Biomarkers of occupational exposures to carbon nanotubes in humans.
Kagan VE; Khaliullin T; Fatkhutdinova L; Zalyalov R; Tkach A; Murray A; Kisin E; Shvedova A
Toxicologist 2012 Mar; 126(Abstract Suppl):54
Large-scale manufacturing of multiwalled carbon nanotubes (MWCNT) and their wide industrial and biomedical applications raise concerns about potential adverse health effects, especially with respect to pulmonary and systemic outcomes in humans. Of particular importance is the issue of identification of meaningful biomarkers relevant to realistic occupational exposures. We used MWCNT obtained from a manufacturing facility ("NanotechCenter" Ltd., Tambov, Russia) where exposure levels were assessed due to reported excessive exposure of personnel. First, we conducted systematic validation studies using animal and tissue cell models. The dose range was selected based on measured levels of airborne MWCNT at the workplace during various operational procedures (NIOSH 5040 method). Exposure to MWCNT (20-80 microg/mouse) given by pharyngeal aspiration to C57BL/6 mice induced: i) acute inflammation, early granulomatous lesions (7 days) and interstitial fibrosis (28-60 days); ii) increase in biomarkers of inflammation (MPO), pulmonary damage (LDH), fibrosis (TGF-]b, CA125), and oxidative stress (4HNE, protein carbonyls) in bronchoalveolar lavage fluid and serum. Treatment of murine and human airway cells with MWCNT caused dose/time dependent oxidative stress and cytotoxicity. Based on these results - documenting inflammatory and fibrogenic effects of MWCNT - several biomarkers were selected for assessments of health outcomes of exposure to MWCNT. The results of ongoing cross-sectional epidemiological study in which we performed initial assessments of biomarkers of inflammation, early fibrosis and oxidative stress along with psychophysiological tests, cardiovascular and respiratory function assessments in 13 exposed workers are presented.
Nanotechnology; Health-hazards; Immune-system; Immune-reaction; Cell-function; Cellular-reactions; Molecular-biology; Laboratory-testing; Laboratory-animals; Pulmonary-function; Pulmonary-system; Cytotoxic-effects; Lung-cells; Lung-function; Cell-damage; Lung-tissue; Exposure-assessment; Exposure-levels; Analytical-Method; Lung-fibrosis; Biomarkers; Biological-effects; Oxidative-processes; Proteins; Carbonyls; Dose-response; Humans; Employee-exposure;
Author Keywords: Carbon Nanotubes
The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California