**2. Occupational exposure to coal**

The coal reserves in a worldwide level is up to 847.5 billion of tons, enough amount to serve the current production for 119 years. This prediction is different from the ones related to oil and gas, which have available supplies for less time [11]. According to data from the Interna‐ tional Energy Agency (IEA), coal is the most used resource for energy generation in the world, responsible for 41% of the total production. Nowadays, the main application of mineral coal is to generate energy through thermal power plants. These reserves are considered to have a 109-year lifespan and their coalfields are located in 75 countries. The main world coal pro‐ ducers are China, the United States, India, Australia, Indonesia, Russia, South Africa, Germa‐ ny, Poland, and Kazakhstan, which are responsible for 91% of the world's production [12]. If those projections are right, the consequences of coal mining and combustion will have large effects in the environment. Thus, the exposed populations monitoring is fundamental with the aim of contributing to the state of knowledge about the health risk and motivate the estab‐ lishment of control, hygiene, and prevention strategies.

It is well known that coal mining activities are one of the biggest resources of contamination due to the large quantity of substances liberated in the environment. The content of the coal dust and ashes produced by burning are not always homogeneous and this depends on the source and rank of the coal [13, 14]. Coal dust is constituted from carbon, hydrogen, oxygen, nitrogen, quartz (crystalline silica), and inorganic minerals, such as beryllium, cadmium, cobalt, chromium, iron, boron, copper, nickel, antimony, zinc, aluminum, titanium, magnesi‐ um, manganese, mercury, and lead [15]. As observed, coal is a mixture of a variety of chemicals, including hydrocarbons, which may raise polycyclic aromatic hydrocarbons (PAHs). All technological processes associated with open fire or temperatures between 400 and 600°C, that may lead to PAHs, should be considered potentially hazardous [16, 17].

In relation to coal mining residues exposure, studies in which biomarkers of effect, suscepti‐ bility, and exposure are used as epidemiological tools remain rare and a big part of them come from studies on underground coal mining [18, 19]. The effects generated by open coal mining are little explored, though. In open coal mining, the residues pass directly to the atmosphere, where complex mixtures are formed, and the coal exposure to environmental factors such as sunlight facilitates the processes of spontaneous combustion and, therefore, the release of PAHs [20].

Studies about the coal exposure and its harmful effects have been conducted around the world [21–23]. The main way for exposure of the coal mining workers to the potentially dangerous residues is through the inhaling of coal dust particles from mining and manipulation. It is a known fact that the coal mining continuous exposure can cause a variety of diseases, such as coal workers pneumoconiosis (CWP), silicosis, cancer, and chronic obstructive pulmonary disease (COPD), as emphysema and chronic bronchitis [24].

Many studies have established that some of those diseases could have been originated from the genotoxic damage generated by the inhalation of those mineral particles, able to interact with macrophages, epithelial cells, and other cells generating the production of large amount of reactive oxygen species (ROS) [24–26]. The continuous inhalation of coal dust and fly ashes particles is an important cell and non-cell source of ROS in the lung. This may be associated to the damage of target cells of that tissue and other cell lines, after spreading through the bloodstream [27].

Coal-induced DNA damage is related to macrophage activation and the recruitment of polymorphonuclear cells. This cell activation induces the release of inflammatory mediators, such as cytokines, ROS and reactive nitrogen species (RNS). The proinflammatory properties of ROS and RNS include endothelial cell damage, lipid peroxidation and oxidation, the release of chemostatic factors, the recruitment of neutrophils, and DNA damage [26, 28]. Interaction of ROS with DNA can result in DNA structural and transcriptional errors [29, 30]. Damage caused by ROS is recognized by DNA glycosylases, apurinic/apyrimidinic endonucleases of the base excision repair (BER) mechanism, and in some cases, by the nucleotide excision repair (NER) machinery, leading to DNA strand-breaks [31, 32].

Although chronic exposure may continue to damage the DNA, it has been suggested that inorganic elements can induce DNA single-strand breaks, possibly via the generation of ROS and that this type of damage is soon repaired. Metals are also known to modulate gene expression of enzymes [33]. In addition, PAHs can induce DNA lesions as single-strand breaks via DNA repair mechanisms, related with increased adduct formation and electrophilic metabolites [34–36]. Electrophilic metabolites covalently interact with the DNA [37, 38], and adducts are formed with purines, especially guanine, after metabolic activation by enzymatic complex P450 [39]. The International Agency for Research on Cancer (IARC) classified quartz, main constituent of coal, into IARC Group 1 (carcinogen), due to sufficient evidence for carcinogenicity in experimental animals and in humans [40, 41]. The other factor that could lead to different results in coal dust exposure, with positive and negative results, might be explained by the possible differences in composition, in which the proportion of the metals, PAHs, and silica (quartz) content may have an influence on the genotoxicity. Despite those findings, coal dust remains classified as non-carcinogen for human (Group 3) in IARC [40, 41]. The importance of coal as an energy source makes its characterization and estimation of risks of extreme importance to the safety of those individuals and the environment.

Several factors may explain conflicting results among different studies with human exposed to coal, e.g. cigarettes smoked, age, gender, nutritional status, and individual polymorphisms [6, 42]. Susceptibility is critical to an understanding of coal diseases, including cancer, and many xenobiotic agents act to alter susceptibility. Unknown individual susceptibility, inade‐ quate toxicity data, and the unpredictable nature of interaction effects make the implementa‐ tion of a human biomonitoring assessment for complex mixtures of chemicals extremely complicated.
