The inhalation of silica dust in mines, quarries and construction sites causes serious diseases such as silicosis and bronchial cancers. Its toxicity, while proven, hasn’t been well understood – until now. Through a study published in PNAS our researchers are creating a small revolution in knowledge silica dust toxicity, and avenues for neutralising it.
To you the word ‘silica’ may mean nothing but the disease its dust causes is anything but: silicosis. It’s a lung disease caused by the inhalation of crystalline silica dust in mines, quarries, tunnelling and building sites. When not crushed into dust, silica is harmless. You’ll find it, for example, in artificial stone kitchen counters. The natural form of silicon dioxide (SiO2), of which quartz is the best known, is one of the most common minerals in the earth’s crust. ‘It’s everywhere,’ explains Dr Cristina Pavan, a postdoctoral student at the Louvain Centre for Toxicology and Applied Pharmacology (LTAP), directed by Prof. Dominique Lison. ‘It’s in sand, rocks and elsewhere. Throughout the world, several tens of millions of workers are exposed to silica and are likely to suffer from chronic pathologies such as silicosis, but also bronchial cancers, chronic bronchitis, and autoimmune diseases, among others.’ The chemist of Italian origin has just published an article with surprising results in the scientific journal PNAS.
What we know
Much has been written about silica, yet many scientists are still trying to understand it. It’s known, for example, that in its free state, silica exists in two forms: crystalline (e.g. quartz), which is considered the most dangerous, and amorphous (e.g. diatomaceous earth), which is less toxic. It’s also known that silica toxicity is highly variable. Some dusts are more toxic than others, reflecting the multifaceted nature of silicon dioxide. It’s this variability in toxicity that Dr Pavan decided to exploit in order to understand how silica exerts its toxic effect on lungs.
Pure quartz dust by grinding in our laboratories
What happens on the surface?
Until now, silica studies focused mainly on its content and little on how it acts. No one has clarified the interactions that take place on its surface. It’s on this aspect that Dr Pavan has made interesting discoveries. On the surface of silica dust, there’s a series of molecular structures called silanols, composed of Si-OH groups that emerge from dust surface, like short hairs on a scalp. What interested our researcher was the proximity of these structures. ‘Some of them are very close to and interact with each other,’ she explains. ‘Others are more distant and called isolated silanols.’ By clarifying the chemical structures on the surface of silica particles, Dr Pavan discovered that the so-called ‘nearly free silanols’ are the most dangerous. ‘These silanols have energetic properties that make them capable of interacting with cell membranes. They thus induce inflammation, which explains the toxic effect of certain silica dusts.’ She has shown that the physico-chemical characteristics and how silica interacts on the surface determine its toxic activity.
To reach these conclusions, Cristina Pavan was able to rely on the complementary expertise of two European universities: UCLouvain and the University of Turin. Contributing knowledge on the Belgian side were toxicologists, on the Italian side, chemists. And Dr Pavan, with a master’s degree in chemistry and pharmaceutical biology, created the bridges between them: chemists interested in toxicology and toxicologists interested in chemistry. The Turin team characterised the physico-chemical properties of silica dust. To do so, they carried out morphological analyses (size, shape, etc.) and, using infrared spectroscopy, described the mode of interaction of silanols on the surface of silica particles. ‘Infrared light makes it possible to see how the silanols vibrate and therefore how they’re positioned in relation to each other,’ Dr Pavan says. The UCLouvain team carried out biological measurements. ‘We used reactivity tests with model membranes to assess the ability of silica dust to damage cell membranes. To get closer to the lung model, we tested macrophage cells, which are responsible for the inflammatory activity induced by silica, and, finally, evaluated silica’s inflammatory potential.’
Change of perspective
“‘Cristina's study conclusions have changed the perception of silica toxicity,’ says Prof. Lison, the LTAP’s director. ‘Previously it was believed that crystalline silicas were dangerous because they were crystalline and their internal structure made them dangerous. However, Cristina has shown that it’s not this crystalline nature that’s the source of the toxicity. It’s the grinding of crystalline silicas that creates a population of reactive silanols which explains the toxicity. In addition, nearly free silanols also exist on the surface of amorphous silicas, which changes the previous perception that amorphous silicas are necessarily not very toxic because they’re non-crystalline.’
Thinking about tomorrow's silica
Dr Pavan and her team don’t intend to stop at this discovery. ‘We’re already busy understanding how the reactive silanols responsible for toxicity are generated during grinding. Furthermore, we know that the silanols responsible for toxic activity aren’t always stable. We’d like to understand whether atmospheric conditions, such as temperature, could play a role in the industrial storage of silica.’ All this future research has one objective: to find processes that can minimise the danger of silica dust in the workplace. ‘By heating at very high temperatures, 800 degrees, for example, we know that silica loses its nearly free silanols and is less dangerous. But this requires a lot of energy and isn’t industrially profitable for a natural material that initially costs nothing.’ In the end, with a better understanding of reactive surface sites and the silica toxicity process, new industrial applications for silica could also emerge.
A glance at Cristina Pavan's bio
Cristina Pavan is a scientific collaborator with the UCLouvain Institute of Experimental and Clinical Research (IREC), where she has just completed three years of postdoctoral studies at the Louvain Centre for Toxicology and Applied Pharmacology (LTAP) under the supervision of Prof. Dominique Lison. She is now a postdoctoral researcher at the University of Turin (UniTo) Department of Chemistry and the G. Scansetti Interdepartmental Centre for Studies on Asbestos and Other Toxic Particulates. She holds a master’s degree in chemistry and pharmaceutical technologies and a PhD in pharmaceutical and biomolecular sciences, obtained respectively in 2012 and 2016 at the University of Turin. Since her PhD, she has been studying the chemical bases of silica dust toxicity, as part of the close collaboration between the UniTo and UCLouvain teams.