Editor's Note: ​This article is the third in a series sponsored by the AIHA Risk Assessment Committee. Other articles in the series include “The Miracle Mineral” in the February issue and “The Economics of Risk” in the May issue​.
Far from Vanquished
The Persistence of 
a Preventable Disease
A ​physician recently told a colleague of mine that no one gets silicosis anymore. Exposures have been reduced to levels of no concern, the physician said, so why should anyone in the 21st century care about expoasure to silica? Where is the risk, he wanted to know. As with other vanquished diseases, such as smallpox, we have moved past the need to evaluate and control silica in the workplace. And if you look solely at the death rate for silicosis, you might be tempted to believe the physician is right. Estimates of death from silicosis in the United States have decreased progressively throughout the 20th century to the current level of fewer than 200 per year. But focusing on death from silicosis as the only adverse outcome to silica exposure is no longer tenable. Silicosis is a risk factor for lung cancer, bronchitis, emphysema, chronic obstructive pulmonary disease (COPD), mycobacterial infections (half of which are tuberculosis), renal disease, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and other autoimmune diseases. In addition, when these diseases are present in conjunction with silicosis, people have shorter survival times—that is, increased mortality rates. Far from being vanquished, silicosis is still a major concern: NIOSH estimates that long-term exposures to 0.1 mg/m3 of respirable crystalline silica (RCS) will result in 1 out of 100 workers developing silicosis. SILICOSIS BACKG​ROUND Silicosis is a progressive non-reversible lung disease caused by crystalline silica and associated with increasingly serious loss of lung function. Communication about this disease and the risks of silica exposure is complicated by the presence of several terms that have different meanings but sound similar to the general public. One such term is silicon, the second most abundant element on earth after oxygen. At high temperature, silicon behaves like a metal and conducts electricity. Silicone is a polymeric substance with rubber-like properties. Silicates are minerals, which consist of silicon, oxygen, and a number of different metallic elements. There are about 20 different classes of silicates, which encompass approximately 90 percent of silicon. Silica, consisting of silicon and oxygen, is the focus of this article. It can exist in two different physical lattices: amorphous silica and crystalline silica. Another name for crystalline silica is quartz. Under conditions of high temperature and pressure, cristobalite and tridimite, polymorphs of crystalline silica, may be formed. Crystalline silica is pathogenic when inhaled in particles small enough to reach the alveolar space in the lung, where oxygen is exchanged. Respirable particles are approximately 10 micrometers (µm) or less. These particles are too small to see, but they are often found in conjunction with larger particles (100–200 µm) visible to the human eye. The size of crystalline silica particles is important in the design of control measures because larger particles will settle more quickly than the smaller, respirable ones. Once RCS is introduced into a workplace, these particles may be drawn into the lungs even after visible dust has settled. This is why capturing RCS at its source and preventing re-entrainment is critical. Exposure to lower levels of RCS over longer periods of time results in chronic silicosis. Once silicosis develops, removal from further silica exposure does not stop the progression of the disease. Knowledge of the cellular basis of disease has expanded exponentially with the advent of cell and molecular biology; for more information, see the sidebar on page 30. 

"NIOSH estimates that long-term exposure to 0.1 mg/m3 of respirable crystalline silica wi​ll result in 1 out of 10​0 workers developing silicosis."

NE​W EXPO​SURES Changing technologies have exposed workers to RCS in novel ways. For example, thousands of Turkish garment workers have developed silicosis, and at least 50 have died, since the 1990s because of exposure to RCS while sand-blasting denim jeans. The hazard could have been anticipated, evaluated, and controlled if people knowledgeable about occupational risk were engaged in the design of the workplace before the work began. More recently, in the U.S., almost half of workers monitored by NIOSH while handling sand on hydrofracking sites had exposures greater than the current OSHA PEL for respirable dust containing crystalline silica. The distinction between occupational and environmental exposure, particularly in the developing world, is often blurred. For example, brick factories in south Asia and east Africa have high levels of RCS. Workers and their families live at the brick factories. The highest exposure levels are in the work area, but RCS dust pervades the entire facility, exposing young children as well as adults. This exposure is more or less continuous, with no recovery time. The epidemiological studies on which exposure limits are based were conducted on groups of workers who did not live at the workplace and who presumably were not exposed to RCS 24 hours a day. In developed countries, workplaces with poor dust control make it possible for workers to track RCS into their vehicles and into their homes on shoes and clothing. Contaminated vehicles can expose the driver and passengers to significant levels of RCS, while contaminated carpets can expose the inhabitants of a home, placing small children, who spend significant time on the floor, at the greatest risk.

