Past exposures to dust in coal miners have resulted in the development of pneumoconiosis, with good correlation between dust exposure (concentration), duration and coal workers pneumoconiosis (Attfield and Morring, 1992).
Additionally, King et al (1956) showed a relationship between the severity/grading of diagnosed pneumoconiosis and lung dust burden, i.e. high lung burdens correlated in general with more severe disease. This study found, on average, 35 g of dust in colliers’ lungs.
Stöber et al (1967) reported similarly high dust burdens in the lungs of miners together with extended clearance half-lives. However, overloading of human lungs and reduced clearance rates are not associated with the excessive inflammation and subsequent development of pulmonary tumours which appears to be the typical response of the rat lung to such conditions. This indicates that there are distinct differences in the tissue responses of rat and human lungs to high burdens of low toxicity particulates.
In this context, Nikula et al (1997) compared the anatomical patterns of particle retention and the lung tissue responses between rats and cynomolgus monkeys following chronic exposure to diesel exhaust and coal dust. There was no significant difference between diesel exhaust-exposed monkeys and rats in the relative amount of retained particulate materials but a very important difference was that rats retained a greater portion of the particulate material in the lumina of alveolar ducts and alveoli than monkeys; and monkeys retained a greater portion of the particulate material in the interstitium than rats. Rats, but not monkeys, had significant alveolar epithelial hyperplastic, inflammatory and septal fibrotic responses to the retained particles. The authors concluded that the results suggest that intrapulmonary particle retention patterns and tissue reactions in rats may not be predictive of retention patterns and tissue responses in primates exposed to poorly soluble particles at concentrations representing high occupational exposures. Additionally, they comment that the pulmonary responses of the rats were severe compared to the primate, where the insult to the lungs was handled without adverse consequences (Nikula et al, 1997).
Nikula et al (2001) concluded: ‘these results show that chronically inhaled diesel soot is retained predominantly in the airspaces of rats over a wide range of exposures, whereas in humans, chronically inhaled particulate material is retained primarily in the interstitium. In humans, the percentage of particles in the interstitium is increased with increasing dose (exposure concentration, years of exposure and/or lung burden). This difference in distribution may bring different lung cells into contact with the retained particles or particle-containing macrophages in rats and humans and, therefore, may account for differences in species response to inhaled particles’. These two publications (Nikula et al, 1997, 2001) demonstrate significant species differences in lung responses to inhaled particulates between rats and primates, including humans. They provide some evidence to suggest that not only does the rat differ from other experimental species with respect to the pulmonary response to high doses of low toxicity particulates, but that this difference extends also to primates and humans and there is no reason to consider that TiO2 would be any different (Nikula et al, 2001).
The epidemiology studies investigated whether there was a link between increased incidence of lung cancer and exposure to TiO2 dust. In all the studies the overall conclusion was the same: ‘The results of the studies do not suggest a carcinogenic effect of TiO2 dust on the human lung’ (Hext et al, 2005). This negative finding for lung cancer has been confirmed in other, more recent studies (Ellis et al, 2010, 2013; IARC 2010)
The largely agent-specific lung parenchymal dust diseases (in particular, the pneumoconiosis) were responsible for most of the lung disease mortality and morbidity attributable to occupational exposures in the first half of the century. By the later decades of the century their place had been ceded to disease of the airways, acute and chronic, part of a mid-century epidemic in which tobacco usage was a major environmental cause. Airways disease was broadly defined and included asthma, chronic bronchitis, emphysema, and chronic obstructive pulmonary disease (Becklake, 1998).
The results support four basic mechanisms in the etiology of Coal Workers Pneumoconiosis (CWP) and silicosis:
a) direct cytotoxicity of coal dust or silica, resulting in lung cell damage, release of lipases and proteases, and eventual lung scarring;
b) activation of oxidant production by pulmonary phagocytes, which overwhelms the antioxidant defences and leads to lipid peroxidation, protein nitrosation, cell injury, and lung scarring;
c) activation of mediator release from alveolar macrophages and epithelial cells, which leads to recruitment of poly-morphonuclear leukocytes and macrophages, resulting in the production of pro-inflammatory cytokines and reactive species and in further lung injury and scarring;
d) secretion of growth factors from alveolar macrophages and epithelial cells, stimulating fibroblast proliferation and eventual scarring.
