Table 1.
Studies of mesothelioma in rodents administered MWCNT or SWCNT or other substances.
| Type of CNT, vehicle control, or comparison material | CNT length (μm) | CNT diameter (μm) | CNT catalyst, metal content, treatment | Dose – Mass (mg) | Dose – Fiber number | Mortality (%) during study; mean survival (days) | Mesothelioma proportion (%) | Reference; species, strain, gender; study duration |
|---|---|---|---|---|---|---|---|---|
|
Intraperitoneal
injection (IP), single
| ||||||||
| Vehicle control | na | na | na | 0 | 0 | 2 (739) | 1/50 (2) | Rittinghausen et al. 2014; rat, Wistar, male; 24 mo.§,‡‡‡ |
| MWCNT A (low) | 2.72 ± 2.29† | 0.085 ± 1.60† | Fe | 0.2 | 0.48×109 | 98 (213) | 49/50 (98) | |
| MWCNT A (high) | 8.57 ± 1.51‡ | 1.0 | 2.39×109 | 90 (194) | 45/50 (90) | |||
| MWCNT B (low) | 2.13 ± 2.46† | 0.062 ± 1.71† | Fe | 0.6 | 0.96×109 | 92 (294) | 46/50 (92) | |
| MWCNT B (high) | 9.30 ± 1.63‡ | 3.0 | 4.80×109 | 86 (207) | 45/50 (90) | |||
| MWCNT C (low) | 4.18 ± 2.41† | 0.040 ± 1.57† | Fe | 0.08 | 0.87×109 | 84 (415) | 42/50 (84) | |
| MWCNT C (high) | 10.24 ± 1.64‡ | 0.4 | 4.36×109 | 94 (265) | 47/50 (94) | |||
| MWCNT D (low) | 2.53 ± 2.02† | 0.037 ± 1.45† | Co | 0.05 | 1.51×109 | 40 (666) | 20/50 (40) | |
| MWCNT D (high) | 7.91 ± 1.40‡ | 0.25 | 7.54×109 | 70 (585) | 35/50 (70) | |||
| Amosite asbestos (long) | 6.22 ± 3.12† 13.95 ± 2.10‡ |
3.94 ± 1.83† | na | 1.4 | 0.14×109 | 66 (623) | 33/50 (66) | |
|
IP (half of the total
mass dose was delivered two times in one week)
| ||||||||
| Control | na | na | na | 0 | 0 | 1*** (nr) | 0/23 (0) | Nagai et al. 2011, 2013; rat, F344/Brown Norway F1 hybrid, male & female; 12 mo. |
| MWCNT: NT50a††† (-agg) | Fe, Cu | 2¶¶ | ~3 × 107¶¶ | 40*** | 12/15 (80)* | |||
| NT50a††† (low) | 5.29 ± 0.12 | 0.050 ± 0.0006 | 1 | nr | 70*** | 13/13(100)* | ||
| NT50a††† (high) | 10 | nr | >72*** | 43/43 (100)* | ||||
| NT50b (high) | 4.6 ± 0.1 | 0.052 ± 0.0007 | Fe | 10 | nr | >54*** | 6/6 (100)* | |
| NT145 (low) | 4.6 ± 0.08 | 0.14 ± 0.0016 | none | 1 | ~3 × 107¶¶ | 1*** | 5/29 (17)* | |
| NT145 (high) | 10 | nr | >59*** | 28/30 (93)* | ||||
| NTtngl | nd§§ | nd§§ | Fe | 10 | nr | >60*** | 0/15 (0)¶ | |
|
Intraperitoneal
injection (IP), single
| ||||||||
| Vehicle control (Takagi et al. 2008) | na | na | na | 0 | 0 | 0 | 0/10 (0) | Takagi et al. 2008, 2012; mouse, C57Bl/6, P53+/−, male; 25 to 52 wks |
| Fullerene | nr | nr | nr | 3 | nr | 0 | 0/10 (0) | |
| MWCNT-7 | 1–19 (2 median); 27.5% >5 μm | 0.070–0.170 (0.090 median) | Fe | 0.003 | 1×106|| | 20 (nr) | 5/20 (25)* | |
| 0.03 | 1×107 | 100 | 17/20 (85)* | |||||
| 0.3 | 1×108 | 90 | 19/20 (95)* | |||||
| 3 | 1×109 | 90 | 14/16 (88)*|| | |||||
| Crocidolite (UICC) | 3 | 1×1010 | 50 | 14/18 (78)* | ||||
|
Intraperitoneal
injection (IP), single
| ||||||||
| Vehicle control | na | na | na | 0 | nr f | 60 (nr)†† | 1/26 (3.8) | Muller et al. 2009; rat, Wistar, male; 24 mo. |
| MWCNT (+)** (low) | ~0.7 | 0.011 (±0.0039) | AL, Fe, Co | 2 | 40 | 2/50 (4) | ||
