	TNFα, α Synuclein, Aβ42 increase Tau hyperphosphorylation	[63]
	Ambient sampling	Natural occurreda	B6C3F1 hybrid mice	Whole-body exposure	Neurodevelopmental disorders	Enlarged brain ventricles, increased corpus callosum area, decreased hippocampal	[64]

Aβ42, β-amyloid (1–42); BB, biomass burning-derived; CC16, clara cell secretory protein; COX-2, cyclooxygenase 2; Cyp1b1, Cytochrome P450 1b1; DEP, diesel exhaust particles; FXR, farnesoid X receptor; GTR, glutathione S-transferase; Hnf4a, hepatocyte nuclear factor 4 alpha; HO-1, heme oxygenase-1; Hsp70, heat-shock protein 70; I/R, cardiac ischemia/reperfusion; iNOS, inducible nitric oxide synthase; LPA, lysophosphatidic acids; LPC 18:1, lysophosphatidylcholine; LXR, liver X receptor; mPTP, mitochondrial permeability transition pore; RAS, renin-angiotensin system; SP-A, lung surface viability protein A; Tau, microtubule-associated protein tau; TNFα, tumor necrosis factor-α.

^aParticle size is not presented in this study.