Results of in vitro and animal studies provide a basis for proposing these mechanisms for the initiation and progression of pneumoconiosis. Data obtained from exposed workers lend support to these mechanisms (Castranova and Vallyathan, 2000).
In an epidemiological study in Germany, mortality and cancer morbidity were investigated over the period 1980-2002 (Morfield et al, 2007). In this study, a cohort of coal miners from Saarland (#4579) was analysed regarding mortality and cancer morbidity over the period 1980-2002. Data on causes of death and cancer history was collected form national registers, allocation in dust exposure groups (high or low) was executed by expert judgement and retrospective modelling. The male population of Saarland was used as a control group (Morfield et al, 2007).
With an average work history of 30.4 years in the coal mines, and an average cumulated exposure – between 1400 and 1900 mg/m3 quartz dust times the number of shifts and 16000 to 22000 mg/m3 non-quartz dust times the number of shifts (Morfield et al, 2007).
The health status could be assessed for 99.9% of the cohort population: 1181 deaths (SMR = 0.87; 0.95 interval 0.82-0 92). Cause of death was established in 99.5% of the cohort population: 399 cancer deaths (SMR 0.88; 0.80-0.97) of which 143 lung cancer cases (SMR 0.89; 0.75-1.05). 752 Primary cancer cases were documented (SIR = 0.86; 0.80-0.92), of which 158 lung cancers (SIR =0.92; 0.78-1.08). Lung cancer risks varied with the history of coal miners’ pneumoconiosis; the SMR and SIR ratio is for coal miners approx. 2.5. Exposure modelling did not show any relation with dust exposure. Despite long and high dust exposures no adverse effects of dust exposure could be related with cancer mortality or morbidity. In the analysis effects such as survivor bias, intermediate confounding and dependent censoring were not seen, although the limited number of people in the cohort does limit the complex model analysis. The data of the study are consistent with the scenario that pneumoconiosis acts as a biomarker for lung cancer and not as an exposure marker. A similar association was described for fibrosis (Morfield et al, 2007).
The mortality experience over 22–24 years of 8,899 working coal miners initially medically examined in 1969–1971 at 31 U.S. coal mines was evaluated (Attfield und Kuempel, 2008).
A cohort life-table analysis was undertaken on underlying causes of death, and proportional hazards models were fitted to both underlying, and underlying and contributing causes of death. Elevated mortality from non-violent causes, non-malignant respiratory disease (NMRD), and accidents was observed, but lung cancer and stomach cancer mortality were not elevated. Smoking, pneumoconiosis, coal rank region, and cumulative coal mine dust exposure were all predictors of mortality from nonviolent causes and NMRD. Mortality from nonviolent causes and NMRD was related to dust exposure within the complete cohort and also for the never smoker subgroup. Dust exposure relative risks for mortality were similar for pneumoconiosis, NMRD, and chronic airways obstruction.
In conclusion, the findings from this study show elevations in non-violent cause and NMRD mortality overall and in association with dust exposure, after allowance for age, smoking, and coal rank region. Little definitive evidence was found, however, for any increase in deaths from lung cancer or stomach cancer. A large healthy worker effect appeared to be present, and may have had the effect of attenuating the exposure-response relationships. Mortality was increased with severity of pneumoconiosis as ascertained at start of follow-up. Regional effects, probably associated with coal rank, were very obvious. The results in this study provide additional evidence that exposure to coal mine dust leads to lung diseases other than pneumoconiosis. In particular, the analysis of underlying, and of underlying plus contributing, mortality from chronic airways obstruction shows not only that obstructive airways disease is elevated in coal miners, but also that (1) the risk increases with increasing dust exposure, and (2) manifestation of the disease can occur independently of pneumoconiosis (Attfield und Kuempel, 2008). An interesting review on why there appears to be no increase in lung cancer in coal miners is given by Stayner and Graber (2011)
As an overall conclusion, these more recent studies on the mortality in coalminers seems to support the findings of earlier studies regarding the lack of lung cancer risk, in spite of the presence of inflammatory effects and particle lung overload in this large and well investigated group of workers. This further emphasises the uniqueness of the lung tumours seen in rat lungs under conditions of lung overload caused by exposure to PSPs and their lack of reliability as a predictor to risk to humans from these materials.