Relationship between in vivo carcinogenicity and human risk to carbon nanotubes.
Sargent-LM; Porter-DW; Staska-L; Hubbs-AF; Kashon-ML; Lowry-DT; Battelli-LA; Chen-BT; Frazer-DG; Castranova-V; Reynolds-SH
Toxicologist 2014 Mar; 138(1):5
In vitro genotoxicity investigations have shown that high aspect ratio carbon nanotubes induce cell cycle disruption and errors in chromosome number. A subsequent in vivo multiwalled carbon nanotube (MWCNT) whole body inhalation exposure study further demonstrated that MWCNTs promoted the growth of DNA damaged (initiated) lung cells to form lung adenomas and adenocarcinomas. Twenty three percent of the filtered air controls, 27% of the MWCNT-exposed, and 52% of the methylcholanthrene (MCA) followed by air-exposed mice, had a mean of 1.3, 1.3 and 1.4 lung tumors per mouse, respectively. By contrast, 91% of the mice exposed to MCA followed by inhaled MWCNTs (MCA/MWCNT) had an average of 3.24 tumors per mouse. A total of 61 adenocarcinomas and 3 metastatic adenocarcinomas were observed in 55 MCA/MWCNT-treated mice. Furthermore, MWCNT inhalation increased the incidence of serosal tumors consistent with the diagnosis of sarcomatous mesothelioma from 2% in the MCA-exposed mice to 9% in the MCA/MWCNT, a 4.5 fold increase. These data demonstrate that inhaled MWCNTs are strong promoters of pulmonary adenomas and adenocarcinomas in B6C3F1 mice. The presence of metastatic disease in 15% of the MCA/MWCNTexposed mice compared to 1.6% in the MCA-exposed group suggests that carbon nanotubes also induce cancer progression. The mouse MWCNT lung burden in this study approximated feasible human occupational exposures at the NIOSH Recommended Exposure Limit (REL). Given that recent measurements of carbon nanotubes in the workplace indicate levels of nanotubes that can be higher than the NIOSH REL, adverse outcomes in occupationally exposed humans is a possibility. The presentation will include a discussion of the mechanism of MWCNT-induced tumor promotion and progression as well as work in progress to examine the dose response of MWCNT-induced tumor promotion.
Toxicology; Nanotechnology; Pulmonary-disorders; Exposure-levels; Epidemiology; Sampling; Analytical-processes; Chromosome-damage; Chromosome-disorders; Lung; Lung-disease; Lung-function; Cell-function; Cellular-function; Cell-damage; Animals; Laboratory-animals; Cancer; Carcinogens
The Toxicologist. Society of Toxicology 53rd Annual Meeting and ToxExpo, March 23-27, 2014, Phoenix, Arizona