Five-day inhalation toxicity study of three types of synthetic amorphous silicas in Wistar rats and post-exposure evaluations for up to 3months

Arts, J.H.E.; Muijser, Hans; Duistermaat, Evert; Junker, K.; Kuper, C. Frieke

doi:10.1016/j.fct.2007.04.001

Cited by 141 publications

(121 citation statements)

References 18 publications

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“…Pulmonary inflammation and PAP increased during the recovery period in rats exposed for 40 and 60 days but not 20 days; fibrosis developed even when exposure was stopped prior to its initial development (Porter et al 2004). Several inhalation studies in rats with various quartz molecules, and with exposure from 5 days to 13 weeks (Absher et al 1989;Arts et al 2007;Baggs, Ferin, and Oberdörster 1997;Driscoll et al 1991;Henderson et al 1995;Vallyathan et al 1995), one 4-week inhalation study in mice (Velan, Kumar, and Cohen 1993), and the 11-week study in guinea pigs mentioned above (Heppleston 1986) did not demonstrate PAP but showed inflammation and fibrosis. With the exception of the guinea pig study, a PAS reaction was not performed.…”

Section: Silicon Dioxide/silica/quartzmentioning

confidence: 99%

“…A large number of investigations with amorphous SiO 2 are available (e.g., Arts et al 2007;Ernst et al 2002;Hemenway et al 1986;Kolling et al 2011;Landsiedel et al 2014;Lee and Kelly 1993;Reuzel et al 1991;Rosenbruch et al 1990). A PAS reaction in lung sections seems to have been carried out in only one of these studies (Ernst et al 2002).…”

Section: Silicon Dioxide/silica/quartzmentioning

confidence: 99%

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Particle-induced Pulmonary Alveolar Proteinosis and Subsequent Inflammation and Fibrosis: A Toxicologic and Pathologic Review

Bomhard¹

2017

Toxicol Pathol

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This review analyzes the published data on cases of pulmonary alveolar proteinosis (PAP) in workers inhaling crystalline aluminum, indium, silicon, and titanium particles and possible sequelae, that is, inflammation and fibrosis, and compares these findings with those from animal experiments. In inhalation studies in rodents using crystalline indium and gallium compounds, pronounced PAP followed by inflammation and fibrosis down to very low concentration ranges have been reported. Crystalline aluminum, silicon, and titanium compounds also induced comparable pulmonary changes in animals, though at higher exposure levels. Laboratory animal species appear to react to the induction of PAP with varying degrees of sensitivity. The sensitivity of humans to environmental causes of PAP seems to be relatively low. Up to now, no cases of PAP, or other pulmonary diseases in humans, have been described for gallium compounds. However, a hazard potential can be assumed based on the results of animal studies. Specific particle properties, responsible for the induction of PAP and its sequelae, have not been identified. This review provides indications that, both in animal studies and in humans, PAP is not often recognized due to the absence of properly directed investigation or is concealed behind other forms of lung pathology.

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Section: Silicon Dioxide/silica/quartzmentioning

confidence: 99%

Section: Silicon Dioxide/silica/quartzmentioning

confidence: 99%

Particle-induced Pulmonary Alveolar Proteinosis and Subsequent Inflammation and Fibrosis: A Toxicologic and Pathologic Review

Bomhard¹

2017

Toxicol Pathol

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“…[18][19][20][21] For this reason, engineers are continuously trying to develop SiNPs which have optimal clearance with low toxicity. 1,2) The surface charge may be one of factors causing cellular toxicity. Some researchers have reported that SiNPs that carry a positive charge are more likely to function as DNA carriers for gene transfection.…”

Section: Discussionmentioning

confidence: 99%

“…Crystalline silica is known to cause adverse health effects such as silicosis, [1][2][3] whereas amorphous silicas, being generally free of crystalline forms, are considered to be less toxic. Consequently, amorphous silicas, in the form of synthetic amorphous silica nanoparticles (SiNPs), are used in the production of various consumer goods, such as whiteware, cement, food additives, electric insulators, toothpaste, and tires.…”

Section: Introductionmentioning

confidence: 99%

A Single Instillation of Amorphous Silica Nanoparticles Induced Inflammatory Responses and Tissue Damage until Day 28 after Exposure

Park

Roh

Kim

et al. 2011

JOURNAL OF HEALTH SCIENCE

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Synthetic amorphous silica nanoparticles (SiNPs) are seeing increased and widespread application in diagnosis, imaging, and drug delivery. In the present study, the inflammatory responses and histopathological changes caused by inflowing of SiNPs into the lung were studied in mice after a single intratracheal instillation. Changes in gene expression were also investigated in lung tissue using microarray analysis. As results, weight gain was significantly decreased in SiNP-treated mice on day 1 and 7 after instillation. The secretion of pro-inflammatory cytokines [interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α] and transforming growth factor (TGF)-β were also increased, and the distribution of cytotoxic T cells, natural killer (NK) cells, and natural killer T (NKT) cells with G1 arrest were increased. Microgranulomatous changes were observed on day 7 and 14. Furthermore, the gene expression was significantly affected on day 7. A total of 331 genes were up-regulated more than 2 fold, and 128 genes were down-regulated more than 2 fold. The secretion of inflammatory related cytokines, histopathological abnormalities, and the severity of gene expression changes decreased in a time-dependent manner. Based on these results, we suggest that SiNPs induce subchronic inflammatory responses and tissue damage in mice after a single intratracheal instillation.

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“…However, in vitro, no translocation of quantum dots across primary rat alveolar epithelial cells was observed (Fazlollahi et al 2011, Geys et al 2009). Silica nanoparticles were able to translocate across monolayers of Calu-3, NCI-H292, and A549 cells in vitro (George et al 2015), but were not detected in tracheobronchial lymph nodes aft er inhalation exposure (Arts et al 2007). However, the silica content was not measured in any other tissue or organ besides the lung and lymph nodes, so there might have been some in vivo translocation to the blood, liver, and other organs.…”

Section: Lung Barriermentioning

confidence: 99%

In vitro assays for hazard identification of nanoparticles

Kloet¹

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Five-day inhalation toxicity study of three types of synthetic amorphous silicas in Wistar rats and post-exposure evaluations for up to 3months

Cited by 141 publications

References 18 publications

Particle-induced Pulmonary Alveolar Proteinosis and Subsequent Inflammation and Fibrosis: A Toxicologic and Pathologic Review

Particle-induced Pulmonary Alveolar Proteinosis and Subsequent Inflammation and Fibrosis: A Toxicologic and Pathologic Review

A Single Instillation of Amorphous Silica Nanoparticles Induced Inflammatory Responses and Tissue Damage until Day 28 after Exposure

In vitro assays for hazard identification of nanoparticles

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