"Once respirable crystalline silica is introduced into a workplace, these particles may be drawn into the lungs even after visible dust has settled."

RISK ASSESSMENT Critical to risk assessment is the measurement of dose or its surrogate, exposure. The few dose-response animal studies that have been conducted with RCS suggest significant differences between species. Exposure limits for RCS are based on analysis of large epidemiological studies and meta-studies. A weakness of older studies is that worker health evaluation ceased when workers left employment. We now know that silicosis and silica-related diseases continue to progress throughout the life of exposed individuals. More recent meta-studies have included data from exposed workers throughout retirement until death. These longer studies are important not only because the prevalence of silicosis increases as exposed individuals age but also because the cause of death on death certificates doesn’t always accurately reflect associated morbidity. ​Although silicosis is the most prominent disease associated with silica, the main driver of exposure limits in recent risk assessments is the development of lung cancer. Many studies were used to identify an exposure-response relationship between lung cancer and RCS. Studies of industrial sand workers as well as pooled data from a variety of industries from different countries indicate that mortality from lung cancer is significantly increased when exposure levels were 0.065 mg/m3 or higher. ​The International Agency for Research on Cancer (IARC) first recognized crystalline silica as a carcinogen in 1987. NIOSH recommended an eight-hour time-weighted average exposure limit of 0.05 mg/m3 for crystalline silica in 2002 to protect against lung cancer, pulmonary tuberculosis, and airway diseases. The current ACGIH eight-hour time-weighted average threshold limit value (TLV) for RCS of 0.025 mg/m3 was approved in 2006 to protect against lung fibrosis and cancer. Globally, exposure limits for RCS are typically 0.1 mg/m3 or less and have been decreasing. The current OSHA permissible exposure limit (PEL) for general industry depends on gravimetric measurement of respirable dust, which is then reduced in proportion to the percentage of crystalline silica in the dust. If this method for general industry is used to evaluate respirable dust that is 100 percent crystalline silica, the PEL would be 0.098 mg/m3. OSHA has proposed a new standard that would reduce the eight-hour time-weighted average PEL for RCS to 0.05 mg/m3. (The current OSHA method for the construction and maritime industries relies on the ​particle-counting method.) ​Although quantitative health risk assessment has been viewed as the gold standard to develop exposure limits since the 1980s, other types of risk assessment are valid and, in some cases, preferable. Risk assessments can follow several methodologies, including the EPA quantitative health risk assessment model; the industrial hygiene model of anticipation, recognition, evaluation, control, and communication; and the safety model, which evaluates the severity of the risk and the likelihood of occurrence. Each of the models has strengths and weaknesses and can be used to address different situations effectively. (A thorough discussion of risk assessment models appears in the 6th edition of Patty’s Industrial Hygiene and Toxicology, published in 2010.)

