Abstract
Inhalation studies are the gold standard for the estimation of the harmful effects of respirable chemical substances, while there is limited evidence of the harmful effects of chemical substances by intratracheal instillation. We reviewed the effectiveness of intratracheal instillation studies for estimating the hazards of nanoparticles, mainly using papers in which both inhalation and intratracheal instillation studies were performed using the same nanoparticles. Compared to inhalation studies, there is a tendency in intratracheal instillation studies that pulmonary inflammation lasted longer in the lungs. A difference in pulmonary inflammation between high and low toxicity nanoparticles was observed in the intratracheal instillation studies, as in the inhalation studies. Among the endpoints of pulmonary toxicity, the kinetics of neutrophil counts, percentage of neutrophils, and chemokines for neutrophils and macrophages, heme oxygenase-1 (HO-1) in bronchoalveolar lavage fluid (BALF), reflected pulmonary inflammation, suggesting that these markers may be considered the predictive markers of pulmonary toxicity in both types of study. When comparing pulmonary inflammation between intratracheal instillation and inhalation studies under the same initial lung burden, there is a tendency that the inflammatory response following the intratracheal instillation of nanoparticles is greater than or equal to that following the inhalation of nanoparticles. If the difference in clearance in both studies is not large, the estimations of pulmonary toxicity are close. We suggest that intratracheal instillation studies can be useful for ranking the hazard of nanoparticles through pulmonary inflammation.
Highlights
In the rapid progress in nanotechnology, the development of new nanoparticle materials based on metals or carbon has advanced
Proinflammatory cytokines and the cytokine-induced neutrophil chemoattractant (CINC) families, including macrophage inflammatory protein-2 (MIP-2), chemokine for neutrophil and macrophages, are reported to be related to pulmonary inflammation induced by inhaled chemicals in both approaches
We reviewed the effectiveness of intratracheal instillation studies for the estimation of the hazard of nanoparticles
Summary
In the rapid progress in nanotechnology, the development of new nanoparticle materials based on metals or carbon has advanced. The gold standard study for estimating the harmful effects of respirable chemical substances is inhalaton studies, which give us extremely important information about the pulmonary toxicity of respirable chemical substances because the physiological exposure route is similar to that in humans [1]. We review the similarities and differences in the data on the pulmonary toxicity of nanoparticles between inhalation and intratracheal instillation studies, and give suggestions on how to avoid the discrepancies in data between the two types of studies. We mainly reviewed references in which both inhalation and intratracheal instillation studies were performed using the same nanoparticles (Table 1), and reviewed the similarities and differences in the data on the pulmonary toxicity (Table 2). The papers in which animals were used have shown documentation of animal protection
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