Table 1.

Overview of Literature Investigating Neurotoxic Effects of TiO₂ NPs in Rats

Model System	Particle Size	Exposure Method	Exposure Time	Exposure Dose	Neurotoxic Effects	Ref.
Wistar rats	<30 nm	Intragastric administration, Intraperitoneal injection	GD 2–21	200 mg/kg	Oxidative stress, Altered expression of BDNF and IL-6	[49]
	10 nm	Intragastric administration	GD 2–21	100 mg/kg BW	Impaired memory, Decreased hippocampal cell proliferation	[46]
	<100 nm	Intragastric administration	GD 2–21 and PND 2–21	100 mg/kg BW	Apoptosis, Decreases neurogenesis	[50]
	10 nm	Intragastric administration	PND 0–21	0, 100 mg/kg	Impaired learning and memory	[44]
	5–10 nm	Intragastric administration	60 days	0, 50, 100, 200 mg/kg BW	Neuroinflammation response	[52]
	5–12 nm	Intragastric administration	Per week for 8 weeks	0, 50, 100, 200 mg/kg BW	Neuronal degeneration, Apoptosis	[53]
	32.34±2.37 nm	Intravenous injection	5 days	5 mg/kg BW	Motor functional damage, Mitochondrial dysfunction, Neuronal architecture alterations	[54]
	21 nm	Intravenous injection	/	2, 10 mg/kg BW	Oxidative stress, Neuroinflammation	[55]
	34 ± 9 nm	Intravenous injection	/	1, 5, 4, 16 g/kg BW	Cell apoptosis, Decreases neurogenesis	[56]
	/	Intravenous injection	Acute	20 mg/kg BW	Spatial cognitive impairments, Biochemical and structural changes	[57]
	28 nm	Intratracheal instillations	28 days	0, 1, 3, 10 mg/kg	Electrophysiological alterations	[58]
	15 x 65 nm	Intratracheal instillations	28 days	0, 5, 8, 10 mg/kg BW	Mitochondrial dysfunction, Oxidative stress, Cell apoptosis	[59]
	10,100 nm	Intratracheal instillations	30 days	5, 18 mg/kg BW	Motor functional damage	[60]
	20, 30 nm	Intraperitoneal injection	Every 2 days for 20 days	20 mg/kg BW	Increased anxiety index	[61]
	32.34 ± 2.37 nm	/	1 h	5, 10, 50 μg/mL	Mitochondrial dysfunction	[62]
SD rats	5 nm	Subcutaneous injection	GD 6, 9, 12, 15, 18.	1 μg/ μL	Depressive-like behaviors, Oxidative damage	[47]
	5 nm	Intravenous injection	30 days	0, 20 mg/kg	Oxidative stress, Neuroinflammation, Anxiety-like behavior, Cognitive dysfunction	[63]
	/	Intraperitoneal injection	28 days	0, 80, 120, 160 mg/kg	Oxidative stress, Histological alterations, Reduced cell viability	[64]
	170.9 ± 6.4 nm	Inhalation	GD 7–20	10.4 ± 0.4 mg/m3	Working impairments	[48]
	21 ± 5 nm	Intragastric administration	PND 2–5, PND 7–10, PND 17–20	0, 10 mg/kg BW	Damaged locomotor behavior, Perturbation of brain biochemistry	[45]
	<25 nm	Intragastric administration	GD 2–21	0, 2 mg/kg BW	Impaired synaptic plasticity, Oxidative damage	[51]
Fisher F344 rats	21.5 ± 7.2 nm	Inhalation	Per 5 days for 4 weeks	0, 10 mg/m3	Neuroinflammation, BBB dysfunction, Decreased neuronal synaptophysin	[65]
Albino rats	60 nm	Oral route	14 days	0, 150 mg/kg BW	Altered expression of neurobiomarkers	[66]

Note: The reported particle size reflects the diameter of primary particles.