| MWCNT (+) (high) | 20 | 50 | 0/50 (0) | |||||
| MWCNT (−) (high) | 20 | 60 | 3/50 (6) | |||||
| Crocidolite | 2 | 70 | 9/26 (35) | |||||
|
Intraperitoneal
implantation of capsule
| ||||||||
| Crystalline ZnO‡‡ | nr | nr | 0 (all rats survived to end of study) | 0/6 (0) | Varga and Szendi 2010; rat, F344, (nr); 12 mo. | |||
| SWCNT | 4–15 | <0.002 | 90% purity | 10 | 0/6 (0) | |||
| MWCNT | 1–2 | 0.01–0.03 | 98% purity | 10 | 0/6 (0) | |||
|
Intrascrotal
injection, single
| ||||||||
| Vehicle control | na | na | na | 0 | na | 0 | 0/5 (0) | Sakamoto et al. 2009; rat, F344, male |
| MWCNT-7 | 1–4 (2 peak) | 0.070–0.110 (0.090 peak) | Fe (~0.3%) | 0.24 | 8.52×107 | 86 (nr) | 6/7* (86) | |
| Crocidolite | 0.1–5 (1.1–1.2 peak) | 0.03–0.4 (0.11–0.20 peak) | Fe (26–29%) | 0.47 | 1.38×109 | 0 | 0/10 (0) | |
Source: Created for this paper. Some information is the same as in Tables 3.1–3.6 of Monograph 111 (IARC, in press); some additional information is added (e.g., mortality percent); and a new study is added‡‡‡. na: not applicable; nd: not determined; nr: not reported.
Statistically significant (p <0.05).
All fiber sizes.
WHO fiber length (>5 μm length, <3 μm diameter; ≥3:1 length:width ratio).
Fibers >20 μm (% of WHO fibers): 3.81, 9.35, 11.77, 2.13, and 28.55, respectively, for MWCNT A, B, C, and D, and amosite asbestos.
NTtngl: a second group of 6 rats followed for 3 years post-exposure had 0/6 mesothelioma incidence.
Post-exposure duration of 25 wks (vs. 52 wks for other dose groups).
MWCNT(+) denotes material with structural defects; MWCNT(−) denotes material without defects. The authors noted that nanotube numbers were not obtained because agglomeration made counting individual nanotubes unreliable. The authors further noted that the proportion of individual nanotubes >5 μm in length was estimated to be “extremely low.”
No significant difference in survival among groups (p = 0.16).
No vehicle control reported.
Manufacturer reported length 3 μm and diameter 0.015 μm (Table S1, Nagai et al. 2011). All structure sizes in Table 2A for Nagai et al. (2011) are author-reported.
Fiber concentration of NT145 or NT50a(-agg) was ~15 × 103 fibers/μl (Figure 6B of Nagai et al. 2011). Since 2 ml total was injected (i.e., 1 ml, two times in one wk), this would be equal to ~30 × 106 fibers injected of NT145 (at 0.5 mg/ml for 1 mg total) and NTa(-agg) (at 1 mg/ml for 2 mg total).
Calculated from Figure 6(E) of Nagai et al. (2011) for control, NT50a(-agg), NT50a (1 mg) and NT145 (1 mg) based on survival at 350d post-injection. Calculated from Table S2 in Nagai et al. (2011) for the 10 mg dose groups of NT50a, NT50b, NT145, and NTtngl, which is based on survival within several days (~half of the rats in these groups died within several days); the survival is not reported for the 10 mg group at 350 d post-exposure, but it is assumed that the mortality % is greater than that at several days post-injection.
NTa is the same as MWCNT-7.
Study published after the IARC monograph 111 meeting.