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The State of the Science: Human Health, Toxicology, and Nanotechnology Risks
Published in Jo Anne Shatkin, Nanotechnology, 2017
For inhalation studies, there are three categories of exposures that are considered. They are: nose only, head, and whole-body exposures. However, there are some adaptations to these types of studies that have been reported in CNT studies. They include delivery into the lungs by intratracheal instillation or pharyngeal aspiration, which are ways of delivering a dose to the lung via the upper airways. While inhalation is considered the most physiologically relevant exposure pathway because it provides a natural route of entry into the lungs and addresses important factors that may influence dose to the subject, instillation and pharyngeal aspiration have been more useful, as the quantitation of dose is better controlled for these methods as opposed to inhalation exposures.
The effect of nanoparticles on pulmonary fibrosis: a systematic review and Meta-analysis of preclinical studies
Published in Archives of Environmental & Occupational Health, 2022
Rana Shahabi, Mohsen Dehghani, Seyed Ali Javad Moosavi, Bahareh Shahabi, Omid Poordakan, Masoumeh Sadeghi, Leila Aryan, Alireza Ghasempoor, Fatemeh Aghanasiri, Mojdeh Mohseni, Bita Mehravi
In confirming this, Shvsedova et al., (2008) showed that inhalation of SWCNT increased TGF- 1 release in BAL fluid at day 7 more than aspiration exposures of SWCNT. Tissue evaluation also revealed that pharyngeal aspiration of SWCNT significantly caused less collagen accumulation and alveolar thickness compared to SWCNT inhalation.13 It seems that the distribution of inhaled nanoparticles is different from the distribution of instilled nanoparticles within the respiratory tract. Another study argued that silica nanoparticles (SNs) could bring about pulmonary damages, such as lung inflammation, alveolar injury, granuloma nodules formation, collagen deposition in the lung tissue and extracellular matrix accumulation by inducing increased expression of proinflammatory cytokine TGF-β1, all resulting in pulmonary fibrosis. However, the results of their study demonstrated that fibrogenesis effects by the SNs are milder than that of the micro scale SiO2 particles in the rats as nanoparticles tend to diffuse via the pulmonary interstitial, and easily move to blood circulation and are excreted through the urine, therefore, SNS depletion in the lungs is due to their ultrafine particle size compared to the microscopic particles.13
Characterization of pulmonary responses in mice to asbestos/asbestiform fibers using gene expression profiles
Published in Journal of Toxicology and Environmental Health, Part A, 2018
Naveena Yanamala, Elena R. Kisin, Dmitriy W. Gutkin, Michael R. Shurin, Martin Harper, Anna A. Shvedova
Mice were exposed to asbestos/asbestiform materials including erionite, tremolite asbestos, crocidolite and wollastonite. Suspensions of particles (80 μg/mouse, 50 μl) were administered by pharyngeal aspiration to experimental mice while, corresponding control group received sterile USP grade Ca2+ and Mg2+ free phosphate buffered saline (PBS). The selected dose was based upon our estimated calculations of approximately 8.8 × 107 fibers/mouse (Murray et al. 2012) with >5 μM size comparable to human occupational exposures estimated at 1010 – 1011 fibers during a lifetime (National Research Council (U.S.). Committee on Nonoccupational Health Risks of Asbestiform Fibers 1984). Briefly, after anesthetization with a mixture of ketamine and xylazine (62.5 and 2.5 mg/kg subcutaneous in the abdominal area), the mouse was placed on a board in a near vertical position and the animal’s tongue extended with lined forceps. A suspension of studied materials prepared in USP grade PBS was placed at the base of the tongue, which was held until the suspension was aspirated into the lungs. The mice revived unassisted after approximately 30–40 min. All mice in erionite, tremolite asbestos, crocidolite, and wollastonite-treated experimental and control groups survived this treatment procedure. This technique provided reliable distribution of particles widely disseminated in a peri-bronchiolar pattern within the alveolar region as was reported previously using histopathology (Rao et al. 2003). Animals treated with the particulates or PBS recovered rapidly after anesthesia with no behavioral or negative health outcomes. Mice were sacrificed 1 and 7 days following exposure to assess the inflammatory responses as evidenced by total cell counts and cell differentials, cytokine/chemokine responses, tissue damage assessed by LDH activity test and/or changes in pulmonary gene expression profiles. To further assess how alterations in gene expression profiles at acute/sub-acute phase (e.g., at 7 days) relate to pulmonary outcomes at extended time points of post exposure, additional groups of animals were sacrificed at 7 and 56 days to evaluate histopathological alterations in the lungs. The 7 days post exposure time point, for evaluating gene expression changes, was specifically selected as it is not overwhelmed by initial acute phase responses and fibrosis is not seen yet upon asbestos exposure (Table 3, 7 days).