Carbon nanotube dosimetry: from workplace exposure assessment to inhalation toxicology.
Dahm-M; Chen-BT; Birch-ME; Evans-DE; Schubauer-Berigan-MK; Hulderman-T; Bilgesu-SA; Leonard-HD; McKinney-W; Frazer-D; Antonini-JM; Porter-DW; Castranova-V; Zeidler-Erdely-PC; Erdely-A
Toxicologist 2013 Mar; 132(1):99
Relevant dosimetry for toxicology studies involving multi-walled carbon nanotubes (MWCNT) has not been well described due to a lack of detailed occupational exposure assessments. In response, exposure assessment findings from U.S.-based MWCNT manufacturers and users were extrapolated to results of an inhalation study in mice. Inhalable and respirable personal breathing zone (PBZ) samples from 9 facilities were collected for the mass concentration of elemental carbon. Upon analysis, 95% of the PBZ samples found exposure concentrations to be <10 microg/m3 with an average inhalable concentration of 8.5 ug/m3. At facilities where respirable and inhalable PBZ samples were collected, respirable samples were approximately 25% of the inhalable size fraction. Using 10 microg/m3, standard worker ventilatory parameters, and assuming 11% alveolar deposition, alveolar deposition was calculated to be 10.56 microg/d. Extrapolation to mouse equivalence by surface area equals 5.2 ng/d. In complement, a 19 d inhalation exposure to MWCNT with daily alveolar depositions of 1250 ng (=240 d of human exposure at 10 microg/m3), 125 ng (=24 d), and 12.5 ng (=2.4 d) was conducted. Mice were sacrificed at day 0, 3, 28, and 84 post-exposure. Pulmonary cytotoxicity (LDH activity) and polymorphonuclear cell (PMN) influx were evident at the high dose through day 84. For the middle dose, no PMN influx was evident and cytotoxicity was significant only at day 0. Lung inflammatory gene expression was increased at the high and middle dose. Alveolar macrophages harvested after exposure and stimulated with LPS showed enhanced cytokine release at the high dose and day 0 for the middle dose. No exposure effects were observed at the lowest dose. These results show a no effect dose lies somewhere in between the middle (=456 d at 10 microg/m3) and low dose (=45.6 d). The findings stress the importance of exposure assessment when extrapolating results of animal MWCNT exposures to potential human outcomes.
Nanotechnology; Microbiology; Microchemistry; Environmental-exposure; Exposure-levels; Physiological-function; Physiological-effects; Physiology; Chemical-properties; Aerosols; Risk-factors; Laboratory-animals; Animals; Neurological-system; Neurological-reactions; Molecular-biology; Molecular-structure; Workers; Toxicology; Dosimetry; Analytical-processes; Risk-analysis
The Toxicologist. Society of Toxicology 52nd Annual Meeting and ToxExpo, March 10-14, 2013, San Antonio, Texas