Table 3 Overview of key parameters of inhalation studies included in the analysis presented

TiO₂

P25

21

51

1.56 (1.72)

[NO]

6 h/d 5 d/w

for 2 or 4 w

1.5^c, 5.0^c, 15

D3, W4, W26

Measured

Female Sprague-Dawley

13-week

This work

0.40 (1.82)

[NO]

6 h/d 5 d/w

for 4 w

5

D0, D3, W4, W13, W26

Measured

Female Sprague-Dawley

13-week

This work

0.91 (2.19)

[NO]

6 h/d 5 d/w

for 4 w

10

D0, D3, W4, W13, W26

Measured

Male

F344

13-week

Chézeau, et al. [35]

Gate, et al. [36]

0.91 (2.19)

[NO]

6 h/d 5 d/w

for 4 w

10

D0, D3, W4

Measured

Male

F344

19-month

Gate, et al. [36]

Valentino, et al. [52]

1.44 ± 0.57

(2.60 ± 0.38)

[WB]

6 h/d 5 d/w

for 13 w

10

D0, W4, W13, W26, W52

Measured

Female

F344

7-week

Bermudez, et al. [53]

0.7–1.1

(2.3–3.4)

[HO]

6 h/d for 5 d

2, 10, 50

D0, D16

Measured

Male

Wistar

9-week

Ma-Hock, et al. [54]

Fine (anatase)

2100

±1500

8.8

1.0 (2.6)

[WB]

6 h/d for 5 d

50

D7, D14, W4, W9

Measured

Male

F344

180–200 g

Driscoll, et al. [55], Driscoll, et al. [56]

1.2–1.3

(1.9–2.6)

[NO]

6 h/d 5 d/w

for 4 w

0.1, 1, 10

D7

Measured

Female

F344

11–13 weeks

Henderson, et al. [57]

Rutile

pigment

6

1.44 ± 0.09

(1.71 ± 0.23)

[WB]

6 h/d 5 d/w

for 13 w

10, 50, 250

D0, W4, W13, W26, W52

Measured

Female

F344

7-week

Bermudez, et al. [58]

Bayertitan T

(rutile)

1800

1.9

1.1 (1.6)

[NO]

6 h/d 5 d/w

for 13 w

5

D1, W13

Measured

Male & female Wistar

8-week

Morimoto Y., et al. [59]

CB

Printex-90

14

300

0.94 (2.11)

[NO]

6 h/d 5 d/w for 4 w

5^c, 15^c, 50

D3, W4, W26

Measured

Female Sprague-Dawley

13-week

This work

1.4–1.6

(2.4–2.7)

[WB]

6 h/d 5 d/w for 13 w

1.1, 7.6, 50.3

D0, W13, W44

Measured

Female

F344

7-week

Elder, et al. [60]

Gallagher, et al. [61]

0.3–0.5

(2.0–3.2)

[NO]

6 h/d 5 d/w for 4 w

2.9, 9.9, 32.9

D0

Measured

Male

Sprague-Dawley^d

6-week

Lim, et al. [62]

Elftex 12

37

43

2.02–2.42

(1.76–1.90)

[WB]

7 h/d 5 d/w for

12 w

or

16 h/d 7 d/w or 6 h/d 5 d/w or 4 h/d 1 d/w

for 6 or 12 w

3.5, 13.2, 100

D1

or

D0, W12, W24

Measured

Female F344

11–15 weeks

Wolff, et al. [63]

Henderson, et al. [64]

Monarch 880

16

220

0.88

(3.3)

[WB]

6 h/d 5 d/w

for 6.5 w or 13 w

1.1, 7.1, 52.8

D0, W12, W32

Measured

Male

F344

200–250 g

Driscoll, et al. [65]

Sterling V

70

37

0.8

(3.2)

[WB]

6 h/d 5 d/w

for 13 w

48.2

D0, W13, W48

Measured

Female

F344

7-week

Elder, et al. [60]

Gallagher, et al. [61]

MWCNT

MWNT-7

∅ 88 ± 5

L 5.0 ± 4.5

24–28

1.78 (1.69)

[NO]

6 h/d 5 d/w

for 4 w

0.15^c, 0.5^c, 1.5

D3, W4, W26

Measured

Female Sprague-Dawley

13-week

This work

1.2–1.3

(2.4–3.4)

[WB]

6 h/d 5 d/w

for 2 w

0.2, 1, 5

D0

Computed

Male & female F344

6-week

Umeda, et al. [66]

1.4–1.6

(2.3–3.0)

[WB]

6 h/d 5 d/w

for 13 w

0.2, 1, 5

D0

Measured

Male & female F344

6-week

Kasai, et al. [45]

Baytube

(micronized)

∅ 10–15

L 0.30

(0.05–1.35)

210

2.9 (1.9)

[NO]

6 h

11, 241

D7, W13

Measured

Male

Wistar

9-week

Ellinger-Ziegelbauer, et al. [67]

Pauluhn, et al. [68]

255

3.05 (2.0)

[NO]

6 h/d 5 d/w

for 13 w

0.1, 0.4, 1.5, 6

D1, W4, W13, W26

Measured

Male

Wistar

9-week

Pauluhn [46], Pauluhn, et al. [68]

Nikkiso

∅ 44

L Not provided

69

∅: 63 nm (1.5)^e

L: 1.1 mm (2.7)^e

[WB]

6 h/d 5 d/w

for 4 w

0.37

D3, W4, W13

Computed

Male

Wistar

9-week

Morimoto Yasuo, et al. [69]

Oyabu, et al. [70]

NM-401

∅ 67 (24–138)

L 4.0 ± 0.37

18

0.79 (1.83)

[NO]

6 h/d 5 d/w

for 4 w

0.54, 1.49

D3, W4

Measured

Female Sprague-Dawley

13-week

Gate, et al. [14]

Graphistrength

C100

(NM-402)

∅ 12.1

L 1.07 ± 1.10

225.6

1.62–2.03

(2.5–4.7)

[NO]

6 h/d 5 d/w

for 13 w

0.05, 0.25, 5

D1, W13

Computed

Male & female Wistar

8-week

Pothmann, et al. [47]

0.7–2.0

(2.1–4.1)

[HO]

6 h/d 5 d/w

0.15, 0.57, 2.86

D3, D24

Computed

Male & female Wistar

8–9 weeks

Ma-Hock, et al. [71]

NM-403

∅ 12 (5–37)

L 0.40 ± 0.03

135

1.94 (1.48)

[NO]

6 h/d 5 d/w

for 4 w

0.50, 1.48

D3, W4

Computed

Female Sprague-Dawley

13-week

Gate, et al. [14]

JC 162 Incheon

∅ 8–10

L 0.1–0.2

400–600

0.38–1.02

(2.34–3.08)

[NO]

6 h/d 5 d/w

for 4 w

0.26, 1.44, 4.25

D1, D7, W4

Measured

Male Sprague-Dawley

8-week

Kim JK, et al. [72]

Nanocyl

NC 7000

∅ 5–15

L 0.1–10

250–300

0.7–2.0

(2.1–4.1)

[HO]

6 h/d 5 d

2.4, 8.4, 29.8

D3, D23

Computed

Male Wistar

9-week

Ma-Hock, et al. [73]