"Exposures can be controlled through basic methods such as wetting the source of RCS or isolating either the dusty process or the worker performing the dusty job."
CONTROLLING SILI​CA EXPOSURES​ For risks associated with RCS, there is consensus on several items: • RCS exposure is associated with silicosis • lung cancer, tuberculosis, and lung, kidney, and immune disease are associated with and/or exacerbated by exposure to RCS • smoking often acts synergistically with RCS exposure to produce silicosis • silicosis, once established, progresses even in the absence of additional RCS exposure Adverse effects are known to occur at exposure levels in the range of 0.05 to 0.1 mg/m3 of RCS. Lower exposures over extended periods are associated with increased morbidity. These serious risks occur frequently. Nonetheless, silicosis is preventable. Exposures can be controlled through basic methods such as wetting the source of RCS or isolating either the dusty process or the worker performing the dusty job. Unfortunately, many workplaces in the developed world have not implemented effective controls and workers are still at risk. The situation is even worse in the developing world due to lack of water and sporadic electrical power to run ventilation systems. Current knowledge about RCS is sufficient to focus resources on control rather than continuous monitoring at increasingly lower exposure limits. Monitoring should be a tool to demonstrate that controls are working as designed. Even though deaths from silicosis have been dramatically reduced during the past century, RCS is still associated with significant risk of morbidity and increased mortality rates. It is possible to envision a world without silicosis. Our profession should work to make that vision a reality.
SILICA AND L​UNG​ CANCER The association between RCS exposures and lung cancer is confounded by many factors. Two of the most important factors are silicosis and smoking. In addition, lung cancer is not one disease but a variety of diseases depending on the cell type that forms the tumor. In one study of white South African gold miners with pulmonary small cell carcinoma, silicosis did not appear to be a prerequisite for carcinogenesis. The authors ​concluded that increased small cell carcinoma was associated with either RCS or radiation exposures. Other studies report increased lung cancer (cell type not indicated) in silica-exposed workers with radiologically diagnosed opacities—that is, silicosis—but not in workers who do not have radiologically diagnosed silicotic lesions. Whether or not silicosis is a prerequisite for lung cancer to develop is still not clear. A possible cellular mechanism of disease progression is that exposure to RCS stimulates pulmonary macrophages, which in turn stimulate other lung cells such as fibrocytes in the alveolar wall (fibrosis), type I and type II pneumocytes, and various circulating white blood cells. The cells stimulated by the biochemicals released by the macrophages are more likely to escape normal cellular control mechanisms and develop into tumors.
SILICOSIS: MECHANISM AND DIAGNOSIS​ When respirable crystalline silica (RCS) particles enter the alveolar space in the human lung, they are engulfed by alveolar macrophages in an attempt to clear them. But if the lung macrophage system is overwhelmed, an inflammatory response ensues with the local production of a variety of cytokines, which are biochemically active molecules. These cytokines stimulate cell division and proliferation of fibrocytes in the alveolar wall. This leads to thickening of the wall, a condition referred to as pulmonary fibrosis. Pulmonary fibrosis increases the diffusion distance for both oxygen and carbon dioxide and reduces measurements of lung function such as forced expiratory volume in 1 second (FEV1). Exposures to non-specific respirable dusts are associated with occurrence of pulmonary fibrosis, as are COPD, emphysema, and other debilitating lung diseases. Traditionally, silicosis is diagnosed by identification of rounded pulmonary opacities on radiographs consistent with the International Labor Organization (ILO) classification. This practice is still in widespread use. Another widespread diagnostic practice is measuring pulmonary function by evaluating how much air an individual can expel from his lungs (a measurement known as forced vital capacity, or FVC) and how fast it is expelled (FEV1). Other conditions such as smoking, emphysema, and fibrotic lung disease also decrease pulmonary function. Some studies report that silicosis as indicated by ILO classifications 1/0 and 1/1, which signify a relatively low profusion of small opacities in the lung, is not typically associated with decreases in lung functions. More recent studies indicate that decreased lung function occurs in workers exposed to 0.1–0.2 mg/m3 RCS in the absence of silicosis and regardless of smoking habits. Analysis of OSHA exposure data from samples taken between January 2003 and December 2009 indicate 20 percent from general industry, and 25 percent from construction, were greater than the current PEL for RCS.
is an industrial hygienist with ARLS Consultants, Inc., in Manlius, N.Y. She is on the faculty of the SUNY School of Public Health and the board of directors of Workplace Health Without Borders. She can be reached at moreilly@albany.edu or (315) 682-3064.​