Table 3.

Overview of TiO₂ inhalation data in the literature

Animal species	TiO2 size (nm)	Form	Doses	BET surface area (m2/g)	Deposited dose and calculated deposited surface area (m2/animal)	Inflammation (neutrophils increased in BAL fluid at end of exposure)	Genotoxicity/ carcinogenicity	Reference
Mouse	10, but reported to be aggregated	Anatase	271 mg/m3 for 1 h	173	Estimated deposited dose (by authors): 91 µg	No (assessed 24 h after exposure)	Yes in lung tissue	(32)
					Estimated deposited surface area: 160 cm2
Mouse	Anatase crystallite size: 41 nm and brookite size 7 nm, but particles consisted of agglomerates of 10–60 nm crystallites with an average primary particle size of 21 nm	74% anatase, 26% brookite	5 days, 4 h/day at 0.8, 7.2 or 28.5 mg/ m3	61	Measured retained TiO2 per animal 2.7, 18 and 84 µg	Yes at highest dose (assessed immediately after exposure)	No effect on DNA damage	(31)
					Deposited surface areas: 2, 10 and 50 cm2
Rat	5 nm, but when tested showed large agglomerates >100 nm, and small aggregates <100 nm	<10% rutile, >90% anatase	6 h at 2 or 7 mg/m3	210	Calculated lung burden (by authors) 14 and 51 µg	Yes at high dose but only with large aggregates (assessed 16 h after exposure)	Not measured	(30)
					Estimated deposited surface areas: 30 and 100 cm2
Rat	Anatase phase particles were 52 nm and rutile phase particles were 61 nm, but in article measured and reported to be 79 nm	5.5% rutile, 94.5 (not written directly in article) of anatase	2 weeks, 6 h/day for 5 days/week at 11.4 mg/m3	Not reported but estimated to be 20 based on TiO2 surface areas reported in other studies (07,29–33,57,67–69)	Estimated delivered dose (by authors): 10.3 mg/rat	No effect (assessed 24 h after exposure)	Not measured	(28)
					Estimated deposited surface area: 2000 cm2
Rat	25 ± 8	14% rutile, 86% anatase	2, 10 or 50 mg/ m3 6 h/ day for 5 days	51	Measured lung burden TiO2 118, 545 and 1635 µg/lung (by current authors considered to be per 2 lungs)	Effect at two highest doses (assessed at the day of the last exposure)	Not measured	(29)
					Deposited surface areas: 60, 300 and 800 cm2
Rat	Mass median aerodynamic diameter of 1.1 µm. The used particle, Bayertitan T, has a size of 1800 nm (70)	99.5% rutile	5 mg/m3 for 18 h per day, 5 days/week for up to 24 months	1.9	Reported retained mass 2.7 mg/lung	Not measured	Tumours were investigated, but no differences found	(34)
					Deposited surface area 50 cm2
Rat	15–40 nm, mass median aerodynamic diameter was ~1.5 µm	P25, CAS no. 13463- 67-7, 80% anatase and 20% rutile	18 h/day, 5 days per week for up to 24 months (7.2 mg/m3 for first 4 months and then 14.8 mg/ m3 for 4 months, and 9.4 mg/m3 for 16 months)	48	Retained mass in rat at 24 months: 39 mg	Not measured	Lung tumours were increased	(33)
					Deposited surface area in rat: 19000 cm2
Rat	25	Aeroxide P25 80% anatase, 20% rutile	13 or 33 mg/ m3 for 4 h	57	Lung burden of 44 or 170 µg	Effect at highest dose (assessed 20 h after exposure)	Not measured	(07)
					Estimated surface area deposited:
					Low dose: 25 cm2
					High dose: 100 cm2
Rat and mouse	21	P-25 particles (ratio between rutile and anatase not reported)	0.5, 2 or 10 mg/ m3 6 h/day, 5 days/ week for 13 weeks	Not provided, estimated to be 50 based on refs (07,29–33,57,67–69)	Deposited doses:	Yes, effect but only at highest dose (assessed immediately after exposure)	Not measured	(57)
					High-dose rat: 11 mg/g dried lung = 1.7 mg/ lung (a female rat dried lung weight of 150 mg was used)
					Mid-dose rat: 1.4 (rat) = 0.2 mg/lung
					High-dose mouse: 11 mg/g dried lung = 0.2 mg/lung (a female mouse dried lung weight of 17 mg was used)
					Mid-dose mouse: 1.7 (mouse) mg/g dried lung weight = 0.03 mg/lung
					Estimated surface area in the lungs:
					Mid-dose rat: 100 cm2
					High-dose rat: 850 cm2
					Mid-dose mouse: 15 cm2
					High-dose mouse: 100 cm2
Rat	21		125 mg/m3 for 2 h	Not provided, estimated to be 50 based on refs (07,29–33,57,67–69)	Determined lung burden: 765 µg	Yes, effect	Not measured	(71)
					Estimated surface area dosed: 400 cm2