ArticleACS nano2016
Repetitive Dosing of Fumed Silica Leads to Profibrogenic Effects through Unique Structure-Activity Relationships and Biopersistence in the Lung.
Article in ACS nano, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 72 citations in OpenAlex.
- Long-term SiNPs exposure induced genetic instability and malignant transformation via SQSTM1/p62-mediated autophagy dysfunction in lungs.Materials today. Bio · 2025Article
- From Inflammasomes to Pyroptosis: Molecular Mechanisms in Chronic Intestinal Diseases - Opportunity or Challenge?Journal of inflammation research · 2025Review
- Evaluation of a non-animal toolbox informed by adverse outcome pathways for human inhalation safety.Frontiers in toxicology · 2025Article
- Short- and long-term pathologic responses to quartz are induced by nearly free silanols formed during crystal fracturing.Particle and fibre toxicology · 2024Article
- Pulmonary inflammation and viral replication define distinct clinical outcomes in fatal cases of COVID-19.PLoS pathogens · 2024Article
- Exploiting Mass Spectrometry to Unlock the Mechanism of Nanoparticle-Induced Inflammasome Activation.ACS nano · 2023Article
- Human dendritic cell maturation induced by amorphous silica nanoparticles is Syk-dependent and triggered by lipid raft aggregation.Particle and fibre toxicology · 2023Article
- Cu-doped TiOJournal of nanobiotechnology · 2023Article
- About the Transient Effects of Synthetic Amorphous Silica: An In Vitro Study on Macrophages.International journal of molecular sciences · 2022Article
- Diverse Pathways of Engineered Nanoparticle-Induced NLRP3 Inflammasome Activation.Nanomaterials (Basel, Switzerland) · 2022Review
- Molecular recognition between membrane epitopes and nearly free surface silanols explains silica membranolytic activity.Colloids and surfaces. B, Biointerfaces · 2022Article
- CeONano today · 2022Article
- Pyroptosis: Mechanisms and Links with Fibrosis.Cells · 2021Review
- Advances in Nanomaterials Used in Co-Delivery of siRNA and Small Molecule Drugs for Cancer Treatment.Nanomaterials (Basel, Switzerland) · 2021Review
- The acidified drinking water-induced changes in the behavior and gut microbiota of wild-type mice depend on the acidification mode.Scientific reports · 2021Article
- Nearly free surface silanols are the critical molecular moieties that initiate the toxicity of silica particles.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- How Reversible Are the Effects of Fumed Silica on Macrophages? A Proteomics-Informed View.Nanomaterials (Basel, Switzerland) · 2020Article
- Toxicity to RAW264.7 Macrophages of Silica Nanoparticles and the E551 Food Additive, in Combination with Genotoxic Agents.Nanomaterials (Basel, Switzerland) · 2020Article
- Mechanistic Differences in Cell Death Responses to Metal-Based Engineered Nanomaterials in Kupffer Cells and Hepatocytes.Small (Weinheim an der Bergstrasse, Germany) · 2020Article
- Changes in motor behavior, neuropathology, and gut microbiota of a Batten disease mouse model following administration of acidified drinking water.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 3 countries.
Funding
Abstract
Contrary to the notion that the use of fumed silica in consumer products can "generally (be) regarded as safe" (GRAS), the high surface reactivity of pyrogenic silica differs from other forms of synthetic amorphous silica (SAS), including the capacity to induce membrane damage and acute proinflammatory changes in the murine lung. In addition, the chain-like structure and reactive surface silanols also allow fumed silica to activate the NLRP3 inflammasome, leading to IL-1β production. This pathway is known to be associated with subchronic inflammation and profibrogenic effects in the lung by α-quartz and carbon nanotubes. However, different from the latter materials, bolus dose instillation of 21 mg/kg fumed silica did not induce sustained IL-1β production or subchronic pulmonary effects. In contrast, the NLRP3 inflammasome pathway was continuously activated by repetitive-dose administration of 3 × 7 mg/kg fumed silica, 1 week apart. We also found that while single-dose exposure failed to induce profibrotic effects in the lung, repetitive dosing can trigger increased collagen production, even at 3 × 3 mg/kg. The change between bolus and repetitive dosing was due to a change in lung clearance, with recurrent dosing leading to fumed silica biopersistence, sustained macrophage recruitment, and activation of the NLRP3 pathway. These subchronic proinflammatory effects disappeared when less surface-reactive titanium-doped fumed silica was used for recurrent administration. All considered, these data indicate that while fumed silica may be regarded as safe for some applications, we should reconsider the GRAS label during repetitive or chronic inhalation exposure conditions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.