Table 3.

Referenced iron oxide nanoparticle in vivo studies.

Study	Animal	Particle	Primary Particle Size	Dose	Mode/Duration of Exposure	Time Points	Adverse Outcomes
[25] Park	ICR mice	Fe3O4	5.3 nm	0.25, 0.5, 1 mg/kg body weight	Intratracheal instillation	1, 7, 14, 28 days	Inflammation
[26] Park	ICR mice	Fe2O3	10 nm (209.4 nm agglomerate)	0.5, 1, 2 mg/kg body weight	Intratracheal instillation	90 days	Inflammation, Th1 polarized immune response
[27] Sadeghi	Wistar rats	Fe2O3	20 nm	20 or 40 mg/kg body weight	Intratracheal instillation (7 or 14 times, once every other day)	1 day post exposure set completion	Inflammation, liver damage
[28] Srinivas	Wistar rats	Fe3O4	15–20 nm	640 mg/m3	Inhalation, 4 h continuous	1, 2, 14 days	Inflammation
[31] Zhu	Sprague Dawley rats	Fe2O3	22 or 280 nm	0.8 or 20 mg/kg body weight	Intratracheal instillation	1, 30 days	Inflammation, pro-fibrosis, longer prothrombin and activated partial thromboplastin times
[32] Szalay	Wistar rats	Fe3O4	<50 nm	1 or 5 mg/kg body weight	Intratracheal instillation	1, 3, 7, 14, 30 days	Weak fibrosis
[33] Totsuka	ICR or gpt delta mice	Fe3O4	10–100 nm	0.05 or 0.2 mg/animal	Intratracheal instillation	3 h, 8 weeks	DNA damage in lungs, DNA adduct formation, inflammation, focal granuloma formation
[34] Ishino	ICR mice	Fe3O4	10–100 nm	0.2 mg/animal	Intratracheal instillation	1 day	DNA adducts (elevated ϵdC)
[45] Campbell	Mice (strain unknown)	Fe2O3·H2O	Unknown	0.5 g for 8–12 animals	Inhalation, 6 h/day continuous, 5 days/week, 1 year	Up to 800 days (or death of animal)	Primary lung tumors
[35] Zhu	Sprague Dawley rats	59Fe2O3	22 nm	4 mg/animal	Intratracheal instillation	Daily, up to 50 days	IONPs can pass into systemic circulation, and is distributed to mononuclear phagocyte rich organs
[36] Al Faraj	Balb/c mice	Fe2O3	129.3 nm	0.8 mmol iron/kg body weight	Intrapulmonary administration (once or three times on consecutive days)	2 h, 1 or 2 days, 1 or 2 weeks, 1 month	Particle translocation to liver, lipid peroxidation, DNA damage, inflammation biomarkers
[37] Wang	Wistar rats	Fe2O3	30 nm	8.5 mg/kg body weight	Dry powder nasal spray, twice daily for three days	Up to 36 h	Severe lung and liver tissue damage
[29] Ban	Balb/c mice	Fe2O3	35 or 147 nm	100, 250, or 500 μg/mouse	Intratracheal administration (four times) with or without OVA sensitization	24, 48 h after completion of exposure set	Inhibition of OVA-induced allergic response at high dose, enhancement with low dose
[30] Gustafsson	Balb/c mice	Fe2O3	30 nm	2.5 mg/kg body weight	Intratracheal instillation with or without OVA sensitization	1, 2, 7 days post exposure	Decreased inflammation with IONP and OVA attributed to excessive cell death in inflamed airways and lung draining lymph nodes
[55] Teeguarden	Balb/c mice	Super-paramagnetic IONPs	12.8 nm	19.9 mg/m3	Inhalation, four hour continuous	Up to 7 days	Particle deposition, interstitial inflammation, macrophage infiltration